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Sample records for hgps cellular lifespan

  1. The influence of osmotic pressure on the lifespan of cellularly inspired energy-relevant materials

    Science.gov (United States)

    Kapania, Esha; Guillen, Katherine; Freeman, Eric; Philen, Michael

    2014-04-01

    Bimolecular unit cells have recently become a focus for biologically-inspired smart materials. This is largely due their ability to exhibit many of the same properties as the natural cell membrane. In this study, two lipid monolayers formed at a water/oil interface are brought together, creating a lipid bilayer at their interface with each droplet containing a different concentration of ions. This ionic concentration gradient leads to the development of a membrane potential across the bilayer as ions begin to passively diffuse across the membrane at varying rates, providing the proof of concept for energy storage through cellular mechanics. The focus of the study is to determine the influence of osmotic pressure on the lifespan of the lipid bilayer. We hypothesize that the greater osmotic pressure that develops from a greater ionic concentration gradient will prove to have a negative impact on the lifespan of the bilayer membrane, causing it to rupture sooner. This is due to the substantial amount of osmotic swelling that will occur to compensate for the ionic concentration gradient. This study will demonstrate how osmotic pressure will continue to be a limiting factor in the effectiveness and stability of cellularly-inspired energy relevant materials.

  2. p16(INK4a suppression by glucose restriction contributes to human cellular lifespan extension through SIRT1-mediated epigenetic and genetic mechanisms.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Li

    Full Text Available Although caloric restriction (CR has been shown to increase lifespan in various animal models, the mechanisms underlying this phenomenon have not yet been revealed. We developed an in vitro system to mimic CR by reducing glucose concentration in cell growth medium which excludes metabolic factors and allows assessment of the effects of CR at the cellular and molecular level. We monitored cellular proliferation of normal WI-38, IMR-90 and MRC-5 human lung fibroblasts and found that glucose restriction (GR can inhibit cellular senescence and significantly extend cellular lifespan compared with cells receiving normal glucose (NG in the culture medium. Moreover, GR decreased expression of p16(INK4a (p16, a well-known senescence-related gene, in all of the tested cell lines. Over-expressed p16 resulted in early replicative senescence in glucose-restricted cells suggesting a crucial role of p16 regulation in GR-induced cellular lifespan extension. The decreased expression of p16 was partly due to GR-induced chromatin remodeling through effects on histone acetylation and methylation of the p16 promoter. GR resulted in an increased expression of SIRT1, a NAD-dependent histone deacetylase, which has positive correlation with CR-induced longevity. The elevated SIRT1 was accompanied by enhanced activation of the Akt/p70S6K1 signaling pathway in response to GR. Furthermore, knockdown of SIRT1 abolished GR-induced p16 repression as well as Akt/p70S6K1 activation implying that SIRT1 may affect p16 repression through direct deacetylation effects and indirect regulation of Akt/p70S6K1 signaling. Collectively, these results provide new insights into interactions between epigenetic and genetic mechanisms on CR-induced longevity that may contribute to anti-aging approaches and also provide a general molecular model for studying CR in vitro in mammalian systems.

  3. Unlike physical exercise, modified environment increases the lifespan of SOD1G93A mice however both conditions induce cellular changes.

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    Yannick N Gerber

    Full Text Available BACKGROUND: Amyotrophic lateral sclerosis (ALS is characterized by a gradual muscular paralysis resulting from progressive motoneurons death. ALS etiology remains unknown although it has been demonstrated to be a multifactorial disease involving several cellular partners. There is currently no effective treatment. Even if the effect of exercise is under investigation for many years, whether physical exercise is beneficial or harmful is still under debate. METHODS AND FINDINGS: We investigated the effect of three different intensities of running exercises on the survival of SOD1(G93A mice. At the early-symptomatic stage (P60, males were isolated and randomly assigned to 5 conditions: 2 sedentary groups ("sedentary" and "sedentary treadmill" placed on the inert treadmill, and 3 different training intensity groups (5 cm/s, 10 cm/s and 21 cm/s; 15 min/day, 5days/week. We first demonstrated that an appropriate "control" of the environment is of the utmost importance since comparison of the two sedentary groups evidenced an 11.6% increase in survival in the "sedentary treadmill" group. Moreover, we showed by immunohistochemistry that this increased lifespan is accompanied with motoneurons survival and increased glial reactivity in the spinal cord. In a second step, we showed that when compared with the proper control, all three running-based training did not modify lifespan of the animals, but result in motoneurons preservation and changes in glial cells activation. CONCLUSIONS/SIGNIFICANCE: We demonstrate that increase in survival induced by a slight daily modification of the environment is associated with motoneurons preservation and strong glial modifications in the lumbar spinal cord of SOD1(G93A. Using the appropriate control, we then demonstrate that all running intensities have no effect on the survival of ALS mice but induce cellular modifications. Our results highlight the critical importance of the control of the environment in ALS studies

  4. Antisense-Based Progerin Downregulation in HGPS-Like Patients’ Cells

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    Karim Harhouri

    2016-07-01

    Full Text Available Progeroid laminopathies, including Hutchinson-Gilford Progeria Syndrome (HGPS, OMIM #176670, are premature and accelerated aging diseases caused by defects in nuclear A-type Lamins. Most HGPS patients carry a de novo point mutation within exon 11 of the LMNA gene encoding A-type Lamins. This mutation activates a cryptic splice site leading to the deletion of 50 amino acids at its carboxy-terminal domain, resulting in a truncated and permanently farnesylated Prelamin A called Prelamin A Δ50 or Progerin. Some patients carry other LMNA mutations affecting exon 11 splicing and are named “HGPS-like” patients. They also produce Progerin and/or other truncated Prelamin A isoforms (Δ35 and Δ90 at the transcriptional and/or protein level. The results we present show that morpholino antisense oligonucleotides (AON prevent pathogenic LMNA splicing, markedly reducing the accumulation of Progerin and/or other truncated Prelamin A isoforms (Prelamin A Δ35, Prelamin A Δ90 in HGPS-like patients’ cells. Finally, a patient affected with Mandibuloacral Dysplasia type B (MAD-B, carrying a homozygous mutation in ZMPSTE24, encoding an enzyme involved in Prelamin A maturation, leading to accumulation of wild type farnesylated Prelamin A, was also included in this study. These results provide preclinical proof of principle for the use of a personalized antisense approach in HGPS-like and MAD-B patients, who may therefore be eligible for inclusion in a therapeutic trial based on this approach, together with classical HGPS patients.

  5. Childhood Personality, Betrayal Trauma, and Leukocyte Telomere Length in Adulthood: A Lifespan Perspective on Conscientiousness and Betrayal Traumas as Predictors of a Biomarker of Cellular Aging.

    Science.gov (United States)

    Edmonds, Grant W; Hampson, Sarah E; Côté, Hélène C F; Hill, Patrick L; Klest, Bridget

    2016-01-01

    Conscientiousness is associated with longevity. As such, identifying the biological pathways linking personality to mortality is important. This study employs longitudinal data spanning >40 years to test prospective associations with Leukocyte Telomere Length (LTL), a potential marker of cellular aging. Because telomeres shorten over time, and are sensitive to oxidative stress, shorter LTL may reflect cumulative damage associated with negative health behaviors and past stressful events. We investigated childhood conscientiousness as a protective factor, expecting an association with longer LTL in adulthood, possibly reflecting slower LTL shortening. Potential lifespan pathways involving childhood trauma, smoking behaviors, and Body Mass Index (BMI) were explored. Childhood conscientiousness showed a small raw association with LTL (r = .08, p = .04), although this effect did not persist when controlling for age and sex. Despite this lack of a direct effect on LTL, we detected an indirect effect operating jointly through BMI and smoking. Higher rates of childhood betrayal trauma were associated with shorter LTL. Contrary to our hypothesis that conscientiousness would buffer this effect, we found evidence for an interaction with childhood betrayal traumas where the association between childhood betrayal traumas and LTL was larger for those higher on conscientiousness in childhood.

  6. Pluripotent stem cells to model Hutchinson-Gilford progeria syndrome (HGPS): Current trends and future perspectives for drug discovery.

    Science.gov (United States)

    Lo Cicero, Alessandra; Nissan, Xavier

    2015-11-01

    Progeria, or Hutchinson-Gilford progeria syndrome (HGPS), is a rare, fatal genetic disease characterized by an appearance of accelerated aging in children. This syndrome is typically caused by mutations in codon 608 (p.G608G) of the LMNA, leading to the production of a mutated form of lamin A precursor called progerin. In HGPS, progerin accumulates in cells causing progressive molecular defects, including nuclear shape abnormalities, chromatin disorganization, damage to DNA and delays in cell proliferation. Here we report how, over the past five years, pluripotent stem cells have provided new insights into the study of HGPS and opened new original therapeutic perspectives to treat the disease.

  7. Temsirolimus Partially Rescues the Hutchinson-Gilford Progeria Cellular Phenotype

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    Gabriel, Diana; Gordon, Leslie B.

    2016-01-01

    Hutchinson-Gilford syndrome (HGPS, OMIM 176670, a rare premature aging disorder that leads to death at an average age of 14.7 years due to myocardial infarction or stroke, is caused by mutations in the LMNA gene. Lamins help maintain the shape and stability of the nuclear envelope in addition to regulating DNA replication, DNA transcription, proliferation and differentiation. The LMNA mutation results in the deletion of 50 amino acids from the carboxy-terminal region of prelamin A, producing the truncated, farnesylated protein progerin. The accumulation of progerin in HGPS nuclei causes numerous morphological and functional changes that lead to premature cellular senescence. Attempts to reverse this HGPS phenotype have identified rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), as a drug that is able to rescue the HGPS cellular phenotype by promoting autophagy and reducing progerin accumulation. Rapamycin is an obvious candidate for the treatment of HGPS disease but is difficult to utilize clinically. To further assess rapamycin’s efficacy with regard to proteostasis, mitochondrial function and the degree of DNA damage, we tested temsirolimus, a rapamycin analog with a more favorable pharmacokinetic profile than rapamycin. We report that temsirolimus decreases progerin levels, increases proliferation, reduces misshapen nuclei, and partially ameliorates DNA damage, but does not improve proteasome activity or mitochondrial dysfunction. Our findings suggest that future therapeutic strategies should identify new drug combinations and treatment regimens that target all the dysfunctional hallmarks that characterize HGPS cells. PMID:28033363

  8. A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells

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    Lo Cicero, Alessandra; Jaskowiak, Anne-Laure; Egesipe, Anne-Laure; Tournois, Johana; Brinon, Benjamin; Pitrez, Patricia R.; Ferreira, Lino; de Sandre-Giovannoli, Annachiara; Levy, Nicolas; Nissan, Xavier

    2016-01-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare fatal genetic disorder that causes systemic accelerated aging in children. Thanks to the pluripotency and self-renewal properties of induced pluripotent stem cells (iPSC), HGPS iPSC-based modeling opens up the possibility of access to different relevant cell types for pharmacological approaches. In this study, 2800 small molecules were explored using high-throughput screening, looking for compounds that could potentially reduce the alkaline phosphatase activity of HGPS mesenchymal stem cells (MSCs) committed into osteogenic differentiation. Results revealed seven compounds that normalized the osteogenic differentiation process and, among these, all-trans retinoic acid and 13-cis-retinoic acid, that also decreased progerin expression. This study highlights the potential of high-throughput drug screening using HGPS iPS-derived cells, in order to find therapeutic compounds for HGPS and, potentially, for other aging-related disorders. PMID:27739443

  9. Vitamin D receptor signaling improves Hutchinson-Gilford progeria syndrome cellular phenotypes.

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    Kreienkamp, Ray; Croke, Monica; Neumann, Martin A; Bedia-Diaz, Gonzalo; Graziano, Simona; Dusso, Adriana; Dorsett, Dale; Carlberg, Carsten; Gonzalo, Susana

    2016-05-24

    Hutchinson-Gilford Progeria Syndrome (HGPS) is a devastating incurable premature aging disease caused by accumulation of progerin, a toxic lamin A mutant protein. HGPS patient-derived cells exhibit nuclear morphological abnormalities, altered signaling pathways, genomic instability, and premature senescence. Here we uncover new molecular mechanisms contributing to cellular decline in progeria. We demonstrate that HGPS cells reduce expression of vitamin D receptor (VDR) and DNA repair factors BRCA1 and 53BP1 with progerin accumulation, and that reconstituting VDR signaling via 1α,25-dihydroxyvitamin D3 (1,25D) treatment improves HGPS phenotypes, including nuclear morphological abnormalities, DNA repair defects, and premature senescence. Importantly, we discovered that the 1,25D/VDR axis regulates LMNA gene expression, as well as expression of DNA repair factors. 1,25D dramatically reduces progerin production in HGPS cells, while stabilizing BRCA1 and 53BP1, two key factors for genome integrity. Vitamin D/VDR axis emerges as a new target for treatment of HGPS and potentially other lamin-related diseases exhibiting VDR deficiency and genomic instability. Because progerin expression increases with age, maintaining vitamin D/VDR signaling could keep the levels of progerin in check during physiological aging.

  10. Discordant gene expression signatures and related phenotypic differences in lamin A- and A/C-related Hutchinson-Gilford progeria syndrome (HGPS.

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    Martina Plasilova

    Full Text Available Hutchinson-Gilford progeria syndrome (HGPS is a genetic disorder displaying features reminiscent of premature senescence caused by germline mutations in the LMNA gene encoding lamin A and C, essential components of the nuclear lamina. By studying a family with homozygous LMNA mutation (K542N, we showed that HGPS can also be caused by mutations affecting both isoforms, lamin A and C. Here, we aimed to elucidate the molecular mechanisms underlying the pathogenesis in both, lamin A- (sporadic and lamin A and C-related (hereditary HGPS. For this, we performed detailed molecular studies on primary fibroblasts of hetero- and homozygous LMNA K542N mutation carriers, accompanied with clinical examinations related to the molecular findings. By assessing global gene expression we found substantial overlap in altered transcription profiles (13.7%; 90/657 in sporadic and hereditary HGPS, with 83.3% (75/90 concordant and 16.7% (15/90 discordant transcriptional changes. Among the concordant ones we observed down-regulation of TWIST2, whose inactivation in mice and humans leads to loss of subcutaneous fat and dermal appendages, and loss of expression in dermal fibroblasts and periadnexial cells from a LMNA(K542N/K542N patient further confirming its pivotal role in skin development. Among the discordant transcriptional profiles we identified two key mediators of vascular calcification and bone metabolism, ENPP1 and OPG, which offer a molecular explanation for the major phenotypic differences in vascular and bone disease in sporadic and hereditary HGPS. Finally, this study correlates reduced TWIST2 and OPG expression with increased osteocalcin levels, thereby linking altered bone remodeling to energy homeostasis in hereditary HGPS.

  11. Discordant Gene Expression Signatures and Related Phenotypic Differences in Lamin A- and A/C-Related Hutchinson-Gilford Progeria Syndrome (HGPS)

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    Plasilova, Martina; Chattopadhyay, Chandon; Ghosh, Apurba; Wenzel, Friedel; Demougin, Philippe; Noppen, Christoph; Schaub, Nathalie; Szinnai, Gabor; Terracciano, Luigi; Heinimann, Karl

    2011-01-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disorder displaying features reminiscent of premature senescence caused by germline mutations in the LMNA gene encoding lamin A and C, essential components of the nuclear lamina. By studying a family with homozygous LMNA mutation (K542N), we showed that HGPS can also be caused by mutations affecting both isoforms, lamin A and C. Here, we aimed to elucidate the molecular mechanisms underlying the pathogenesis in both, lamin A- (sporadic) and lamin A and C-related (hereditary) HGPS. For this, we performed detailed molecular studies on primary fibroblasts of hetero- and homozygous LMNA K542N mutation carriers, accompanied with clinical examinations related to the molecular findings. By assessing global gene expression we found substantial overlap in altered transcription profiles (13.7%; 90/657) in sporadic and hereditary HGPS, with 83.3% (75/90) concordant and 16.7% (15/90) discordant transcriptional changes. Among the concordant ones we observed down-regulation of TWIST2, whose inactivation in mice and humans leads to loss of subcutaneous fat and dermal appendages, and loss of expression in dermal fibroblasts and periadnexial cells from a LMNAK542N/K542N patient further confirming its pivotal role in skin development. Among the discordant transcriptional profiles we identified two key mediators of vascular calcification and bone metabolism, ENPP1 and OPG, which offer a molecular explanation for the major phenotypic differences in vascular and bone disease in sporadic and hereditary HGPS. Finally, this study correlates reduced TWIST2 and OPG expression with increased osteocalcin levels, thereby linking altered bone remodeling to energy homeostasis in hereditary HGPS. PMID:21738662

  12. Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells.

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    Cao, Kan; Graziotto, John J; Blair, Cecilia D; Mazzulli, Joseph R; Erdos, Michael R; Krainc, Dimitri; Collins, Francis S

    2011-06-29

    Hutchinson-Gilford progeria syndrome (HGPS) is a lethal genetic disorder characterized by premature aging. HGPS is most commonly caused by a de novo single-nucleotide substitution in the lamin A/C gene (LMNA) that partially activates a cryptic splice donor site in exon 11, producing an abnormal lamin A protein termed progerin. Accumulation of progerin in dividing cells adversely affects the integrity of the nuclear scaffold and leads to nuclear blebbing in cultured cells. Progerin is also produced in normal cells, increasing in abundance as senescence approaches. Here, we report the effect of rapamycin, a macrolide antibiotic that has been implicated in slowing cellular and organismal aging, on the cellular phenotypes of HGPS fibroblasts. Treatment with rapamycin abolished nuclear blebbing, delayed the onset of cellular senescence, and enhanced the degradation of progerin in HGPS cells. Rapamycin also decreased the formation of insoluble progerin aggregates and induced clearance through autophagic mechanisms in normal fibroblasts. Our findings suggest an additional mechanism for the beneficial effects of rapamycin on longevity and encourage the hypothesis that rapamycin treatment could provide clinical benefit for children with HGPS.

  13. The Lifespan of Ornaments

    DEFF Research Database (Denmark)

    Munch, Anders V.; Riisberg, Vibeke

    ? In this paper we will look at contemporary use of ornament in different scales and contexts – from fashion textiles and interior objects to architecture. The lifespan of a building is different from that of a fashion dress or a plate, but with the digital era it seems like the concern of appropriateness...

  14. Stress and telomere biology: a lifespan perspective.

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    Shalev, Idan; Entringer, Sonja; Wadhwa, Pathik D; Wolkowitz, Owen M; Puterman, Eli; Lin, Jue; Epel, Elissa S

    2013-09-01

    In the past decade, the growing field of telomere science has opened exciting new avenues for understanding the cellular and molecular substrates of stress and stress-related aging processes over the lifespan. Shorter telomere length is associated with advancing chronological age and also increased disease morbidity and mortality. Emerging studies suggest that stress accelerates the erosion of telomeres from very early in life and possibly even influences the initial (newborn) setting of telomere length. In this review, we highlight recent empirical evidence linking stress and mental illnesses at various times across the lifespan with telomere erosion. We first present findings in the developmental programming of telomere biology linking prenatal stress to newborn and adult telomere length. We then present findings linking exposure to childhood trauma and to certain mental disorders with telomere shortening. Last, we review studies that characterize the relationship between related health-risk behaviors with telomere shortening over the lifespan, and how this process may further buffer the negative effects of stress on telomeres. A better understanding of the mechanisms that govern and regulate telomere biology throughout the lifespan may inform our understanding of etiology and the long-term consequences of stress and mental illnesses on aging processes in diverse populations and settings.

  15. Sex differences and stress across the lifespan

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    Bale, Tracy L; Epperson, C Neill

    2015-01-01

    Sex differences in stress responses can be found at all stages of life and are related to both the organizational and activational effects of gonadal hormones and to genes on the sex chromosomes. As stress dysregulation is the most common feature across neuropsychiatric diseases, sex differences in how these pathways develop and mature may predict sex-specific periods of vulnerability to disruption and increased disease risk or resilience across the lifespan. The aging brain is also at risk to the effects of stress, where the rapid decline of gonadal hormones in women combined with cellular aging processes promote sex biases in stress dysregulation. In this Review, we discuss potential underlying mechanisms driving sex differences in stress responses and their relevance to disease. Although stress is involved in a much broader range of diseases than neuropsychiatric ones, we highlight here this area and its examples across the lifespan. PMID:26404716

  16. Changes in Regenerative Capacity through Lifespan

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    Maximina H. Yun

    2015-10-01

    Full Text Available Most organisms experience changes in regenerative abilities through their lifespan. During aging, numerous tissues exhibit a progressive decline in homeostasis and regeneration that results in tissue degeneration, malfunction and pathology. The mechanisms responsible for this decay are both cell intrinsic, such as cellular senescence, as well as cell-extrinsic, such as changes in the regenerative environment. Understanding how these mechanisms impact on regenerative processes is essential to devise therapeutic approaches to improve tissue regeneration and extend healthspan. This review offers an overview of how regenerative abilities change through lifespan in various organisms, the factors that underlie such changes and the avenues for therapeutic intervention. It focuses on established models of mammalian regeneration as well as on models in which regenerative abilities do not decline with age, as these can deliver valuable insights for our understanding of the interplay between regeneration and aging.

  17. Hormonal Programming Across the Lifespan

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    Tobet, Stuart A; Lara, Hernan E; Lucion, Aldo B; Wilson, Melinda E; Recabarren, Sergio E; Paredes, Alfonso H

    2013-01-01

    Hormones influence countless biological processes across the lifespan, and during developmental sensitive periods hormones have the potential to cause permanent tissue-specific alterations in anatomy and physiology. There are numerous critical periods in development wherein different targets are affected. This review outlines the proceedings of the Hormonal Programming in Development session at the US-South American Workshop in Neuroendocrinology in August 2011. Here we discuss how gonadal hormones impact various biological processes within the brain and gonads during early development and describe the changes that take place in the aging female ovary. At the cellular level, hormonal targets in the brain include neurons, glia, or vasculature. On a genomic/epigenomic level, transcription factor signaling and epigenetic changes alter the expression of hormone receptor genes across development and following ischemic brain insult. In addition, organizational hormone exposure alters epigenetic processes in specific brain nuclei and may be a mediator of sexual differentiation of the neonatal brain. During development of the ovary, exposure to excess gonadal hormones leads to polycystic ovarian syndrome (PCOS). Exposure to excess androgens during fetal development also has a profound effect on the development of the male reproductive system. In addition, increased sympathetic nerve activity and stress during early life have been linked to PCOS symptomology in adulthood. Finally, we describe how age-related decreases in fertility are linked to high levels of nerve growth factor (NGF), which enhances sympathetic nerve activity and alters ovarian function. PMID:22700441

  18. A Reduction in Age-Enhanced Gluconeogenesis Extends Lifespan

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    Hachinohe, Mayumi; Yamane, Midori; Akazawa, Daiki; Ohsawa, Kazuhiro; Ohno, Mayumi; Terashita, Yuzu; Masumoto, Hiroshi

    2013-01-01

    The regulation of energy metabolism, such as calorie restriction (CR), is a major determinant of cellular longevity. Although augmented gluconeogenesis is known to occur in aged yeast cells, the role of enhanced gluconeogenesis in aged cells remains undefined. Here, we show that age-enhanced gluconeogenesis is suppressed by the deletion of the tdh2 gene, which encodes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a protein that is involved in both glycolysis and gluconeogenesis in yeast cells. The deletion of TDH2 restores the chronological lifespan of cells with deletions of both the HST3 and HST4 genes, which encode yeast sirtuins, and represses the activation of gluconeogenesis. Furthermore, the tdh2 gene deletion can extend the replicative lifespan in a CR pathway-dependent manner. These findings demonstrate that the repression of enhanced gluconeogenesis effectively extends the cellular lifespan. PMID:23342062

  19. A reduction in age-enhanced gluconeogenesis extends lifespan.

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    Mayumi Hachinohe

    Full Text Available The regulation of energy metabolism, such as calorie restriction (CR, is a major determinant of cellular longevity. Although augmented gluconeogenesis is known to occur in aged yeast cells, the role of enhanced gluconeogenesis in aged cells remains undefined. Here, we show that age-enhanced gluconeogenesis is suppressed by the deletion of the tdh2 gene, which encodes glyceraldehyde-3-phosphate dehydrogenase (GAPDH, a protein that is involved in both glycolysis and gluconeogenesis in yeast cells. The deletion of TDH2 restores the chronological lifespan of cells with deletions of both the HST3 and HST4 genes, which encode yeast sirtuins, and represses the activation of gluconeogenesis. Furthermore, the tdh2 gene deletion can extend the replicative lifespan in a CR pathway-dependent manner. These findings demonstrate that the repression of enhanced gluconeogenesis effectively extends the cellular lifespan.

  20. Hormonal programming across the lifespan.

    Science.gov (United States)

    Nugent, B M; Tobet, S A; Lara, H E; Lucion, A B; Wilson, M E; Recabarren, S E; Paredes, A H

    2012-07-01

    Hormones influence countless biological processes across an animal's lifespan. Many hormone-mediated events occur within developmental sensitive periods, during which hormones have the potential to cause permanent tissue-specific alterations in anatomy and physiology. There are numerous selective critical periods in development with different targets being affected during different periods. This review outlines the proceedings of the Hormonal Programming in Development session at the US-South American Workshop in Neuroendocrinology in August 2011. Here we discuss how gonadal steroid hormones impact various biological processes within the brain and gonads during early development and describe the changes that take place in the aging female ovary. At the cellular level, hormonal targets in the brain include neurons, glia, or vasculature. On a genomic/epigenomic level, transcription factor signaling and epigenetic changes alter the expression of critical hormone receptor genes across development and following ischemic brain insult. In addition, organizational hormone exposure alters epigenetic processes in specific brain nuclei and may be an important mediator of sexual differentiation of the neonatal brain. Brain targets of hormonal programming, such as the paraventricular nucleus of the hypothalamus, may be critical in influencing the development of peripheral targets, such as the ovary. Exposure to excess hormones can cause abnormalities in the ovary during development leading to polycystic ovarian syndrome (PCOS). Exposure to excess androgens during fetal development also has a profound effect on the development of the male reproductive system. In addition, increased activity of the sympathetic nerve and stress during early life have been linked to PCOS symptomology in adulthood. Finally, we describe how age-related decreases in fertility are linked to high levels of nerve growth factor (NGF), which enhances sympathetic nerve activity and alters ovarian function.

  1. The role of MAP4K3 in lifespan regulation of Caenorhabditiselegans

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Maruf H. [Barshop Institute for Longevity and Aging Studies, Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78240 (United States); Hart, Matthew J., E-mail: HartMJ@uthscsa.edu [Barshop Institute for Longevity and Aging Studies, Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78240 (United States); Rea, Shane L., E-mail: reas3@uthscsa.edu [Barshop Institute for Longevity and Aging Studies, Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78240 (United States)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Inhibition of MAP4K3 by RNAi leads to increased mean lifespan in Caenorhabditis elegans. Black-Right-Pointing-Pointer Mutation in the citron homology domain of MAP4K3 leads to increased mean lifespan. Black-Right-Pointing-Pointer Mutation in the kinase domain of MAP4K3 has no significant effect on mean lifespan. -- Abstract: The TOR pathway is a kinase signaling pathway that regulates cellular growth and proliferation in response to nutrients and growth factors. TOR signaling is also important in lifespan regulation - when this pathway is inhibited, either naturally, by genetic mutation, or by pharmacological means, lifespan is extended. MAP4K3 is a Ser/Thr kinase that has recently been found to be involved in TOR activation. Unexpectedly, the effect of this protein is not mediated via Rheb, the more widely known TOR activation pathway. Given the role of TOR in growth and lifespan control, we looked at how inhibiting MAP4K3 in Caenorhabditiselegans affects lifespan. We used both feeding RNAi and genetic mutants to look at the effect of MAP4K3 deficiency. Our results show a small but significant increase in mean lifespan in MAP4K3 deficient worms. MAP4K3 thus represents a new target in the TOR pathway that can be targeted for pharmacological intervention to control lifespan.

  2. Cisd2 mediates lifespan: is there an interconnection among Ca²⁺ homeostasis, autophagy, and lifespan?

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    Wang, C-H; Kao, C-H; Chen, Y-F; Wei, Y-H; Tsai, T-F

    2014-09-01

    CISD2, an evolutionarily conserved novel gene, plays a crucial role in lifespan control and human disease. Mutations in human CISD2 cause type 2 Wolfram syndrome, a rare neurodegenerative and metabolic disorder associated with a shortened lifespan. Significantly, the CISD2 gene is located within a region on human chromosome 4q where a genetic component for human longevity has been mapped through a comparative genome analysis of centenarian siblings. We created Cisd2 knockout (loss-of-function) and transgenic (gain-of-function) mice to study the role of Cisd2 in development and pathophysiology, and demonstrated that Cisd2 expression affects lifespan in mammals. In the Cisd2 knockout mice, Cisd2 deficiency shortens lifespan and drives a panel of premature aging phenotypes. Additionally, an age-dependent decrease of Cisd2 expression has been detected during normal aging in mice. Interestingly, in the Cisd2 transgenic mice, we demonstrated that a persistent level of Cisd2 expression over the different stages of life gives the mice a long-lived phenotype that is linked to an extension in healthy lifespan and a delay in age-associated diseases. At the cellular level, Cisd2 deficiency leads to mitochondrial breakdown and dysfunction accompanied by cell death with autophagic features. Recent studies revealed that Cisd2 may function as an autophagy regulator involved in the Bcl-2 mediated regulation of autophagy. Furthermore, Cisd2 regulates Ca(2+) homeostasis and Ca(2+) has been proposed to have an important regulatory role in autophagy. Finally, it remains to be elucidated if and how the regulation in Ca(2+) homeostasis, autophagy and lifespan are interconnected at the molecular, cellular and organism levels.

  3. Transcription factor genes essential for cell proliferation and replicative lifespan in budding yeast

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    Kamei, Yuka; Tai, Akiko; Dakeyama, Shota; Yamamoto, Kaori; Inoue, Yamato; Kishimoto, Yoshifumi; Ohara, Hiroya; Mukai, Yukio, E-mail: y_mukai@nagahama-i-bio.ac.jp

    2015-07-31

    Many of the lifespan-related genes have been identified in eukaryotes ranging from the yeast to human. However, there is limited information available on the longevity genes that are essential for cell proliferation. Here, we investigated whether the essential genes encoding DNA-binding transcription factors modulated the replicative lifespan of Saccharomyces cerevisiae. Heterozygous diploid knockout strains for FHL1, RAP1, REB1, and MCM1 genes showed significantly short lifespan. {sup 1}H-nuclear magnetic resonance analysis indicated a characteristic metabolic profile in the Δfhl1/FHL1 mutant. These results strongly suggest that FHL1 regulates the transcription of lifespan related metabolic genes. Thus, heterozygous knockout strains could be the potential materials for discovering further novel lifespan genes. - Highlights: • Involvement of yeast TF genes essential for cell growth in lifespan was evaluated. • The essential TF genes, FHL1, RAP1, REB1, and MCM1, regulate replicative lifespan. • Heterozygous deletion of FHL1 changes cellular metabolism related to lifespan.

  4. Elevated proteasome capacity extends replicative lifespan in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Undine Kruegel

    2011-09-01

    Full Text Available Aging is characterized by the accumulation of damaged cellular macromolecules caused by declining repair and elimination pathways. An integral component employed by cells to counter toxic protein aggregates is the conserved ubiquitin/proteasome system (UPS. Previous studies have described an age-dependent decline of proteasomal function and increased longevity correlates with sustained proteasome capacity in centenarians and in naked mole rats, a long-lived rodent. Proof for a direct impact of enhanced proteasome function on longevity, however, is still lacking. To determine the importance of proteasome function in yeast aging, we established a method to modulate UPS capacity by manipulating levels of the UPS-related transcription factor Rpn4. While cells lacking RPN4 exhibit a decreased non-adaptable proteasome pool, loss of UBR2, an ubiquitin ligase that regulates Rpn4 turnover, results in elevated Rpn4 levels, which upregulates UPS components. Increased UPS capacity significantly enhances replicative lifespan (RLS and resistance to proteotoxic stress, while reduced UPS capacity has opposing consequences. Despite tight transcriptional co-regulation of the UPS and oxidative detoxification systems, the impact of proteasome capacity on lifespan is independent of the latter, since elimination of Yap1, a key regulator of the oxidative stress response, does not affect lifespan extension of cells with higher proteasome capacity. Moreover, since elevated proteasome capacity results in improved clearance of toxic huntingtin fragments in a yeast model for neurodegenerative diseases, we speculate that the observed lifespan extension originates from prolonged elimination of damaged proteins in old mother cells. Epistasis analyses indicate that proteasome-mediated modulation of lifespan is at least partially distinct from dietary restriction, Tor1, and Sir2. These findings demonstrate that UPS capacity determines yeast RLS by a mechanism that is distinct

  5. SOD isoforms play no role in lifespan in ad lib or dietary restricted conditions, but mutational inactivation of SOD-1 reduces life extension by cold.

    Science.gov (United States)

    Yen, Kelvin; Patel, Harshil B; Lublin, Alex L; Mobbs, Charles V

    2009-03-01

    The free radical theory of aging is one of the most prominent theories of aging and senescence, but has yet to be definitively proven. If free radicals are the cause of senescence, then the cellular anti-oxidant system should play a large role in lifespan determination. Because superoxide dismutase (SOD) plays a central role in detoxifying superoxide radicals, we have examined the effects of mutational inactivation of each isoform of sod on normal lifespan and lifespan extension by dietary restriction (DR) or cold-/hypothermic-induced longevity (CHIL). We find no significant decrease in lifespan for control worms or worms undergoing DR when sod isoforms are knocked-out even though sod mutational inactivation produces hypersensitivity to paraquat. In contrast, sod-1 inactivation significantly reduces lifespan extension by CHIL, suggesting that CHIL requires a specific genetic program beyond simple reduction in metabolic rate. Furthermore, CHIL paradoxically increases lifespan while reducing resistance to oxidative stress, further disassociating oxidative stress resistance and lifespan.

  6. Mitochondrial ROS Produced via Reverse Electron Transport Extend Animal Lifespan.

    Science.gov (United States)

    Scialò, Filippo; Sriram, Ashwin; Fernández-Ayala, Daniel; Gubina, Nina; Lõhmus, Madis; Nelson, Glyn; Logan, Angela; Cooper, Helen M; Navas, Plácido; Enríquez, Jose Antonio; Murphy, Michael P; Sanz, Alberto

    2016-04-12

    Increased production of reactive oxygen species (ROS) has long been considered a cause of aging. However, recent studies have implicated ROS as essential secondary messengers. Here we show that the site of ROS production significantly contributes to their apparent dual nature. We report that ROS increase with age as mitochondrial function deteriorates. However, we also demonstrate that increasing ROS production specifically through respiratory complex I reverse electron transport extends Drosophila lifespan. Reverse electron transport rescued pathogenesis induced by severe oxidative stress, highlighting the importance of the site of ROS production in signaling. Furthermore, preventing ubiquinone reduction, through knockdown of PINK1, shortens lifespan and accelerates aging; phenotypes that are rescued by increasing reverse electron transport. These results illustrate that the source of a ROS signal is vital in determining its effects on cellular physiology and establish that manipulation of ubiquinone redox state is a valid strategy to delay aging.

  7. A Long Noncoding RNA on the Ribosome Is Required for Lifespan Extension

    NARCIS (Netherlands)

    Essers, Paul B.; Nonnekens, Julie; Goos, Yvonne J.; Betist, Marco C.|info:eu-repo/dai/nl/304073202; Viester, Marjon D.; Mossink, Britt; Lansu, Nico; Korswagen, Hendrik C.; Jelier, Rob; Brenkman, Arjan B.; MacInnes, Alyson W.|info:eu-repo/dai/nl/338681388

    2015-01-01

    The biogenesis of ribosomes and their coordination of protein translation consume an enormous amount of cellular energy. As such, it has been established that the inhibition of either process can extend eukaryotic lifespan. Here, we used next-generation sequencing to compare ribosome-associated RNAs

  8. The effect of resveratrol on lifespan depends on both gender and dietary nutrient composition in Drosophila melanogaster.

    Science.gov (United States)

    Wang, Chunxu; Wheeler, Charles T; Alberico, Thomas; Sun, Xiaoping; Seeberger, Jeanne; Laslo, Mara; Spangler, Edward; Kern, Bradley; de Cabo, Rafael; Zou, Sige

    2013-02-01

    Resveratrol, a polyphenolic compound, has been shown to extend lifespan in different organisms. Emerging evidence suggests that the prolongevity effect of resveratrol depends on dietary composition. However, the mechanisms underlying the interaction of resveratrol and dietary nutrients in modulating lifespan remain elusive. Here, we investigated the effect of resveratrol on lifespan of Drosophila melanogaster fed diets differing in the concentrations of sugar, yeast extract, and palmitic acid representing carbohydrate, protein, and fat, respectively. Resveratrol at up to 200 μM in diets did not affect lifespan of wild-type female flies fed a standard, restricted or high sugar-low protein diet, but extended lifespan of females fed a low sugar-high protein diet. Resveratrol at 400 μM extended lifespan of females fed a high-fat diet. Lifespan extension by resveratrol was associated with downregulation of genes in aging-related pathways, including antioxidant peroxiredoxins, insulin-like peptides involved in insulin-like signaling and several downstream genes in Jun-kinase signaling involved in oxidative stress response. Furthermore, resveratrol increased lifespan of superoxide dismutase 1 (sod1) knockdown mutant females fed a standard or high-fat diet. No lifespan extension by resveratrol was observed in wild-type and sod1 knockdown males under the culture conditions in this study. Our results suggest that the gender-specific prolongevity effect of resveratrol is influenced by dietary composition and resveratrol promotes the survival of flies by modulating genetic pathways that can reduce cellular damage. This study reveals the context-dependent effect of resveratrol on lifespan and suggests the importance of dietary nutrients in implementation of effective aging interventions using dietary supplements.

  9. Extension of yeast chronological lifespan by methylamine.

    Directory of Open Access Journals (Sweden)

    Sanjeev Kumar

    Full Text Available BACKGROUND: Chronological aging of yeast cells is commonly used as a model for aging of human post-mitotic cells. The yeast Saccharomyces cerevisiae grown on glucose in the presence of ammonium sulphate is mainly used in yeast aging research. We have analyzed chronological aging of the yeast Hansenula polymorpha grown at conditions that require primary peroxisome metabolism for growth. METHODOLOGY/PRINCIPAL FINDINGS: The chronological lifespan of H. polymorpha is strongly enhanced when cells are grown on methanol or ethanol, metabolized by peroxisome enzymes, relative to growth on glucose that does not require peroxisomes. The short lifespan of H. polymorpha on glucose is mainly due to medium acidification, whereas most likely ROS do not play an important role. Growth of cells on methanol/methylamine instead of methanol/ammonium sulphate resulted in further lifespan enhancement. This was unrelated to medium acidification. We show that oxidation of methylamine by peroxisomal amine oxidase at carbon starvation conditions is responsible for lifespan extension. The methylamine oxidation product formaldehyde is further oxidized resulting in NADH generation, which contributes to increased ATP generation and reduction of ROS levels in the stationary phase. CONCLUSION/SIGNIFICANCE: We conclude that primary peroxisome metabolism enhanced chronological lifespan of H. polymorpha. Moreover, the possibility to generate NADH at carbon starvation conditions by an organic nitrogen source supports further extension of the lifespan of the cell. Consequently, the interpretation of CLS analyses in yeast should include possible effects on the energy status of the cell.

  10. The Pathogenic Mechanisms and Therapeutic Strategies of Hutchinson-Gilford Progeria Syndrome%早老症(HGPS)的发病机制与治疗策略

    Institute of Scientific and Technical Information of China (English)

    曾涛; 刘新光; 周中军

    2007-01-01

    早老症(Hutchinson-Gilford Progeria Syndrome,HGPS)是一种早发而严重的过早老化性疾病.它是由于编码A/C型核纤层蛋白的LMNA基因发生点突变而引起.这个突变激活了基因11号外显子上一个隐蔽的剪接位点,产生了一种被截短了50个氨基酸的A型核纤层蛋白.然而,一个广泛分布于核膜上结构蛋白的突变,如何引起HGPS患者的早老表现,目前还不太清楚.最近研究发现,HGPS患者的细胞核结构与功能发生了各种异常,主要表现在:progerin蓄积与核变形、细胞核机械性质的改变、组蛋白修饰方式与外遗传控制的改变、基因表达调控异常、p53信号传导通路激活和基因组不稳定等方面.目前存在机械应激假说和基因表达失控假说两种假说解释HGPS的发病机制.对于HGPS患者,尚无有效的临床干预措施,但有学者提出了一些治疗策略,如应用法尼基化的抑制剂、反义寡核苷酸和RNA干扰方法.HGPS被认为是研究正常衰老机制的一个模型.对HGPS深入研究将有助于阐明A型核纤层蛋白和核膜的正常生理功能,及其在生理衰老和疾病中的作用.

  11. Regulation of erythrocyte lifespan: do reactive oxygen species set the clock?

    Science.gov (United States)

    Hattangadi, Shilpa M; Lodish, Harvey F

    2007-08-01

    The forkhead box O (Foxo) subfamily of transcription factors regulates expression of genes important for many cellular processes, ranging from initiation of cell cycle arrest and apoptosis to induction of DNA damage repair. Invertebrate Foxo orthologs such as DAF-16 also regulate longevity. Cellular responses inducing resistance to ROS are important for cellular survival and organism lifespan, but until recently, mammalian factors regulating resistance to oxidative stress have not been well characterized. Marinkovic and colleagues demonstrate in this issue of the JCI that Foxo3 is specifically required for induction of proteins that regulate the in vivo oxidative stress response in murine erythrocytes (see the related article beginning on page 2133). Their work offers the interesting hypothesis that in so doing, Foxo3 may regulate the lifespan of red blood cells, and underlies the importance of understanding the direct targets of this transcription factor and its regulation.

  12. The gametic central cell of Arabidopsis determines the lifespan of adjacent accessory cells.

    Science.gov (United States)

    Kägi, Christina; Baumann, Nadine; Nielsen, Nicola; Stierhof, York-Dieter; Gross-Hardt, Rita

    2010-12-21

    Plant germ cells develop in specialized haploid structures, termed gametophytes. The female gametophyte patterns of flowering plants are diverse, with often unknown adaptive value. Here we present the Arabidopsis fiona mutant, which forms a female gametophyte that is structurally and functionally reminiscent of a phylogenetic distant female gametophyte. The respective changes include a modified reproductive behavior of one of the female germ cells (central cell) and an extended lifespan of three adjacent accessory cells (antipodals). FIONA encodes the cysteinyl t-RNA synthetase SYCO ARATH (SYCO), which is expressed and required in the central cell but not in the antipodals, suggesting that antipodal lifespan is controlled by the adjacent gamete. SYCO localizes to the mitochondria, and ultrastructural analysis of mutant central cells revealed that the protein is necessary for mitochondrial cristae integrity. Furthermore, a dominant ATP/ADP translocator caused mitochondrial cristae degeneration and extended antipodal lifespan when expressed in the central cell of wild-type plants. Notably, this construct did not affect antipodal lifespan when expressed in antipodals. Our results thus identify an unexpected noncell autonomous role for mitochondria in the regulation of cellular lifespan and provide a basis for the coordinated development of gametic and nongametic cells.

  13. A lifespan view of anxiety disorders

    Science.gov (United States)

    Lenze, Eric J.; Wetherell, Julie Loebach

    2011-01-01

    Neurodevelopmental changes over the lifespan, from childhood through adulthood into old age, have important implications for the onset, presentation, course, and treatment of anxiety disorders. This article presents data on anxiety disorders as they appear in older adults, as compared with earlier in life. In this article, we focus on aging-related changes in the epidemiology, presentation, and treatment of anxiety disorders. Also, this article describes some of the gaps and limitations in our understanding and suggests research directions that may elucidate the mechanisms of anxiety disorder development later in life. Finally we describe optimal management of anxiety disorders across the lifespan, in “eight simple steps” for practitioners. PMID:22275845

  14. No turnover in lens lipids for the entire human lifespan.

    Science.gov (United States)

    Hughes, Jessica R; Levchenko, Vladimir A; Blanksby, Stephen J; Mitchell, Todd W; Williams, Alan; Truscott, Roger J W

    2015-03-11

    Lipids are critical to cellular function and it is generally accepted that lipid turnover is rapid and dysregulation in turnover results in disease (Dawidowicz 1987; Phillips et al., 2009; Liu et al., 2013). In this study, we present an intriguing counter-example by demonstrating that in the center of the human ocular lens, there is no lipid turnover in fiber cells during the entire human lifespan. This discovery, combined with prior demonstration of pronounced changes in the lens lipid composition over a lifetime (Hughes et al., 2012), suggests that some lipid classes break down in the body over several decades, whereas others are stable. Such substantial changes in lens cell membranes may play a role in the genesis of age-related eye disorders. Whether long-lived lipids are present in other tissues is not yet known, but this may prove to be important in understanding the development of age-related diseases.

  15. A Lifespan Perspective on Embodied Cognition.

    Science.gov (United States)

    Loeffler, Jonna; Raab, Markus; Cañal-Bruland, Rouwen

    2016-01-01

    Since its infancy embodied cognition research has fundamentally changed our understanding of how action, perception, and cognition relate to and interact with each other. Ideas from different schools of thought have led to controversial theories and a unifying framework is still being debated. In this perspective paper, we argue that in order to improve our understanding of embodied cognition and to take significant steps toward a comprehensive framework, a lifespan approach is mandatory. Given that most established theories have been developed and tested in the adult population, which is characterized by relatively robust and stable sensorimotor and cognitive abilities, we deem it questionable whether embodied cognition effects found in this population are representative for different life stages such as childhood or the elderly. In contrast to adulthood, childhood is accompanied by a rapid increase of sensorimotor and cognitive skills, and the old age by a decline of such capacities. Hence, sensorimotor and cognitive capacities, as well as their interactions, are more fragile at both extremes of the lifespan, thereby offering a unique window into the emergence of embodied cognition effects and age-related differences therein. A lifespan approach promises to make a major contribution toward a unifying and comprehensive theory of embodied cognition that is valid across the lifespan and 'gets better with age.'

  16. Incidental Sequence Learning across the Lifespan

    Science.gov (United States)

    Weiermann, Brigitte; Meier, Beat

    2012-01-01

    The purpose of the present study was to investigate incidental sequence learning across the lifespan. We tested 50 children (aged 7-16), 50 young adults (aged 20-30), and 50 older adults (aged >65) with a sequence learning paradigm that involved both a task and a response sequence. After several blocks of practice, all age groups slowed down…

  17. Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Golegaonkar, Sandeep; Tabrez, Syed S; Pandit, Awadhesh; Sethurathinam, Shalini; Jagadeeshaprasad, Mashanipalya G; Bansode, Sneha; Sampathkumar, Srinivasa-Gopalan; Kulkarni, Mahesh J; Mukhopadhyay, Arnab

    2015-06-01

    Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions.

  18. The thioredoxin TRX-1 regulates adult lifespan extension induced by dietary restriction in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Fierro-Gonzalez, Juan Carlos [Karolinska Institute, Center for Biosciences at NOVUM, Department of Biosciences and Nutrition, S-141 83 Huddinge (Sweden); Gonzalez-Barrios, Maria [Centro Andaluz de Biologia del Desarrollo (CABD-CSIC), Departamento de Fisiologia, Anatomia y Biologia Celular, Universidad Pablo de Olavide, E-41013 Sevilla (Spain); Miranda-Vizuete, Antonio, E-mail: amirviz@upo.es [Centro Andaluz de Biologia del Desarrollo (CABD-CSIC), Departamento de Fisiologia, Anatomia y Biologia Celular, Universidad Pablo de Olavide, E-41013 Sevilla (Spain); Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, E-41013 Sevilla (Spain); Swoboda, Peter, E-mail: peter.swoboda@ki.se [Karolinska Institute, Center for Biosciences at NOVUM, Department of Biosciences and Nutrition, S-141 83 Huddinge (Sweden)

    2011-03-18

    Highlights: {yields} First in vivo data for thioredoxin in dietary-restriction-(DR)-induced longevity. {yields} Thioredoxin (trx-1) loss suppresses longevity of eat-2 mutant, a genetic DR model. {yields} trx-1 overexpression extends wild-type longevity, but not that of eat-2 mutant. {yields} Longevity by dietary deprivation (DD), a non-genetic DR model, requires trx-1. {yields} trx-1 expression in ASJ neurons of aging adults is increased in response to DD. -- Abstract: Dietary restriction (DR) is the only environmental intervention known to extend adult lifespan in a wide variety of animal models. However, the genetic and cellular events that mediate the anti-aging programs induced by DR remain elusive. Here, we used the nematode Caenorhabditis elegans to provide the first in vivo evidence that a thioredoxin (TRX-1) regulates adult lifespan extension induced by DR. We found that deletion of the gene trx-1 completely suppressed the lifespan extension caused by mutation of eat-2, a genetic surrogate of DR in the worm. However, trx-1 deletion only partially suppressed the long lifespan caused by mutation of the insulin-like receptor gene daf-2 or by mutation of the sensory cilia gene osm-5. A trx-1::GFP translational fusion expressed from its own promoter in ASJ neurons (Ptrx-1::trx-1::GFP) rescued the trx-1 deletion-mediated suppression of the lifespan extension caused by mutation of eat-2. This rescue was not observed when trx-1::GFP was expressed from the ges-1 promoter in the intestine. In addition, overexpression of Ptrx-1::trx-1::GFP extended lifespan in wild type, but not in eat-2 mutants. trx-1 deletion almost completely suppressed the lifespan extension induced by dietary deprivation (DD), a non-genetic, nutrient-based model of DR in the worm. Moreover, DD upregulated the expression of a trx-1 promoter-driven GFP reporter gene (Ptrx-1::GFP) in ASJ neurons of aging adults, but not that of control Pgpa-9::GFP (which is also expressed in ASJ neurons). We propose

  19. Induction of cytoprotective pathways is central to the extension of lifespan conferred by multiple longevity pathways.

    Directory of Open Access Journals (Sweden)

    David E Shore

    Full Text Available Many genetic and physiological treatments that extend lifespan also confer resistance to a variety of stressors, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of cytoprotective pathways is essential for lifespan extension or merely correlated. Using a panel of GFP-fused stress response genes, we identified the suites of cytoprotective pathways upregulated by 160 gene inactivations known to increase Caenorhabditis elegans longevity, including the mitochondrial UPR (hsp-6, hsp-60, the ER UPR (hsp-4, ROS response (sod-3, gst-4, and xenobiotic detoxification (gst-4. We then screened for other gene inactivations that disrupt the induction of these responses by xenobiotic or genetic triggers, identifying 29 gene inactivations required for cytoprotective gene expression. If cytoprotective responses contribute directly to lifespan extension, inactivation of these genes would be expected to compromise the extension of lifespan conferred by decreased insulin/IGF-1 signaling, caloric restriction, or the inhibition of mitochondrial function. We find that inactivation of 25 of 29 cytoprotection-regulatory genes shortens the extension of longevity normally induced by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction, without disrupting normal longevity nearly as dramatically. These data demonstrate that induction of cytoprotective pathways is central to longevity extension and identify a large set of new genetic components of the pathways that detect cellular damage and couple that detection to downstream cytoprotective effectors.

  20. Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model

    Directory of Open Access Journals (Sweden)

    Virk Bhupinder

    2012-07-01

    Full Text Available Abstract Background Gut microbes influence animal health and thus, are potential targets for interventions that slow aging. Live E. coli provides the nematode worm Caenorhabditis elegans with vital micronutrients, such as folates that cannot be synthesized by animals. However, the microbe also limits C. elegans lifespan. Understanding these interactions may shed light on how intestinal microbes influence mammalian aging. Results Serendipitously, we isolated an E. coli mutant that slows C. elegans aging. We identified the disrupted gene to be aroD, which is required to synthesize aromatic compounds in the microbe. Adding back aromatic compounds to the media revealed that the increased C. elegans lifespan was caused by decreased availability of para-aminobenzoic acid, a precursor to folate. Consistent with this result, inhibition of folate synthesis by sulfamethoxazole, a sulfonamide, led to a dose-dependent increase in C. elegans lifespan. As expected, these treatments caused a decrease in bacterial and worm folate levels, as measured by mass spectrometry of intact folates. The folate cycle is essential for cellular biosynthesis. However, bacterial proliferation and C. elegans growth and reproduction were unaffected under the conditions that increased lifespan. Conclusions In this animal:microbe system, folates are in excess of that required for biosynthesis. This study suggests that microbial folate synthesis is a pharmacologically accessible target to slow animal aging without detrimental effects.

  1. Self-esteem development across the lifespan

    OpenAIRE

    Robins, Richard W.; Trzesniewski, K H

    2005-01-01

    After decades of debate, a consensus is emerging about the way self-esteem develops across the lifespan. On average, self-esteem is relatively high in childhood, drops during adolescence (particularly for girls), rises-gradually throughout adulthood, and then declines sharply in old age. Despite these general age differences, individuals tend to maintain their ordering relative to one another: Individuals who have relatively high self-esteem at one point in time tend to have relatively high s...

  2. The role of cellular senescence during vascular calcification: a key paradigm in aging research.

    Science.gov (United States)

    Mackenzie, N C W; MacRae, V E

    2011-07-01

    Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events. Vascular calcification refers to the deposition of calcium phosphate mineral, most often hydroxyapatite, in arteries. Extensive calcification of the vascular system is a key characteristic of aging. In this article, we outline the mechanisms governing vascular calcification and highlight its association with cellular senescence. This review discusses the molecular mechanisms of cellular senescence and its affect on calcification of vascular cells, the relevance of phosphate regulation and the function of FGF23 and Klotho proteins. The association of vascular calcification and cellular senescence with the rare human aging disorder Hutchison-Gilford Progeria Syndrome (HGPS) is highlighted and the mouse models used to try to determine the underlying pathways are discussed. By understanding the pathways involved in these processes novel drug targets may be elucidated in an effort to reduce the effects of cellular aging as a risk factor in cardiovascular disease.

  3. QUANTIFYING LIFE STYLE IMPACT ON LIFESPAN

    Directory of Open Access Journals (Sweden)

    Antonello Lorenzini

    2012-12-01

    Full Text Available A healthy diet, physical activity and avoiding dangerous habits such as smoking are effective ways of increasing health and lifespan. Although a significant portion of the world's population still suffers from malnutrition, especially children, the most common cause of death in the world today is non-communicable diseases. Overweight and obesity significantly increase the relative risk for the most relevant non communicable diseases: cardiovascular disease, type II diabetes and some cancers. Childhood overweight also seems to increase the likelihood of disease in adulthood through epigenetic mechanisms. This worrisome trend now termed "globesity" will deeply impact society unless preventive strategies are put into effect. Researchers of the basic biology of aging have clearly established that animals with short lifespans live longer when their diet is calorie restricted. Although similar experiments carried on rhesus monkeys, a longer-lived species more closely related to humans, yielded mixed results, overall the available scientific data suggest keeping the body mass index in the "normal" range increases the chances of living a longer, healthier life. This can be successfully achieved both by maintaining a healthy diet and by engaging in physical activity. In this review we will try to quantify the relative impact of life style choices on lifespan.

  4. Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans.

    Directory of Open Access Journals (Sweden)

    Mai-Britt Mosbech

    Full Text Available Ceramide and its metabolites constitute a diverse group of lipids, which play important roles as structural entities of biological membranes as well as regulators of cellular growth, differentiation, and development. The C. elegans genome comprises three ceramide synthase genes; hyl-1, hyl-2, and lagr-1. HYL-1 function is required for synthesis of ceramides and sphingolipids containing very long acyl-chains (≥C24, while HYL-2 is required for synthesis of ceramides and sphingolipids containing shorter acyl-chains (≤C22. Here we show that functional loss of HYL-2 decreases lifespan, while loss of HYL-1 or LAGR-1 does not affect lifespan. We show that loss of HYL-1 and LAGR-1 functions extend lifespan in an autophagy-dependent manner, as knock down of the autophagy-associated gene ATG-12 abolishes hyl-1;lagr-1 longevity. The transcription factors PHA-4/FOXA, DAF-16/FOXO, and SKN-1 are also required for the observed lifespan extension, as well as the increased number of autophagosomes in hyl-1;lagr-1 animals. Both autophagic events and the transcription factors PHA-4/FOXA, DAF-16, and SKN-1 have previously been associated with dietary restriction-induced longevity. Accordingly, we find that hyl-1;lagr-1 animals display reduced feeding, increased resistance to heat, and reduced reproduction. Collectively, our data suggest that specific sphingolipids produced by different ceramide synthases have opposing roles in determination of C. elegans lifespan. We propose that loss of HYL-1 and LAGR-1 result in dietary restriction-induced autophagy and consequently prolonged longevity.

  5. The Natural Variation in Lifespans of Single Yeast Cells Is Related to Variation in Cell Size, Ribosomal Protein, and Division Time.

    Science.gov (United States)

    Janssens, Georges E; Veenhoff, Liesbeth M

    2016-01-01

    There is a large variability in lifespans of individuals even if they are genetically identical and raised under the same environmental conditions. Our recent system wide study of replicative aging in baker's yeast predicts that protein biogenesis is a driver of aging. Here, we address how the natural variation in replicative lifespan within wild-type populations of yeast cells correlates to three biogenesis-related parameters, namely cell size, ribosomal protein Rpl13A-GFP levels, and division times. Imaging wild type yeast cells in microfluidic devices we observe that in all cells and at all ages, the division times as well as the increase in cell size that single yeast undergo while aging negatively correlate to their lifespan. In the longer-lived cells Rpl13A-GFP levels also negatively correlate to lifespan. Interestingly however, at young ages in the population, ribosome concentration was lowest in the cells that increased the most in size and had shorter lifespans. The correlations between these molecular and cellular properties related to biogenesis and lifespan explain a small portion of the variation in lifespans of individual cells, consistent with the highly individual and multifactorial nature of aging.

  6. Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans

    DEFF Research Database (Denmark)

    Mosbech, Mai-Britt; Kruse, Rikke; Harvald, Eva Bang;

    2013-01-01

    Ceramide and its metabolites constitute a diverse group of lipids, which play important roles as structural entities of biological membranes as well as regulators of cellular growth, differentiation, and development. The C. elegans genome comprises three ceramide synthase genes; hyl-1, hyl-2...... that hyl-1;lagr-1 animals display reduced feeding, increased resistance to heat, and reduced reproduction. Collectively, our data suggest that specific sphingolipids produced by different ceramide synthases have opposing roles in determination of C. elegans lifespan. We propose that loss of HYL-1 and LAGR......, and lagr-1. HYL-1 function is required for synthesis of ceramides and sphingolipids containing very long acyl-chains (≥C24), while HYL-2 is required for synthesis of ceramides and sphingolipids containing shorter acyl-chains (≤C22). Here we show that functional loss of HYL-2 decreases lifespan, while loss...

  7. An engineering approach to extending lifespan in C. elegans.

    Directory of Open Access Journals (Sweden)

    Dror Sagi

    Full Text Available We have taken an engineering approach to extending the lifespan of Caenorhabditis elegans. Aging stands out as a complex trait, because events that occur in old animals are not under strong natural selection. As a result, lifespan can be lengthened rationally using bioengineering to modulate gene expression or to add exogenous components. Here, we engineered longer lifespan by expressing genes from zebrafish encoding molecular functions not normally present in worms. Additionally, we extended lifespan by increasing the activity of four endogenous worm aging pathways. Next, we used a modular approach to extend lifespan by combining components. Finally, we used cell- and worm-based assays to analyze changes in cell physiology and as a rapid means to evaluate whether multi-component transgenic lines were likely to have extended longevity. Using engineering to add novel functions and to tune endogenous functions provides a new framework for lifespan extension that goes beyond the constraints of the worm genome.

  8. Sleep, aging, and lifespan in Drosophila

    Directory of Open Access Journals (Sweden)

    Tononi Giulio

    2010-04-01

    Full Text Available Abstract Background Epidemiological studies in humans suggest that a decrease in daily sleep duration is associated with reduced lifespan, but this issue remains controversial. Other studies in humans also show that both sleep quantity and sleep quality decrease with age. Drosophila melanogaster is a useful model to study aging and sleep, and inheriting mutations affecting the potassium current Shaker results in flies that sleep less and have a shorter lifespan. However, whether the link between short sleep and reduced longevity exists also in wild-type flies is unknown. Similarly, it is unknown whether such a link depends on sleep amount per se, rather than on other factors such as waking activity. Also, sleep quality has been shown to decrease in old flies, but it remains unclear whether aging-related sleep fragmentation is a generalized phenomenon. Results We compared 3 short sleeping mutant lines (Hk1, HkY and Hk2 carrying a mutation in Hyperkinetic, which codes for the beta subunit of the Shaker channel, to wild-type siblings throughout their entire lifespan (all flies kept at 20°C. Hk1 and HkY mutants were short sleeping relative to wild-type controls from day 3 after eclosure, and Hk2 flies became short sleepers about two weeks later. All 3 Hk mutant lines had reduced lifespan relative to wild-type flies. Total sleep time showed a trend to increase in all lines with age, but the effect was most pronounced in Hk1 and HkY flies. In both mutant and wild-type lines sleep quality did not decay with age, but the strong preference for sleep at night declined starting in "middle age". Using Cox regression analysis we found that in Hk1 and HkY mutants and their control lines there was a negative relationship between total sleep amount during the first 2 and 4 weeks of age and hazard (individual risk of death, while no association was found in Hk2 flies and their wild-type controls. Hk1 and HkY mutants and their control lines also showed an

  9. Lifespan of a Ceratitis fruit fly increases with higher altitude

    OpenAIRE

    2010-01-01

    Variation in lifespan may be linked to geographic factors. While latitudinal variation in lifespan has been studied for a number of species, altitude variation has received much less attention, particularly in insects. We measured the lifespan of different populations of the Natal fruit fly Ceratitis rosa along an altitudinal cline. For the different populations we first measured the residual longevity of wild flies by captive cohort approach and compared F1 generation from the same populatio...

  10. Epigenetic variation during the adult lifespan

    DEFF Research Database (Denmark)

    Talens, Rudolf P; Christensen, Kaare; Putter, Hein

    2012-01-01

    The accumulation of epigenetic changes was proposed to contribute to the age-related increase in the risk of most common diseases. In this study on 230 monozygotic twin pairs (MZ pairs), aged 18-89 years, we investigated the occurrence of epigenetic changes over the adult lifespan. Using mass......-related increase in methylation variation was generally attributable to unique environmental factors, except for CRH, for which familial factors may play a more important role. In conclusion, sustained epigenetic differences arise from early adulthood to old age and contribute to an increasing discordance of MZ...

  11. Curcumin-mediated lifespan extension in Caenorhabditis elegans.

    Science.gov (United States)

    Liao, Vivian Hsiu-Chuan; Yu, Chan-Wei; Chu, Yu-Ju; Li, Wen-Hsuan; Hsieh, Yi-Chen; Wang, Teng-Ting

    2011-10-01

    Curcumin is the active ingredient in the herbal medicine and dietary spice, turmeric (Curcuma longa). It has a wide range of biological activities, including anti-inflammatory, antioxidant, chemopreventive, and chemotherapeutic activities. We examined the effects of curcumin on the lifespan and aging in Caenorhabditis elegans, and found that it responded to curcumin with an increased lifespan and reduced intracellular reactive oxygen species and lipofuscin during aging. We analyzed factors that might influence lifespan extension by curcumin. We showed that lifespan extension by curcumin in C. elegans is attributed to its antioxidative properties but not its antimicrobial properties. Moreover, we showed that lifespan extension had effects on body size and the pharyngeal pumping rate but not on reproduction. Finally, lifespan tests with selected stress- and lifespan-relevant mutant strains revealed that the lifespan-extending phenotype was absent from the osr-1, sek-1, mek-1, skn-1, unc-43, sir-2.1, and age-1 mutants, whereas curcumin treatment prolonged the lifespan of mev-1 and daf-16 mutants. Our study has unraveled a diversity of modes of action and signaling pathways to longevity and aging with curcumin exposure in vivo.

  12. Obesity and Lifespan Health—Importance of the Fetal Environment

    Directory of Open Access Journals (Sweden)

    Alice F. Tarantal

    2014-04-01

    Full Text Available A marked increase in the frequency of obesity at the population level has resulted in an increasing number of obese women entering pregnancy. The increasing realization of the importance of the fetal environment in relation to chronic disease across the lifespan has focused attention on the role of maternal obesity in fetal development. Previous studies have demonstrated that obesity during adolescence and adulthood can be traced back to fetal and early childhood exposures. This review focuses on factors that contribute to early developmental events, such as epigenetic modifications, the potential for an increase in inflammatory burden, early developmental programming changes such as the variable development of white versus brown adipose tissue, and alterations in organ ontogeny. We hypothesize that these mechanisms promote an unfavorable fetal environment and can have a long-standing impact, with early manifestations of chronic disease that can result in an increased demand for future health care. In order to identify appropriate preventive measures, attention needs to be placed both on reducing maternal obesity as well as understanding the molecular, cellular, and epigenetic mechanisms that may be responsible for the prenatal onset of chronic disease.

  13. Injuries can prolong lifespan in Drosophila melanogaster males

    DEFF Research Database (Denmark)

    Henten, Anne Marie Vestergaard; Loeschcke, Volker; Pedersen, Jørgen Granfeldt

    2016-01-01

    Previous studies have shown that a range of different stresses can increase mean lifespan. Here we investigated the effect of injuries and bacterial inoculation on mean lifespan in lines selected for increased longevity and their controls. The three lines from each selection regime were subjected...

  14. Minority Stress across the Career-Lifespan Trajectory

    Science.gov (United States)

    Dispenza, Franco; Brown, Colton; Chastain, Taylor E.

    2016-01-01

    Sexual minority persons (e.g., lesbian, gay, bisexual, and queer) are likely to encounter "minority stress", such as discrimination, concealment, expectation of rejection, and internalized heterosexism. Minority stress occurs alongside one's lifespan and has considerable implications in the context of the career lifespan trajectory.…

  15. Lifespan extension by suppression of autophagy genes in Caenorhabditis elegans.

    Science.gov (United States)

    Hashimoto, Yasufumi; Ookuma, Sadatsugu; Nishida, Eisuke

    2009-06-01

    Lifespan is regulated by a complex combination of environmental and genetic factors. Autophagy, which is a bulk degradation system of macromolecules and organelles, has an important role in various biological events. In Caenorhabditis elegans, several autophagy genes have been shown to have a role in promoting longevity, but many other autophagy genes have not been examined for their role in the lifespan regulation. Here we have systematically examined the effect of RNAi suppression of 14 autophagy genes on lifespan. While maternal RNAi of autophagy genes in wild-type worms tended to reduce lifespan, maternal RNAi of each of seven autophagy genes in the insulin/IGF-1 receptor daf-2 mutants extended lifespan. Remarkably, RNAi of unc-51/atg-1, bec-1/atg-6 or atg-9, from young adult, i.e. after development, extended lifespan in both wild-type animals and daf-2 mutants, although RNAi of one or two genes shortened it. Moreover, our analysis suggests that the lifespan extension, which is induced by RNAi of unc-51, bec-1 or atg-9 after development, does not require the transcription factor daf-16, the NAD(+)-dependent protein deacetylase sir-2.1 or the genes related to mitochondrial functions. Collectively, our results suggest that autophagy may not always be beneficial to longevity, but may also function to restrict lifespan in C. elegans.

  16. Involvement of Daphnia pulicaria Sir2 in regulating stress response and lifespan.

    Science.gov (United States)

    Schumpert, Charles A; Anderson, Craig; Dudycha, Jeffry L; Patel, Rekha C

    2016-02-01

    The ability to appropriately respond to proteotoxic stimuli is a major determinant of longevity and involves induction of various heat shock response (HSR) genes, which are essential to cope with cellular and organismal insults throughout lifespan. The activity of NAD+-dependent deacetylase Sir2, originally discovered in yeast, is known to be essential for effective HSR and longevity. Our previous work on HSR inDaphnia pulicaria indicated a drastic reduction of the HSR in older organisms. In this report we investigate the role of Sir2 in regulating HSR during the lifespan of D. pulicaria. We cloned Daphnia Sir2 open reading frame (ORF) to characterize the enzyme activity and confirmed that the overall function of Sir2 was conserved in Daphnia. The Sir2 mRNA levels increased while the enzyme activity declined with age and considering that Sir2 activity regulates HSR, this explains the previously observed age-dependent decline in HSR. Finally, we tested the effect of Sir2 knockdown throughout adult life by using our new RNA interference (RNAi) method by feeding. Sir2 knockdown severely reduced both the median lifespan as well as significantly increased mortality following heat shock. Our study provides the first characterization and functional study of Daphnia Sir2.

  17. Sex differences in the genetic architecture of lifespan in a seed beetle: extreme inbreeding extends male lifespan

    DEFF Research Database (Denmark)

    Bilde, T.; Maklakov, Alexei A.; Meisner, Katrine;

    2009-01-01

    -specific responses to inbreeding to study the genetic architecture of lifespan and mortality rates in Callosobruchus maculatus, a seed beetle that shows sexual dimorphism in lifespan. Two independent assays revealed opposing sex-specific responses to inbreeding. The combined data set showed that inbred males live...

  18. Association of progerin-interactive partner proteins with lamina proteins:Mel18 is associated with emerin in HGPS%Progerin作用的伴侣蛋白和核纤层蛋白问的相互作用:在早老症中Mel18与emerin的相互作用

    Institute of Scientific and Technical Information of China (English)

    Wei-na JU; W. Ted BROWN; Nanbert ZHONG

    2009-01-01

    Objective :The Hutchinson-Gilford progeria syndrome (HGPS or progeria) is a childhood disorder with features of premature aging and is caused by mutations in the lamin A gene resulting in the production of an abnormal protein, termed progerin. To investigate the underlying pathogenic mecha-nism, we studied the nuclear co-localization and association of progerin interactive partner proteins (PIPPs) with lamina proteins. Methods:Both wild-type (WT) and progeria fibroblasts were studied by various methods including eonfocal microscopy, immunopreeipitation and Western blot. Results:All PIPPs discovered so-far co-localized with lamin A/C. In addition, the PIPPs were selectively associated with lamina proteins. An increased immunofluorescent staining signal was found for Mel18 in HGPS as com-pared to WT cells. An association of Me118 with emerin was observed in HGPS, but not in WT cells.Conclusion: Based on these findings, we propose that PIPPs, along with associated lamina proteins may form a pathogenic progerin-containing protein complex.

  19. Alteration of ROS Homeostasis and Decreased Lifespan in S. cerevisiae Elicited by Deletion of the Mitochondrial Translocator FLX1

    Directory of Open Access Journals (Sweden)

    Teresa Anna Giancaspero

    2014-01-01

    Full Text Available This paper deals with the control exerted by the mitochondrial translocator FLX1, which catalyzes the movement of the redox cofactor FAD across the mitochondrial membrane, on the efficiency of ATP production, ROS homeostasis, and lifespan of S. cerevisiae. The deletion of the FLX1 gene resulted in respiration-deficient and small-colony phenotype accompanied by a significant ATP shortage and ROS unbalance in glycerol-grown cells. Moreover, the flx1Δ strain showed H2O2 hypersensitivity and decreased lifespan. The impaired biochemical phenotype found in the flx1Δ strain might be justified by an altered expression of the flavoprotein subunit of succinate dehydrogenase, a key enzyme in bioenergetics and cell regulation. A search for possible cis-acting consensus motifs in the regulatory region upstream SDH1-ORF revealed a dozen of upstream motifs that might respond to induced metabolic changes by altering the expression of Flx1p. Among these motifs, two are present in the regulatory region of genes encoding proteins involved in flavin homeostasis. This is the first evidence that the mitochondrial flavin cofactor status is involved in controlling the lifespan of yeasts, maybe by changing the cellular succinate level. This is not the only case in which the homeostasis of redox cofactors underlies complex phenotypical behaviours, as lifespan in yeasts.

  20. Docosahexaenoic Acid and Cognition throughout the Lifespan

    Directory of Open Access Journals (Sweden)

    Michael J. Weiser

    2016-02-01

    Full Text Available Docosahexaenoic acid (DHA is the predominant omega-3 (n-3 polyunsaturated fatty acid (PUFA found in the brain and can affect neurological function by modulating signal transduction pathways, neurotransmission, neurogenesis, myelination, membrane receptor function, synaptic plasticity, neuroinflammation, membrane integrity and membrane organization. DHA is rapidly accumulated in the brain during gestation and early infancy, and the availability of DHA via transfer from maternal stores impacts the degree of DHA incorporation into neural tissues. The consumption of DHA leads to many positive physiological and behavioral effects, including those on cognition. Advanced cognitive function is uniquely human, and the optimal development and aging of cognitive abilities has profound impacts on quality of life, productivity, and advancement of society in general. However, the modern diet typically lacks appreciable amounts of DHA. Therefore, in modern populations, maintaining optimal levels of DHA in the brain throughout the lifespan likely requires obtaining preformed DHA via dietary or supplemental sources. In this review, we examine the role of DHA in optimal cognition during development, adulthood, and aging with a focus on human evidence and putative mechanisms of action.

  1. Caveolar vesicles generate DNA damage and perpetuate cellular aging

    Institute of Scientific and Technical Information of China (English)

    Keith Wheaton

    2011-01-01

    @@ The replicative limit of human fibroblasts has long provided a model to assess the molecular mechanisms underlying cellular aging [1].In culture, fibroblasts which reach the end of their proliferative lifespan acquire profound molecular changes that limit their response to growth factors, and cause permanent exit from the cell cycle [2].

  2. Cellular automata

    CERN Document Server

    Codd, E F

    1968-01-01

    Cellular Automata presents the fundamental principles of homogeneous cellular systems. This book discusses the possibility of biochemical computers with self-reproducing capability.Organized into eight chapters, this book begins with an overview of some theorems dealing with conditions under which universal computation and construction can be exhibited in cellular spaces. This text then presents a design for a machine embedded in a cellular space or a machine that can compute all computable functions and construct a replica of itself in any accessible and sufficiently large region of t

  3. Manganese rescues adverse effects on lifespan and development in Podospora anserina challenged by excess hydrogen peroxide.

    Science.gov (United States)

    Grimm, Carolin; Osiewacz, Heinz D

    2015-03-01

    For biological systems, balancing cellular levels of reactive oxygen species (ROS) is of great importance because ROS are both, essential for cellular signaling and dangerous in causing molecular damage. Cellular ROS abundance is controlled by a delicate network of molecular pathways. Within this network, superoxide dismutases (SODs) are active in disproportion of the superoxide anion leading to the formation of hydrogen peroxide. The fungal aging model Podospora anserina encodes at least three SODs. One of these is the mitochondrial PaSOD3 isoform containing manganese as a cofactor. Previous work resulted in the selection of strains in which PaSod3 is strongly overexpressed. These strains display impairments in growth and lifespan. A computational model suggests a series of events to occur in Sod3 overexpressing strains leading to adverse effects due to elevated hydrogen peroxide levels. In an attempt to validate this model and to obtain more detailed information about the cellular responses involved in ROS balancing, we further investigated the PaSod3 overexpressing strains. Here we show that hydrogen peroxide levels are indeed strongly increased in the mutant strain. Surprisingly, this phenotype can be rescued by the addition of manganese to the growth medium. Strikingly, while we obtained no evidence for an antioxidant effect of manganese, we found that the metal is required for induction of components of the ROS scavenging network and lowers the hydrogen peroxide level of the mutant. A similar effect of manganese on lifespan reversion was obtained in wild-type strains challenged with exogenous hydrogen peroxide. It appears that manganese is limited under high hydrogen peroxide and suggests that a manganese-dependent activity leads to the induction of ROS scavenging components.

  4. Changes in cortical plasticity across the lifespan

    Directory of Open Access Journals (Sweden)

    Catarina eFreitas

    2011-04-01

    Full Text Available Deterioration of motor and cognitive performance with advancing age is well documented, but its cause remains unknown. Animal studies dating back to the late 1970’s reveal that age-associated neurocognitive changes are linked to age-dependent changes in synaptic plasticity, including alterations of long-term potentiation and depression (LTP and LTD. Non-invasive brain stimulation techniques enable measurement of LTP- and LTD-like mechanisms of plasticity, in vivo, in humans, and may thus provide valuable insights. We examined the effects of a 40-second train of continuous theta-burst stimulation (cTBS to the motor cortex (600 stimuli, 3 pulses at 50 Hz applied at a frequency of 5 Hz on cortico-spinal excitability as measured by the motor evoked potentials (MEPs induced by single-pulse TMS before and after cTBS in the contralateral first dorsal interosseus muscle. Thirty-six healthy individuals aged 19 to 81 years old were studied in two sites (Boston, USA and Barcelona, Spain. The findings did not differ across study sites. We found that advancing age is negatively correlated with the duration of the effect of cTBS (r = -0.367; p = 0.028 and the overall amount of corticomotor suppression induced by cTBS (r = -0.478; p = 0.003, and positively correlated with the maximal suppression of amplitude on motor evoked responses in the target muscle (r = 0.420; p = 0.011. We performed magnetic resonance imaging (MRI-based individual morphometric analysis in a subset of subjects to demonstrate that these findings are not explained by age-related brain atrophy or differences in scalp-to-brain distance that could have affected the TBS effects. Our findings provide empirical evidence that the mechanisms of cortical plasticity area are altered with aging and their efficiency decreases across the human lifespan. This may critically contribute to motor and possibly cognitive decline.

  5. Sex differences in the genetic architecture of lifespan in a seed beetle: extreme inbreeding extends male lifespan

    Directory of Open Access Journals (Sweden)

    Maklakov Alexei A

    2009-02-01

    Full Text Available Abstract Background Sex differences in lifespan are ubiquitous throughout the animal kingdom but the causes underlying this phenomenon remain poorly understood. Several explanations based on asymmetrical inheritance patterns (sex chromosomes or mitochondrial DNA have been proposed, but these ideas have rarely been tested experimentally. Alternatively, sexual dimorphism in lifespan could result from sex-specific selection, caused by fundamental differences in how males and females optimize their fitness by allocating resources into current and future reproduction. Results Here we used sex-specific responses to inbreeding to study the genetic architecture of lifespan and mortality rates in Callosobruchus maculatus, a seed beetle that shows sexual dimorphism in lifespan. Two independent assays revealed opposing sex-specific responses to inbreeding. The combined data set showed that inbred males live longer than outbred males, while females show the opposite pattern. Both sexes suffered reduced fitness measured as lifetime reproductive success as a result of inbreeding. Conclusion No model based on asymmetrical inheritance can explain increased male lifespan in response to inbreeding. Our results are however compatible with models based on sex-specific selection on reproductive strategies. We therefore suggest that sex-specific differences in lifespan in this species primarily result from sexually divergent selection.

  6. Evolutionarily Conserved and Nonconserved Cellular Localizations and Functions of Human SIRT Proteins

    OpenAIRE

    Michishita, Eriko; Park, Jean Y.; Burneskis, Jenna M.; Barrett, J. Carl; Horikawa, Izumi

    2005-01-01

    Sir2 is a NAD+-dependent protein deacetylase that extends lifespan in yeast and worms. This study examines seven human proteins homologous to Sir2 (SIRT1 through SIRT7) for cellular localization, expression profiles, protein deacetylation activity, and effects on human cell lifespan. We found that: 1) three nuclear SIRT proteins (SIRT1, SIRT6, and SIRT7) show different subnuclear localizations: SIRT6 and SIRT7 are associated with heterochromatic regions and nucleoli, respectively, where yeast...

  7. Malate and fumarate extend lifespan in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Clare B Edwards

    Full Text Available Malate, the tricarboxylic acid (TCA cycle metabolite, increased lifespan and thermotolerance in the nematode C. elegans. Malate can be synthesized from fumarate by the enzyme fumarase and further oxidized to oxaloacetate by malate dehydrogenase with the accompanying reduction of NAD. Addition of fumarate also extended lifespan, but succinate addition did not, although all three intermediates activated nuclear translocation of the cytoprotective DAF-16/FOXO transcription factor and protected from paraquat-induced oxidative stress. The glyoxylate shunt, an anabolic pathway linked to lifespan extension in C. elegans, reversibly converts isocitrate and acetyl-CoA to succinate, malate, and CoA. The increased longevity provided by malate addition did not occur in fumarase (fum-1, glyoxylate shunt (gei-7, succinate dehydrogenase flavoprotein (sdha-2, or soluble fumarate reductase F48E8.3 RNAi knockdown worms. Therefore, to increase lifespan, malate must be first converted to fumarate, then fumarate must be reduced to succinate by soluble fumarate reductase and the mitochondrial electron transport chain complex II. Reduction of fumarate to succinate is coupled with the oxidation of FADH2 to FAD. Lifespan extension induced by malate depended upon the longevity regulators DAF-16 and SIR-2.1. Malate supplementation did not extend the lifespan of long-lived eat-2 mutant worms, a model of dietary restriction. Malate and fumarate addition increased oxygen consumption, but decreased ATP levels and mitochondrial membrane potential suggesting a mild uncoupling of oxidative phosphorylation. Malate also increased NADPH, NAD, and the NAD/NADH ratio. Fumarate reduction, glyoxylate shunt activity, and mild mitochondrial uncoupling likely contribute to the lifespan extension induced by malate and fumarate by increasing the amount of oxidized NAD and FAD cofactors.

  8. Nucleic acid therapy for lifespan prolongation: Present and future

    Indian Academy of Sciences (India)

    Wing-Fu Lai

    2011-09-01

    Lifespan prolongation is a common desire of the human race. With advances in biotechnology, the mechanism of aging has been gradually unraveled, laying the theoretical basis of nucleic acid therapy for lifespan prolongation. Regretfully, clinically applicable interventions do not exist without the efforts of converting theory into action, and it is the latter that has been far from adequately addressed at the moment. This was demonstrated by a database search on PubMed and Web of Science, from which only seven studies published between 2000 and 2010 were found to directly touch on the development of nucleic acid therapy for anti-aging and/or longevity enhancing purposes. In light of this, the objective of this article is to overview the current understanding of the intimate association between genes and longevity, and to bring the prospect of nucleic acid therapy for lifespan prolongation to light.

  9. The association between intelligence and lifespan is mostly genetic

    DEFF Research Database (Denmark)

    Arden, Rosalind; Luciano, Michelle; Deary, Ian J

    2016-01-01

    differed between the samples. We used three methods of genetic analysis to examine the relationship between intelligence and lifespan: we calculated the proportion of the more intelligent twins who outlived their co-twin; we regressed within-twin-pair lifespan differences on within-twin-pair intelligence......BACKGROUND: Several studies in the new field of cognitive epidemiology have shown that higher intelligence predicts longer lifespan. This positive correlation might arise from socioeconomic status influencing both intelligence and health; intelligence leading to better health behaviours; and....../or some shared genetic factors influencing both intelligence and health. Distinguishing among these hypotheses is crucial for medicine and public health, but can only be accomplished by studying a genetically informative sample. METHODS: We analysed data from three genetically informative samples...

  10. Mechanosensory Neuron Aging: Differential Trajectories with Lifespan-Extending Alaskan Berry and Fungal Treatments in Caenorhabditis elegans

    Science.gov (United States)

    Scerbak, Courtney; Vayndorf, Elena M.; Hernandez, Alicia; McGill, Colin; Taylor, Barbara E.

    2016-01-01

    Many nutritional interventions that increase lifespan are also proposed to postpone age-related declines in motor and cognitive function. Potential sources of anti-aging compounds are the plants and fungi that have adapted to extreme environments. We studied the effects of four commonly consumed and culturally relevant Interior Alaska berry and fungus species (bog blueberry, lowbush cranberry, crowberry, and chaga) on the decline in overall health and neuron function and changes in touch receptor neuron morphology associated with aging. We observed increased wild-type Caenorhabditis elegans lifespan and improved markers of healthspan upon treatment with Alaskan blueberry, lowbush cranberry, and chaga extracts. Interestingly, although all three treatments increased lifespan, they differentially affected the development of aberrant morphologies in touch receptor neurons. Blueberry treatments decreased anterior mechanosensory neuron (ALM) aberrations (i.e., extended outgrowths and abnormal cell bodies) while lowbush cranberry treatment increased posterior mechanosensory neuron (PLM) aberrations, namely process branching. Chaga treatment both decreased ALM aberrations (i.e., extended outgrowths) and increased PLM aberrations (i.e., process branching and loops). These results support the large body of knowledge positing that there are multiple cellular strategies and mechanisms for promoting health with age. Importantly, these results also demonstrate that although an accumulation of abnormal neuron morphologies is associated with aging and decreased health, not all of these morphologies are detrimental to neuronal and organismal health. PMID:27486399

  11. Cellular Telephone

    Institute of Scientific and Technical Information of China (English)

    杨周

    1996-01-01

    Cellular phones, used in automobiles, airliners, and passenger trains, are basically low-power radiotelephones. Calls go through radio transmitters that are located within small geographical units called cells. Because each cell’s signals are too weak to interfere with those of other cells operating on the same fre-

  12. Comparative cellular biogerontology: primer and prospectus.

    Science.gov (United States)

    Miller, Richard A; Williams, Joseph B; Kiklevich, J Veronika; Austad, Steve; Harper, James M

    2011-04-01

    Most prior work on the biological basis of aging has focused on describing differences between young and old individuals but provided only limited insight into the mechanisms controlling the rate of aging. Natural selection has produced a goldmine of experimental material, in the form of species of differing aging rate, whose longevity can vary by 10-fold or more within mammalian orders, but these resources remain largely unexplored at the cellular level. In this review article we focus on one approach to comparative biogerontology: the strategy of evaluating the properties of cultured cells from organisms of varying lifespan and aging rate. In addition, we discuss problems associated with the analysis and interpretations of interspecific variation of cellular trait data among species with disparate longevity. Given the impressive array of 'natural experiments' in aging rate, overcoming the technical and conceptual obstacles confronting research in comparative cellular gerontology will be well worth the effort. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Researching Cognition and Technology: How We Learn across the Lifespan

    Science.gov (United States)

    Petrina, Stephen; Feng, Franc; Kim, Juyun

    2008-01-01

    This article addresses how we learn technology across the lifespan. After outlining findings of research into how children, adolescents, teens and adults learn technology, we address theoretical shifts from sociocultural to technocultural theories of cognition and reorientations from mediated to cyborgenic learning. The balance of the article…

  14. Telomerase activity coevolves with body mass, not lifespan

    Science.gov (United States)

    Seluanov, Andrei; Chen, Zhuoxun; Hine, Christopher; Sasahara, Tais H. C.; Ribeiro, Antonio A. C. M.; Catania, Kenneth C.; Presgraves, Daven C.; Gorbunova, Vera

    2009-01-01

    Summary In multicellular organisms, telomerase is required to maintain telomere length in the germline but is dispensable in the soma. Mice, for example, express telomerase in somatic and germline tissues, while humans express telomerase almost exclusively in the germline. As a result, when telomeres of human somatic cells reach a critical length the cells enter irreversible growth arrest called replicative senescence. Replicative senescence is believed to be an anticancer mechanism that limits cell proliferation. The difference between mice and humans led to the hypothesis that repression of telomerase in somatic cells has evolved as a tumor-suppressor adaptation in large, long-lived organisms. We tested whether regulation of telomerase activity coevolves with lifespan and body mass using comparative analysis of 15 rodent species with highly diverse lifespans and body masses. Here we show that telomerase activity does not coevolve with lifespan but instead coevolves with body mass: larger rodents repress telomerase activity in somatic cells. These results suggest that large body mass presents a greater risk of cancer than long lifespan, and large animals evolve repression of telomerase activity to mitigate that risk. PMID:17173545

  15. Acyl chain length of phosphatidylserine is correlated with plant lifespan.

    Directory of Open Access Journals (Sweden)

    Yan Li

    Full Text Available Plant lifespan is affected by factors with genetic and environmental bases. The laws governing these two factors and how they affect plant lifespan are unclear. Here we show that the acyl chain length (ACL of phosphatidylserine (PS is correlated with plant lifespan. Among the detected eight head-group classes of membrane lipids with lipidomics based on triple quadrupole tandem mass spectrometry, the ACL of PS showed high diversity, in contrast to the ACLs of the other seven classes, which were highly conserved over all stages of development in all plant species and organs and under all conditions that we studied. Further investigation found that acyl chains of PS lengthened during development, senescence, and under environmental stresses and that increasing length was accelerated by promoted- senescence. The acyl chains of PS were limited to a certain carbon number and ceased to increase in length when plants were close to death. These findings suggest that the ACL of PS can count plant lifespan and could be a molecular scale ruler for measuring plant development and senescence.

  16. Materialism across the lifespan : An age-period-cohort analysis

    NARCIS (Netherlands)

    Jaspers, Esther; Pieters, Rik

    This research examined the development of materialism across the lifespan. Two initial studies revealed that: 1) lay beliefs were that materialism declines with age; and 2) previous research findings also implied a modest, negative relationship between age and materialism. Yet, previous research has

  17. Plant adaptogens increase lifespan and stress resistance in C. elegans

    NARCIS (Netherlands)

    Wiegant, F.A.C.; Surinova, S.; Ytsma, E.; Langelaar-Makkinje, M.; Wikman, G.; Post, J.A.

    2008-01-01

    Extracts of plant adaptogens such as Eleutherococcus senticosus (or Acanthopanax senticosus) and Rhodiola rosea can increase stress resistance in several model systems. We now show that both extracts also increase the mean lifespan of the nematode C. elegans in a dose-dependent way. In

  18. Engineering Substantially Prolonged Human Lifespans: Biotechnological Enhancement and Ethics

    NARCIS (Netherlands)

    Derkx, P.H.J.M.

    2006-01-01

    Substantial extension of the human lifespan has recently become a subject of lively debate. One reason for this is the completion in 2001 of the Human Genome Project and the experimental avenues for biogerontological research it has opened. Another is recent theoretical progress in biogerontology.

  19. Epigenetic Contributions to Cognitive Aging: Disentangling Mindspan and Lifespan

    Science.gov (United States)

    Spiegel, Amy M.; Sewal, Angila S.; Rapp, Peter R.

    2014-01-01

    Epigenetic modifications of chromatin structure provide a mechanistic interface for gene-environment interactions that impact the individualization of health trajectories across the lifespan. A growing body of research indicates that dysfunctional epigenetic regulation contributes to poor cognitive outcomes among aged populations. Here we review…

  20. Sphingolipid metabolism regulates development and lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Cutler, Roy G; Thompson, Kenneth W; Camandola, Simonetta; Mack, Kendra T; Mattson, Mark P

    2014-12-15

    Sphingolipids are a highly conserved lipid component of cell membranes involved in the formation of lipid raft domains that house many of the receptors and cell-to-cell signaling factors involved in regulating cell division, maturation, and terminal differentiation. By measuring and manipulating sphingolipid metabolism using pharmacological and genetic tools in Caenorhabditis elegans, we provide evidence that the synthesis and remodeling of specific ceramides (e.g., dC18:1-C24:1), gangliosides (e.g., GM1-C24:1), and sphingomyelins (e.g., dC18:1-C18:1) influence development rate and lifespan. We found that the levels of fatty acid chain desaturation and elongation in many sphingolipid species increased during development and aging, with no such changes in developmentally-arrested dauer larvae or normal adults after food withdrawal (an anti-aging intervention). Pharmacological inhibitors and small interfering RNAs directed against serine palmitoyl transferase and glucosylceramide synthase acted to slow development rate, extend the reproductive period, and increase lifespan. In contrast, worms fed an egg yolk diet rich in sphingolipids exhibited accelerated development and reduced lifespan. Our findings demonstrate that sphingolipid accumulation and remodeling are critical events that determine development rate and lifespan in the nematode model, with both development rate and aging being accelerated by the synthesis of sphingomyelin, and its metabolism to ceramides and gangliosides.

  1. Portraits of life: Patterns of events over the lifespan

    NARCIS (Netherlands)

    Schroots, J.J.F.; Assink, M.H.J.

    2005-01-01

    This explorative content-analytic study completes earlier studies on the lifespan distributions of number and affect of past and future life-events, collected by means of the Life-line Interview Method (LIM), for three age groups of men and women (young, middle and late adulthood). LIM events were c

  2. Acyl chain length of phosphatidylserine is correlated with plant lifespan.

    Science.gov (United States)

    Li, Yan; Zheng, Guowei; Jia, Yanxia; Yu, Xiaomei; Zhang, Xudong; Yu, Buzhu; Wang, Dandan; Zheng, Yanling; Tian, Xuejun; Li, Weiqi

    2014-01-01

    Plant lifespan is affected by factors with genetic and environmental bases. The laws governing these two factors and how they affect plant lifespan are unclear. Here we show that the acyl chain length (ACL) of phosphatidylserine (PS) is correlated with plant lifespan. Among the detected eight head-group classes of membrane lipids with lipidomics based on triple quadrupole tandem mass spectrometry, the ACL of PS showed high diversity, in contrast to the ACLs of the other seven classes, which were highly conserved over all stages of development in all plant species and organs and under all conditions that we studied. Further investigation found that acyl chains of PS lengthened during development, senescence, and under environmental stresses and that increasing length was accelerated by promoted- senescence. The acyl chains of PS were limited to a certain carbon number and ceased to increase in length when plants were close to death. These findings suggest that the ACL of PS can count plant lifespan and could be a molecular scale ruler for measuring plant development and senescence.

  3. The lifespan of lexical traces for novel morphologically complex words

    NARCIS (Netherlands)

    Vaan, L. de; Ernestus, M.T.C.; Schreuder, R.

    2011-01-01

    This study investigates the lifespans of lexical traces for novel morphologically complex words. In two visual lexical decision experiments, a neologism was either primed by itself or by its stem. The target occurred 40 trials after the prime (Experiments 1 & 2), after a 12 hour delay (Experiment 1)

  4. Lifespan extension and increased resistance to environmental stressors by N-Acetyl-L-Cysteine in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Seung-Il Oh

    2015-05-01

    Full Text Available OBJECTIVE: This study was performed to determine the effect of N-acetyl-L-cysteine, a modified sulfur-containing amino acid that acts as a strong cellular antioxidant, on the response to environmental stressors and on aging in C. elegans. METHOD: The survival of worms under oxidative stress conditions induced by paraquat was evaluated with and without in vivo N-acetyl-L-cysteine treatment. The effect of N-acetyl-L-cysteine on the response to other environmental stressors, including heat stress and ultraviolet irradiation (UV, was also monitored. To investigate the effect on aging, we examined changes in lifespan, fertility, and expression of age-related biomarkers in C. elegans after N-acetyl-L-cysteine treatment. RESULTS: Dietary N-acetyl-L-cysteine supplementation significantly increased resistance to oxidative stress, heat stress, and UV irradiation in C. elegans. In addition, N-acetyl-L-cysteine supplementation significantly extended both the mean and maximum lifespan of C. elegans. The mean lifespan was extended by up to 30.5% with 5 mM N-acetyl-L-cysteine treatment, and the maximum lifespan was increased by 8 days. N-acetyl-L-cysteine supplementation also increased the total number of progeny produced and extended the gravid period of C. elegans. The green fluorescent protein reporter assay revealed that expression of the stress-responsive genes, sod-3 and hsp-16.2, increased significantly following N-acetyl-L-cysteine treatment. CONCLUSION: N-acetyl-L-cysteine supplementation confers a longevity phenotype in C. elegans, possibly through increased resistance to environmental stressors.

  5. Caloric restriction extends yeast chronological lifespan by altering a pattern of age-related changes in trehalose concentration

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    Pavlo eKyryakov

    2012-07-01

    Full Text Available The nonreducing disaccharide trehalose has been long considered only as a reserve carbohydrate. However, recent studies in yeast suggested that this osmolyte can protect cells and cellular proteins from oxidative damage elicited by exogenously added reactive oxygen species (ROS. Trehalose has been also shown to affect stability, folding and aggregation of bacterial and firefly proteins heterologously expressed in heat-shocked yeast cells. Our recent investigation of how a lifespan-extending caloric restriction (CR diet alters the metabolic history of chronologically aging yeast suggested that their longevity is programmed by the level of metabolic capacity - including trehalose biosynthesis and degradation - that yeast cells developed prior to entry into quiescence. To investigate whether trehalose homeostasis in chronologically aging yeast may play a role in longevity extension by CR, in this study we examined how single-gene-deletion mutations affecting trehalose biosynthesis and degradation impact 1 the age-related dynamics of changes in trehalose concentration; 2 yeast chronological lifespan under CR conditions; 3 the chronology of oxidative protein damage, intracellular ROS level and protein aggregation; and 4 the timeline of thermal inactivation of a protein in heat-shocked yeast cells and its subsequent reactivation in yeast returned to low temperature. Our data imply that CR extends yeast chronological lifespan in part by altering a pattern of age-related changes in trehalose concentration. We outline a model for molecular mechanisms underlying the essential role of trehalose in defining yeast longevity by modulating protein folding, misfolding, unfolding, refolding, oxidative damage, solubility and aggregation throughout lifespan.

  6. Mitochondrial stress extends lifespan in C. elegans through neuronal hormesis.

    Science.gov (United States)

    Maglioni, Silvia; Schiavi, Alfonso; Runci, Alessandra; Shaik, Anjumara; Ventura, Natascia

    2014-08-01

    Progressive neuronal deterioration accompanied by sensory functions decline is typically observed during aging. On the other hand, structural or functional alterations of specific sensory neurons extend lifespan in the nematode Caenorhabditis elegans. Hormesis is a phenomenon by which the body benefits from moderate stress of various kinds which at high doses are harmful. Several studies indicate that different stressors can hormetically extend lifespan in C. elegans and suggest that hormetic effects could be exploited as a strategy to slow down aging and the development of age-associated (neuronal) diseases in humans. Mitochondria play a central role in the aging process and hormetic-like bimodal dose-response effects on C. elegans lifespan have been observed following different levels of mitochondrial stress. Here we tested the hypothesis that mitochondrial stress may hormetically extend C. elegans lifespan through subtle neuronal alterations. In support of our hypothesis we find that life-lengthening dose of mitochondrial stress reduces the functionality of a subset of ciliated sensory neurons in young animals. Notably, the same pro-longevity mitochondrial treatments rescue the sensory deficits in old animals. We also show that mitochondrial stress extends C. elegans lifespan acting in part through genes required for the functionality of those neurons. To our knowledge this is the first study describing a direct causal connection between sensory neuron dysfunction and extended longevity following mitochondrial stress. Our work supports the potential anti-aging effect of neuronal hormesis and open interesting possibility for the development of therapeutic strategy for age-associated neurodegenerative disorders.

  7. Supplementation of Spirulina (Arthrospira platensis) Improves Lifespan and Locomotor Activity in Paraquat-Sensitive DJ-1β(Δ93) Flies, a Parkinson's Disease Model in Drosophila melanogaster.

    Science.gov (United States)

    Kumar, Ajay; Christian, Pearl K; Panchal, Komal; Guruprasad, B R; Tiwari, Anand K

    2017-09-03

    Spirulina (Arthrospira platensis) is a cyanobacterium (blue-green alga) consumed by humans and other animals because of its nutritional values and pharmacological properties. Apart from high protein contents, it also contains high levels of antioxidant and anti-inflammatory compounds, such as carotenoids, β-carotene, phycocyanin, and phycocyanobilin, indicating its possible pharmaco-therapeutic utility. In the present study using DJ-1β(Δ93) flies, a Parkinson's disease model in Drosophila, we have demonstrated the therapeutic effect of spirulina and its active component C-phycocyanin (C-PC) in the improvement of lifespan and locomotor behavior. Our findings indicate that dietary supplementation of spirulina significantly improves the lifespan and locomotor activity of paraquat-fed DJ-1β(Δ93) flies. Furthermore, supplementation of spirulina and C-PC individually and independently reduced the cellular stress marked by deregulating the expression of heat shock protein 70 and Jun-N-terminal kinase signaling in DJ-1β(Δ93) flies. A significant decrease in superoxide dismutase and catalase activities in spirulina-fed DJ-1β(Δ93) flies tends to indicate the involvement of antioxidant properties associated with spirulina in the modulation of stress-induced signaling and improvement in lifespan and locomotor activity in Drosophila DJ-1β(Δ93) flies. Our results suggest that antioxidant boosting properties of spirulina can be used as a nutritional supplement for improving the lifespan and locomotor behavior in Parkinson's disease.

  8. Myc-dependent genome instability and lifespan in Drosophila.

    Directory of Open Access Journals (Sweden)

    Christina Greer

    Full Text Available The Myc family of transcription factors are key regulators of cell growth and proliferation that are dysregulated in a large number of human cancers. When overexpressed, Myc family proteins also cause genomic instability, a hallmark of both transformed and aging cells. Using an in vivo lacZ mutation reporter, we show that overexpression of Myc in Drosophila increases the frequency of large genome rearrangements associated with erroneous repair of DNA double-strand breaks (DSBs. In addition, we find that overexpression of Myc shortens adult lifespan and, conversely, that Myc haploinsufficiency reduces mutation load and extends lifespan. Our data provide the first evidence that Myc may act as a pro-aging factor, possibly through its ability to greatly increase genome instability.

  9. Lifespan trends of autobiographical remembering: episodicity and search for meaning.

    Science.gov (United States)

    Habermas, Tilmann; Diel, Verena; Welzer, Harald

    2013-09-01

    Autobiographical memories of older adults show fewer episodic and more non-episodic elements than those of younger adults. This semantization effect is attributed to a loss of episodic memory ability. However the alternative explanation by an increasing proclivity to search for meaning has not been ruled out to date. To test whether a decrease in episodicity and an increase in meaning-making in autobiographical narratives are related across the lifespan, we used different instructions, one focussing on specific episodes, the other on embedding events in life, in two lifespan samples. A continuous decrease of episodic quality of memory (memory specificity, narrative quality) was confirmed. An increase of search for meaning (interpretation, life story integration) was confirmed only up to middle adulthood. This non-inverse development of episodicity and searching for meaning in older age speaks for an autonomous semantization effect that is not merely due to an increase in interpretative preferences.

  10. The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin.

    Directory of Open Access Journals (Sweden)

    Dayle McClintock

    Full Text Available Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670 is a rare disorder characterized by accelerated aging and early death, frequently from stroke or coronary artery disease. 90% of HGPS cases carry the LMNA G608G (GGC>GGT mutation within exon 11 of LMNA, activating a splice donor site that results in production of a dominant negative form of lamin A protein, denoted progerin. Screening 150 skin biopsies from unaffected individuals (newborn to 97 years showed that a similar splicing event occurs in vivo at a low level in the skin at all ages. While progerin mRNA remains low, the protein accumulates in the skin with age in a subset of dermal fibroblasts and in a few terminally differentiated keratinocytes. Progerin-positive fibroblasts localize near the basement membrane and in the papillary dermis of young adult skin; however, their numbers increase and their distribution reaches the deep reticular dermis in elderly skin. Our findings demonstrate that progerin expression is a biomarker of normal cellular aging and may potentially be linked to terminal differentiation and senescence in elderly individuals.

  11. The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin.

    Science.gov (United States)

    McClintock, Dayle; Ratner, Desiree; Lokuge, Meepa; Owens, David M; Gordon, Leslie B; Collins, Francis S; Djabali, Karima

    2007-12-05

    Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare disorder characterized by accelerated aging and early death, frequently from stroke or coronary artery disease. 90% of HGPS cases carry the LMNA G608G (GGC>GGT) mutation within exon 11 of LMNA, activating a splice donor site that results in production of a dominant negative form of lamin A protein, denoted progerin. Screening 150 skin biopsies from unaffected individuals (newborn to 97 years) showed that a similar splicing event occurs in vivo at a low level in the skin at all ages. While progerin mRNA remains low, the protein accumulates in the skin with age in a subset of dermal fibroblasts and in a few terminally differentiated keratinocytes. Progerin-positive fibroblasts localize near the basement membrane and in the papillary dermis of young adult skin; however, their numbers increase and their distribution reaches the deep reticular dermis in elderly skin. Our findings demonstrate that progerin expression is a biomarker of normal cellular aging and may potentially be linked to terminal differentiation and senescence in elderly individuals.

  12. Cardioprotection and lifespan extension by the natural polyamine spermidine

    OpenAIRE

    Eisenberg, Tobias; Abdellatif, Mahmoud; Schroeder, Sabrina; Primessnig, Uwe; Stekovic, Slaven; Pendl, Tobias; Harger, Alexandra; Schipke, Julia; Zimmermann, Andreas; SCHMIDT, Albrecht; Tong, Mingming; Ruckenstuhl, Christoph; Dammbrueck, Christopher; Gross, Angelina S; Herbst, Viktoria

    2016-01-01

    Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin...

  13. Pomegranate juice enhances healthy lifespan in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Padmavathy eVenkatasubramanian

    2014-12-01

    Full Text Available Exploring innovative ways to ensure healthy ageing of populations is a pre-requisite to contain rising healthcare costs. Scientific research into the principles and practices of traditional medicines can provide new insights and simple solutions to lead a healthy life. Rasayana is a dedicated branch of Ayurveda (an Indian medicine that deals with methods to increase vitality and delay aging through the use of diet, herbal supplements and other lifestyle practices. The life-span and health-span enhancing actions of the fruits of Pomegranate (Punica granatum L., a well-known Rasayana, were tested on Drosophila melanogaster (fruitfly model. Supplementation of standard corn meal with 10% (v/v pomegranate juice (PJ extended the life-span of male and female flies by 18% and 8% respectively. When male and female flies were mixed and reared together, there was 19% increase in the longevity of PJ fed flies, as assessed by MSD, the median survival day (24.8. MSD for control and resveratrol (RV groups was at 20.8 and 23.1 days respectively. A two-fold enhancement in fecundity, improved resistance to oxidative stress (H2O2 and paraquat induced and to Candida albicans infection were observed in PJ fed flies. Further, the flies in the PJ fed group were physically active over an extended period of time, as assessed by the climbing assay. PJ thus outperformed both control and RV groups in the life-span and health-span parameters tested. This study provides the scope to explore the potential of PJ as a nutraceutical to improve health span and lifespan in humans.

  14. Copy number variations in alternative splicing gene networks impact lifespan.

    Directory of Open Access Journals (Sweden)

    Joseph T Glessner

    Full Text Available Longevity has a strong genetic component evidenced by family-based studies. Lipoprotein metabolism, FOXO proteins, and insulin/IGF-1 signaling pathways in model systems have shown polygenic variations predisposing to shorter lifespan. To test the hypothesis that rare variants could influence lifespan, we compared the rates of CNVs in healthy children (0-18 years of age with individuals 67 years or older. CNVs at a significantly higher frequency in the pediatric cohort were considered risk variants impacting lifespan, while those enriched in the geriatric cohort were considered longevity protective variants. We performed a whole-genome CNV analysis on 7,313 children and 2,701 adults of European ancestry genotyped with 302,108 SNP probes. Positive findings were evaluated in an independent cohort of 2,079 pediatric and 4,692 geriatric subjects. We detected 8 deletions and 10 duplications that were enriched in the pediatric group (P=3.33×10(-8-1.6×10(-2 unadjusted, while only one duplication was enriched in the geriatric cohort (P=6.3×10(-4. Population stratification correction resulted in 5 deletions and 3 duplications remaining significant (P=5.16×10(-5-4.26×10(-2 in the replication cohort. Three deletions and four duplications were significant combined (combined P=3.7×10(-4-3.9×10(-2. All associated loci were experimentally validated using qPCR. Evaluation of these genes for pathway enrichment demonstrated ~50% are involved in alternative splicing (P=0.0077 Benjamini and Hochberg corrected. We conclude that genetic variations disrupting RNA splicing could have long-term biological effects impacting lifespan.

  15. Food Insecurity and Health across the Lifespan12

    OpenAIRE

    Lee, Jung Sun; Gundersen, Craig; Cook, John; Laraia, Barbara; Johnson, Mary Ann

    2012-01-01

    Our symposium entitled, “Food Insecurity and Health across the Lifespan” explored the latest research from the economic, medical, pediatric, geriatric, and nutrition literature concerning the measurement, prevalence, predictors, and consequences of food insecurity across the lifespan, with a focus on chronic disease, chronic disease management, and healthcare costs. Consideration of the health impacts of food insecurity is a new and timely area of research, with a considerable potential for t...

  16. Lifespan behavioural and neural resilience in a social insect.

    Science.gov (United States)

    Giraldo, Ysabel Milton; Kamhi, J Frances; Fourcassié, Vincent; Moreau, Mathieu; Robson, Simon K A; Rusakov, Adina; Wimberly, Lindsey; Diloreto, Alexandria; Kordek, Adrianna; Traniello, James F A

    2016-01-13

    Analyses of senescence in social species are important to understanding how group living influences the evolution of ageing in society members. Social insects exhibit remarkable lifespan polyphenisms and division of labour, presenting excellent opportunities to test hypotheses concerning ageing and behaviour. Senescence patterns in other taxa suggest that behavioural performance in ageing workers would decrease in association with declining brain functions. Using the ant Pheidole dentata as a model, we found that 120-day-old minor workers, having completed 86% of their laboratory lifespan, showed no decrease in sensorimotor functions underscoring complex tasks such as alloparenting and foraging. Collaterally, we found no age-associated increases in apoptosis in functionally specialized brain compartments or decreases in synaptic densities in the mushroom bodies, regions associated with integrative processing. Furthermore, brain titres of serotonin and dopamine--neuromodulators that could negatively impact behaviour through age-related declines--increased in old workers. Unimpaired task performance appears to be based on the maintenance of brain functions supporting olfaction and motor coordination independent of age. Our study is the first to comprehensively assess lifespan task performance and its neurobiological correlates and identify constancy in behavioural performance and the absence of significant age-related neural declines.

  17. Supply Chain Batching Problem with Identical Orders and Lifespan

    Directory of Open Access Journals (Sweden)

    Shanlin Li

    2015-01-01

    Full Text Available In the real world, there are a large number of supply chains that involve the short lifespan products. In this paper, we consider an integrated production and distribution batch scheduling problem on a single machine for the orders with a short lifespan, because it may be cheaper or faster to process and distribute orders in a batch than to process and distribute them individually. Assume that the orders have the identical processing time and come from the same location, and the batch setup time is a constant. The problem is to choose the number of batches and batch sizes to minimize the total delivery time without violating the order lifespan. We first give a backward dynamic programming algorithm, but it is not an actually polynomial-time algorithm. Then we propose a constant time partial dynamic programming algorithm by doing further research into the recursion formula in the algorithm. Further, using the difference characteristics of the optimal value function, a specific calculating formula to solve the problem with the setup time being integer times of the processing time is obtained.

  18. Ontogeny of morningness-eveningness across the adult human lifespan

    Science.gov (United States)

    Randler, Christoph

    2016-02-01

    Sleep timing of humans can be classified alongside a continuum from early to late sleepers, with some people (larks) having an early activity, early bed, and rise times and others (owls) with a more nocturnally orientated activity. Only a few studies reported that morningness-eveningness changes significantly during the adult lifespan based on community samples. Here, I applied a different methodological approach to seek for evidence for the age-related changes in morningness-eveningness preferences by using a meta-data from all available studies. The new aspect of this cross-sectional approach is that only a few studies themselves address the age-related changes of the adult lifespan development, but that many studies are available that provide exactly the data needed. The studies came from 27 countries and included 36,939 participants. Age was highly significantly correlated with scores on the Composite Scale of Morningness ( r = 0.70). This relationship seems linear, because a linear regression explained nearly the same amount of variance compared to other models such as logarithmic, quadratic, or cubic models. The standard deviation of age correlated with the standard deviation of CSM scores ( r = 0.55), suggesting when there is much variance in age in a study; in turn, there is much variance in morningness. This meta-analytical approach shows that morningness-eveningness changes across the adult lifespan and that older age is related to higher morningness.

  19. Red blood cell lifespan, erythropoiesis and hemoglobin control.

    Science.gov (United States)

    Kruse, Anja; Uehlinger, Dominik E; Gotch, Frank; Kotanko, Peter; Levin, Nathan W

    2008-01-01

    Erythropoietin (EPO) and iron deficiency as causes of anemia in patients with limited renal function or end-stage renal disease are well addressed. The concomitant impairment of red blood cell (RBC) survival has been largely neglected. Properties of the uremic environment like inflammation, increased oxidative stress and uremic toxins seem to be responsible for the premature changes in RBC membrane and cytoskeleton. The exposure of antigenic sites and breakdown of the phosphatidylserine asymmetry promote RBC phagocytosis. While the individual response to treatment with EPO-stimulating agents (ESA) depends on both the RBC's lifespan and the production rate, uniform dosing algorithms do not meet that demand. The clinical use of mathematical models predicting ESA-induced changes in hematocrit might be greatly improved once independent estimates of RBC production rate and/or lifespan become available, thus making the concomitant estimation of both parameters unnecessary. Since heme breakdown by the hemoxygenase pathway results in carbon monoxide (CO) which is exhaled, a simple CO breath test has been used to calculate hemoglobin turnover and therefore RBC survival and lifespan. Future research will have to be done to validate and implement this method in patients with kidney failure. This will result in new insights into RBC kinetics in renal patients. Eventually, these findings are expected to improve our understanding of the hemoglobin variability in response to ESA.

  20. DNA repair in species with extreme lifespan differences

    Science.gov (United States)

    MacRae, Sheila L.; Croken, Matthew McKnight; Calder, R.B.; Aliper, Alexander; Milholland, Brandon; White, Ryan R.; Zhavoronkov, Alexander; Gladyshev, Vadim N.; Seluanov, Andrei; Gorbunova, Vera; Zhang, Zhengdong D.; Vijg, Jan

    2015-01-01

    Differences in DNA repair capacity have been hypothesized to underlie the great range of maximum lifespans among mammals. However, measurements of individual DNA repair activities in cells and animals have not substantiated such a relationship because utilization of repair pathways among animals—depending on habitats, anatomical characteristics, and life styles—varies greatly between mammalian species. Recent advances in high-throughput genomics, in combination with increased knowledge of the genetic pathways involved in genome maintenance, now enable a comprehensive comparison of DNA repair transcriptomes in animal species with extreme lifespan differences. Here we compare transcriptomes of liver, an organ with high oxidative metabolism and abundant spontaneous DNA damage, from humans, naked mole rats, and mice, with maximum lifespans of ∼120, 30, and 3 years, respectively, with a focus on genes involved in DNA repair. The results show that the longer-lived species, human and naked mole rat, share higher expression of DNA repair genes, including core genes in several DNA repair pathways. A more systematic approach of signaling pathway analysis indicates statistically significant upregulation of several DNA repair signaling pathways in human and naked mole rat compared with mouse. The results of this present work indicate, for the first time, that DNA repair is upregulated in a major metabolic organ in long-lived humans and naked mole rats compared with short-lived mice. These results strongly suggest that DNA repair can be considered a genuine longevity assurance system. PMID:26729707

  1. Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans

    Science.gov (United States)

    Shen, En-Zhi; Song, Chun-Qing; Lin, Yuan; Zhang, Wen-Hong; Su, Pei-Fang; Liu, Wen-Yuan; Zhang, Pan; Xu, Jiejia; Lin, Na; Zhan, Cheng; Wang, Xianhua; Shyr, Yu; Cheng, Heping; Dong, Meng-Qiu

    2014-04-01

    It has been theorized for decades that mitochondria act as the biological clock of ageing, but the evidence is incomplete. Here we show a strong coupling between mitochondrial function and ageing by in vivo visualization of the mitochondrial flash (mitoflash), a frequency-coded optical readout reflecting free-radical production and energy metabolism at the single-mitochondrion level. Mitoflash activity in Caenorhabditis elegans pharyngeal muscles peaked on adult day 3 during active reproduction and on day 9 when animals started to die off. A plethora of genetic mutations and environmental factors inversely modified the lifespan and the day-3 mitoflash frequency. Even within an isogenic population, the day-3 mitoflash frequency was negatively correlated with the lifespan of individual animals. Furthermore, enhanced activity of the glyoxylate cycle contributed to the decreased day-3 mitoflash frequency and the longevity of daf-2 mutant animals. These results demonstrate that the day-3 mitoflash frequency is a powerful predictor of C. elegans lifespan across genetic, environmental and stochastic factors. They also support the notion that the rate of ageing, although adjustable in later life, has been set to a considerable degree before reproduction ceases.

  2. Rapamycin extends murine lifespan but has limited effects on aging.

    Science.gov (United States)

    Neff, Frauke; Flores-Dominguez, Diana; Ryan, Devon P; Horsch, Marion; Schröder, Susanne; Adler, Thure; Afonso, Luciana Caminha; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Garrett, Lillian; Hans, Wolfgang; Hettich, Moritz M; Holtmeier, Richard; Hölter, Sabine M; Moreth, Kristin; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Rozman, Jan; Naton, Beatrix; Ordemann, Rainer; Adamski, Jerzy; Beckers, Johannes; Bekeredjian, Raffi; Busch, Dirk H; Ehninger, Gerhard; Graw, Jochen; Höfler, Heinz; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Stypmann, Jörg; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabe de Angelis, Martin; Ehninger, Dan

    2013-08-01

    Aging is a major risk factor for a large number of disorders and functional impairments. Therapeutic targeting of the aging process may therefore represent an innovative strategy in the quest for novel and broadly effective treatments against age-related diseases. The recent report of lifespan extension in mice treated with the FDA-approved mTOR inhibitor rapamycin represented the first demonstration of pharmacological extension of maximal lifespan in mammals. Longevity effects of rapamycin may, however, be due to rapamycin's effects on specific life-limiting pathologies, such as cancers, and it remains unclear if this compound actually slows the rate of aging in mammals. Here, we present results from a comprehensive, large-scale assessment of a wide range of structural and functional aging phenotypes, which we performed to determine whether rapamycin slows the rate of aging in male C57BL/6J mice. While rapamycin did extend lifespan, it ameliorated few studied aging phenotypes. A subset of aging traits appeared to be rescued by rapamycin. Rapamycin, however, had similar effects on many of these traits in young animals, indicating that these effects were not due to a modulation of aging, but rather related to aging-independent drug effects. Therefore, our data largely dissociate rapamycin's longevity effects from effects on aging itself.

  3. Plant adaptogens increase lifespan and stress resistance in C. elegans.

    Science.gov (United States)

    Wiegant, F A C; Surinova, S; Ytsma, E; Langelaar-Makkinje, M; Wikman, G; Post, J A

    2009-02-01

    Extracts of plant adaptogens such as Eleutherococcus senticosus (or Acanthopanax senticosus) and Rhodiola rosea can increase stress resistance in several model systems. We now show that both extracts also increase the mean lifespan of the nematode C. elegans in a dose-dependent way. In at least four independent experiments, 250 microg/ml Eleutherococcus (SHE-3) and 10-25 microg/ml Rhodiola (SHR-5) significantly increased life span between 10 and 20% (P adaptogen extracts were also able to increase stress resistance in C. elegans: against a relatively short heat shock (35 degrees C during 3 h) as well as chronic heat treatment at 26 degrees C. An increase against chronic oxidative stress conditions was observed in mev-1 mutants, and during exposure of the wild type nematode to paraquat (10 mM) or UV stress, be it less efficiently. Concerning the mode of action: both adaptogens induce translocation of the DAF-16 transcription factor from the cytoplasm into the nucleus, suggesting a reprogramming of transcriptional activities favoring the synthesis of proteins involved in stress resistance (such as the chaperone HSP-16) and longevity. Based on these observations, it is suggested that adaptogens are experienced as mild stressors at the lifespan-enhancing concentrations and thereby induce increased stress resistance and a longer lifespan.

  4. Resveratrol extends lifespan and preserves glia but not neurons of the Nothobranchius guentheri optic tectum.

    Science.gov (United States)

    Genade, T; Lang, D M

    2013-02-01

    Resveratrol is reported as having neuroprotective properties, however, much of this reputation has come from research using disease and injury models of neurodegeneration and not neurodegenerative-ageing. The results published here pertain to the affect resveratrol has on neurodegenerative-ageing. Resveratrol had previously been used to extend the lifespan of Nothobranchius furzeri wherein it preserved cognition and reduced ageing-associated neurodegeneration. No cell-type specific antibodies were then identified which could be used to investigate the nature of the neurodegeneration or resveratrols effect on CNS cells. Using wholemounts stained with SMI31 anti-phospho-neurolament, GA-5 and DAKO Z0334 anti-GFAP antibodies, E587 antiserum against NCAMs and anti-tenascin-R antibodies we determined what cellular changes occurred with age in the optic tectum of Nothobranchius guentheri. We show that resveratrol-treatment extended the lifespan of N. guentheri but did not preserve neuron density of the optic tectum stratum griseum superciale even though it did reduce the proportion of degenerate (SMI31 antigen accumulating) neurons in the optic tectum. Resveratrol-treatment did prevent the ageing-dependent loss of radial glia lining the optic tectum of N. guentheri. The ageing-related loss of NCAM expression and tenascin-R expressing perineuronal nets was also prevented by resveratrol-treatment. Glial and perineuronal density as well as NCAM expression appear to correlate well with age. These results suggest that the anti-ageing properties of resveratrol in vertebrates may be unrelated to the protection of neurons.

  5. Worker lifespan is an adaptive trait during colony establishment in the long-lived ant Lasius niger

    NARCIS (Netherlands)

    Kramer, Boris H.; Schaible, Ralf; Scheuerlein, Alexander

    2016-01-01

    Eusociality has been recognized as a strong driver of lifespan evolution. While queens show extraordinary lifespans of 20 years and more, worker lifespan is short and variable. A recent comparative study found that in eusocial species with larger average colony sizes the disparities in the lifespans

  6. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins.

    Science.gov (United States)

    Michishita, Eriko; Park, Jean Y; Burneskis, Jenna M; Barrett, J Carl; Horikawa, Izumi

    2005-10-01

    Sir2 is a NAD+-dependent protein deacetylase that extends lifespan in yeast and worms. This study examines seven human proteins homologous to Sir2 (SIRT1 through SIRT7) for cellular localization, expression profiles, protein deacetylation activity, and effects on human cell lifespan. We found that: 1) three nuclear SIRT proteins (SIRT1, SIRT6, and SIRT7) show different subnuclear localizations: SIRT6 and SIRT7 are associated with heterochromatic regions and nucleoli, respectively, where yeast Sir2 functions; 2) SIRT3, SIRT4, and SIRT5 are localized in mitochondria, an organelle that links aging and energy metabolism; 3) cellular p53 is a major in vivo substrate of SIRT1 deacetylase, but not the other six SIRT proteins; 4) SIRT1, but not the other two nuclear SIRT proteins, shows an in vitro deacetylase activity on histone H4 and p53 peptides; and 5) overexpression of any one of the seven SIRT proteins does not extend cellular replicative lifespan in normal human fibroblasts or prostate epithelial cells. This study supports the notion that multiple human SIRT proteins have evolutionarily conserved and nonconserved functions at different cellular locations and reveals that the lifespan of normal human cells, in contrast to that of lower eukaryotes, cannot be manipulated by increased expression of a single SIRT protein.

  7. Complementary roles of mitochondrial respiration and ROS signaling on cellular aging and longevity.

    Science.gov (United States)

    Barrientos, Antoni

    2012-09-01

    Although it is widely accepted that mitochondria play fundamental roles in the mechanisms of cellular and organismal aging and lifespan extension, some open questions remain concerning the requirements for aerobic energy production and the effect of the potentially hazardous reactive oxygen species (ROS) byproducts as well as their interplay with nutrition and caloric intake.

  8. Long lifespans have evolved with long and monounsaturated fatty acids in birds.

    Science.gov (United States)

    Galván, Ismael; Naudí, Alba; Erritzøe, Johannes; Møller, Anders P; Barja, Gustavo; Pamplona, Reinald

    2015-10-01

    The evolution of lifespan is a central question in evolutionary biology, begging the question why there is so large variation among taxa. Specifically, a central quest is to unravel proximate causes of ageing. Here, we show that the degree of unsaturation of liver fatty acids predicts maximum lifespan in 107 bird species. In these birds, the degree of fatty acid unsaturation is positively related to maximum lifespan across species. This is due to a positive effect of monounsaturated fatty acid content, while polyunsaturated fatty acid content negatively correlates with maximum lifespan. Furthermore, fatty acid chain length unsuspectedly increases with maximum lifespan independently of degree of unsaturation. These findings tune theories on the proximate causes of ageing while providing evidence that the evolution of lifespan in birds occurs in association with fatty acid profiles. This suggests that studies of proximate and ultimate questions may facilitate our understanding of these central evolutionary questions.

  9. The anticonvulsant ethosuximide disrupts sensory function to extend C. elegans lifespan.

    Directory of Open Access Journals (Sweden)

    James J Collins

    2008-10-01

    Full Text Available Ethosuximide is a medication used to treat seizure disorders in humans, and we previously demonstrated that ethosuximide can delay age-related changes and extend the lifespan of the nematode Caenorhabditis elegans. The mechanism of action of ethosuximide in lifespan extension is unknown, and elucidating how ethosuximide functions is important for defining endogenous processes that influence lifespan and for exploring the potential of ethosuximide as a therapeutic for age-related diseases. To identify genes that mediate the activity of ethosuximide, we conducted a genetic screen and identified mutations in two genes, che-3 and osm-3, that cause resistance to ethosuximide-mediated toxicity. Mutations in che-3 and osm-3 cause defects in overlapping sets of chemosensory neurons, resulting in defective chemosensation and an extended lifespan. These findings suggest that ethosuximide extends lifespan by inhibiting the function of specific chemosensory neurons. This model is supported by the observation that ethosuximide-treated animals displayed numerous phenotypic similarities with mutants that have chemosensory defects, indicating that ethosuximide inhibits chemosensory function. Furthermore, ethosuximide extends lifespan by inhibiting chemosensation, since the long-lived osm-3 mutants were resistant to the lifespan extension caused by ethosuximide. These studies demonstrate a novel mechanism of action for a lifespan-extending drug and indicate that sensory perception has a critical role in controlling lifespan. Sensory perception also influences the lifespan of Drosophila, suggesting that sensory perception has an evolutionarily conserved role in lifespan control. These studies highlight the potential of ethosuximide and related drugs that modulate sensory perception to extend lifespan in diverse animals.

  10. Gambling on the Lottery: Sociodemographic Correlates Across the Lifespan

    OpenAIRE

    2011-01-01

    Two representative U.S. telephone surveys of gambling were conducted --an adult survey of adults aged 18 years and older (n = 2,631) and a youth survey of young people aged 14 – 21 years old (n = 2,274). Because the questions and methods were the same or similar in both surveys, the data from these two surveys were combined into a single dataset to examine the prevalence and sociodemographic correlates of gambling and problem gambling across the lifespan. The present work focused specifically...

  11. Folate status of gut microbiome affects Caenorhabditis elegans lifespan

    Directory of Open Access Journals (Sweden)

    Nguyen Theresa PT

    2012-07-01

    Full Text Available Abstract In a paper in BMC Biology Virk et al. show that Caenorhabditis elegans lifespan is extended in response to a diet of folate-deficient Escherichia coli. The deficiencies in folate biosynthesis were due to an aroD mutation, or treatment of E. coli with sulfa drugs, which are mimics of the folate precursor para-aminobenzoic acid. This study suggests that pharmacological manipulation of the gut microbiome folate status may be a viable approach to slow animal aging, and raises questions about folate supplementation. See research article http://www.http://www.biomedcentral.com/1741-7007/10/67

  12. Heat shock factors: integrators of cell stress, development and lifespan.

    Science.gov (United States)

    Akerfelt, Malin; Morimoto, Richard I; Sistonen, Lea

    2010-08-01

    Heat shock factors (HSFs) are essential for all organisms to survive exposures to acute stress. They are best known as inducible transcriptional regulators of genes encoding molecular chaperones and other stress proteins. Four members of the HSF family are also important for normal development and lifespan-enhancing pathways, and the repertoire of HSF targets has thus expanded well beyond the heat shock genes. These unexpected observations have uncovered complex layers of post-translational regulation of HSFs that integrate the metabolic state of the cell with stress biology, and in doing so control fundamental aspects of the health of the proteome and ageing.

  13. Emotional Egocentricity Bias across the life-span

    Directory of Open Access Journals (Sweden)

    Federica eRiva

    2016-04-01

    Full Text Available In our daily lives, we often have to quickly estimate the emotions of our conspecifics in order to have successful social interactions. While this estimation process seems quite easy when we are ourselves in a neutral or equivalent emotional state, it has recently been shown that in case of incongruent emotional states between ourselves and the others, our judgments can be biased. This phenomenon, introduced to the literature with the term Emotional Egocentricity Bias (EEB, has been found to occur in young adults and, to a greater extent, in children. However, how EEB changes across the life-span from adolescence to old age has been largely unexplored. In this study, we recruited 114 female participants subdivided in four cohorts (adolescents, young adults, middle-aged adults, older adults to examine EEB age-related changes. Participants were administered with a paradigm which, by making use of visuo-tactile stimulation that elicits conflicting feelings in paired participants, allows the valid and reliable exploration of EEB. Results highlighted a U-shaped relation between age and EEB, revealing higher emotional egocentricity in adolescents and older adults compared to young and middle-aged adults. These results are in line with the neuroscientific literature which has recently shown that overcoming EEB is associated with a greater activation of a portion of the parietal lobe, namely the right Supramarginal Gyrus (rSMG. This is an area that reaches full maturation only by the end of adolescence, and displays an early decay in older age. Thus, the age-related changes of the EEB could be possibly due to the life-span development of the rSMG. This study is the first one to show the quadratic relation between age and the EEB and set a milestone for further research exploring the neural correlates of the life-span development of the EEB. Future studies are needed in order to generalize these results to the male population and to explore gender

  14. Building lifespan: effect on the environmental impact of building components in a Danish perspective

    DEFF Research Database (Denmark)

    Marsh, Rob

    2017-01-01

    solutions, covering all primary building components and based on contemporary practice. A full statistical analysis is carried out, which shows a significant statistical correlation between changes in building lifespan and environmental impact for all primary building components, except windows....../rooflights. On average, a building lifespan of 80 years reduces environmental impact by 29 %, 100 years by 38 %, and 120 years by 44 %, all in relation to a lifespan of 50 years. The results show that if construction professionals and policy makers use short building lifespans, then resource allocation to reduce...

  15. Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway.

    Science.gov (United States)

    Williams, David S; Cash, Alan; Hamadani, Lara; Diemer, Tanja

    2009-12-01

    Reduced dietary intake increases lifespan in a wide variety of organisms. It also retards disease progression. We tested whether dietary supplementation of citric acid cycle metabolites could mimic this lifespan effect. We report that oxaloacetate supplementation increased lifespan in Caenorhabditis elegans. The increase was dependent on the transcription factor, FOXO/DAF-16, and the energy sensor, AMP-activated protein kinase, indicating involvement of a pathway that is also required for lifespan extension through dietary restriction. These results demonstrate that supplementation of the citric acid cycle metabolite, oxaloacetate, influences a longevity pathway, and suggest a tractable means of introducing the health-related benefits of dietary restriction.

  16. Decreased segregation of brain systems across the healthy adult lifespan.

    Science.gov (United States)

    Chan, Micaela Y; Park, Denise C; Savalia, Neil K; Petersen, Steven E; Wig, Gagan S

    2014-11-18

    Healthy aging has been associated with decreased specialization in brain function. This characterization has focused largely on describing age-accompanied differences in specialization at the level of neurons and brain areas. We expand this work to describe systems-level differences in specialization in a healthy adult lifespan sample (n = 210; 20-89 y). A graph-theoretic framework is used to guide analysis of functional MRI resting-state data and describe systems-level differences in connectivity of individual brain networks. Young adults' brain systems exhibit a balance of within- and between-system correlations that is characteristic of segregated and specialized organization. Increasing age is accompanied by decreasing segregation of brain systems. Compared with systems involved in the processing of sensory input and motor output, systems mediating "associative" operations exhibit a distinct pattern of reductions in segregation across the adult lifespan. Of particular importance, the magnitude of association system segregation is predictive of long-term memory function, independent of an individual's age.

  17. Homeless Aging Veterans in Transition: A Life-Span Perspective

    Directory of Open Access Journals (Sweden)

    Carla J. Thompson

    2013-01-01

    Full Text Available The need for counseling and career/educational services for homeless veterans has captured political and economic venues for more than 25 years. Veterans are three times more likely to become homeless than the general population if veterans live in poverty or are minority veterans. This mixed methods study emphasized a life-span perspective approach for exploring factors influencing normative aging and life-quality of 39 homeless veterans in Alabama and Florida. Seven descriptive quantitative and qualitative research questions framed the investigation. Study participants completed a quantitative survey reflecting their preferences and needs with a subset of the sample (N=12 also participating in individual qualitative interview sessions. Thirty-two service providers and stakeholders completed quantitative surveys. Empirical and qualitative data with appropriate triangulation procedures provided interpretive information relative to a life-span development perspective. Study findings provide evidence of the need for future research efforts to address strategies that focus on the health and economic challenges of veterans before they are threatened with the possibility of homelessness. Implications of the study findings provide important information associated with the premise that human development occurs throughout life with specific characteristics influencing the individual’s passage. Implications for aging/homelessness research are grounded in late-life transitioning and human development intervention considerations.

  18. Sesamin extends the mean lifespan of fruit flies.

    Science.gov (United States)

    Zuo, Yuanyuan; Peng, Cheng; Liang, Yintong; Ma, Ka Ying; Chan, Ho Yin Edwin; Huang, Yu; Chen, Zhen-Yu

    2013-04-01

    The present study investigated the anti-ageing activity of sesamin and its effect on gene expression of superoxide dismutase (SOD), catalase (CAT), methuselah (Mth) and Rpn11 in Drosophila melanogaster. Results demonstrated that 0.2 % sesamin in diet prolonged the mean lifespan of OR wild fruit flies by 12 %, accompanied by up-regulation of SOD1, SOD2, CAT and Rpn11. Sesamin at 0.2 % in diet also attenuated paraquat-induced neurodegeneration with up-regulation of SOD1, SOD2 and Rpn11 in OR wild fruit flies. Supplementation of 0.2 % sesamin in diet increased the survival time of OR wild type flies and Alzheimer flies Aβ42 33769 when they were challenged with paraquat. Furthermore, sesamin-induced increase in the activity and expression of antioxidant enzymes also suggests that the longevity promoting activity of sesamin are possibly due to its action as a hormetin by inducing oxidative stress response-mediated hormesis. It was concluded that sesamin extended the mean lifespan and alleviated the neurodegeneration in Drosophila melanogaster at least mediated by its interaction with genes SOD1, SOD2, CAT, and Rpn11, but not with gene Mth.

  19. Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol.

    Science.gov (United States)

    Morselli, Eugenia; Galluzzi, Lorenzo; Kepp, Oliver; Criollo, Alfredo; Maiuri, Maria Chiara; Tavernarakis, Nektarios; Madeo, Frank; Kroemer, Guido

    2009-12-23

    Although autophagy has widely been conceived as a self-destructive mechanism that causes cell death, accumulating evidence suggests that autophagy usually mediates cytoprotection, thereby avoiding the apoptotic or necrotic demise of stressed cells. Recent evidence produced by our groups demonstrates that autophagy is also involved in pharmacological manipulations that increase longevity. Exogenous supply of the polyamine spermidine can prolong the lifespan of (while inducing autophagy in) yeast, nematodes and flies. Similarly, resveratrol can trigger autophagy in cells from different organisms, extend lifespan in nematodes, and ameliorate the fitness of human cells undergoing metabolic stress. These beneficial effects are lost when essential autophagy modulators are genetically or pharmacologically inactivated, indicating that autophagy is required for the cytoprotective and/or anti-aging effects of spermidine and resveratrol. Genetic and functional studies indicate that spermidine inhibits histone acetylases, while resveratrol activates the histone deacetylase Sirtuin 1 to confer cytoprotection/longevity. Although it remains elusive whether the same histones (or perhaps other nuclear or cytoplasmic proteins) act as the downstream targets of spermidine and resveratrol, these results point to an essential role of protein hypoacetylation in autophagy control and in the regulation of longevity.

  20. Dual systems of speech category learning across the lifespan

    Science.gov (United States)

    Maddox, W. Todd; Chandrasekaran, Bharath; Smayda, Kirsten; Yi, Han-Gyol

    2013-01-01

    Although categorization is fundamental to speech processing, little is known about the learning systems that mediate auditory categorization and even less is known about changes across the lifespan. Vision research supports dual-learning systems that are grounded in neuroscience and are partially-dissociable. The reflective, rule-based system is prefrontally mediated and uses working memory and executive attention to develop and test rules for classifying in an explicit fashion. The reflexive, information-integration system is striatally mediated and operates by implicitly associating perception with actions that lead to reinforcement. We examine the extent to which dual-learning systems mediate auditory and speech learning in younger and older adults. We examined auditory category learning when a rule-based strategy (Experiment 1) or information-integration strategy (Experiment 2) was optimal, and found an age-related rule-based deficit, but intact information-integration learning. Experiment 3 examined natural auditory category learning, and found an age-related performance deficit. Computational modeling suggested that this was due to older adults’ persistent reliance on sub-optimal, uni-dimensional strategies when two-dimensional strategies were optimal. Working memory capacity was also found to be associated with improved rule-based and natural auditory category learning, but not information-integration category learning. These results suggest that dual-learning systems are operative in speech category learning across the lifespan, and that performance deficits, when present are due to deficiencies in frontally-mediated, rule-based processes. PMID:24364408

  1. Metabolome analysis of effect of aspirin on Drosophila lifespan extension.

    Science.gov (United States)

    Song, Chaochun; Zhu, Chenxing; Wu, Qi; Qi, Jiancheng; Gao, Yue; Zhang, Zhichao; Gaur, Uma; Yang, Deying; Fan, Xiaolan; Yang, Mingyao

    2017-09-01

    Effective approaches for drug development involve the repurposing of existing drugs which are already approved by the FDA. Aspirin has been shown to have many health benefits since its discovery as a nonsteroidal anti-inflammatory drug (NSAID) to treat pain and inflammation. Recent experiments demonstrated the longevity effects of aspirin in Drosophila, but its mechanism remains to be explored. In order to elucidate the effects of drug on metabolism, we carried out the metabolic analysis of aspirin-treated flies. The results identified 404 active metabolites in addition to the extended lifespan and improved healthspan in fly. There were 28 metabolites having significant changes between aspirin-treated group and the control group, out of which 22 compounds were found to have detailed information. These compounds are reported to have important functions in energy metabolism, amino sugar metabolism, and urea metabolism, indicating that aspirin might be playing positive roles in the fly's lifespan and healthspan improvement. Because of the conservation of major longevity pathways and mechanisms in different species, the health benefits of aspirin administration could be extended to other animals and humans as well. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Form and Function of Sleep Spindles across the Lifespan

    Directory of Open Access Journals (Sweden)

    Brittany C. Clawson

    2016-01-01

    Full Text Available Since the advent of EEG recordings, sleep spindles have been identified as hallmarks of non-REM sleep. Despite a broad general understanding of mechanisms of spindle generation gleaned from animal studies, the mechanisms underlying certain features of spindles in the human brain, such as “global” versus “local” spindles, are largely unknown. Neither the topography nor the morphology of sleep spindles remains constant throughout the lifespan. It is likely that changes in spindle phenomenology during development and aging are the result of dramatic changes in brain structure and function. Across various developmental windows, spindle activity is correlated with general cognitive aptitude, learning, and memory; however, these correlations vary in strength, and even direction, depending on age and metrics used. Understanding these differences across the lifespan should further clarify how these oscillations are generated and their function under a variety of circumstances. We discuss these issues, and their translational implications for human cognitive function. Because sleep spindles are similarly affected in disorders of neurodevelopment (such as schizophrenia and during aging (such as neurodegenerative conditions, both types of disorders may benefit from therapies based on a better understanding of spindle function.

  3. On the challenge of a century lifespan satellite

    Science.gov (United States)

    Gonzalo, Jesús; Domínguez, Diego; López, Deibi

    2014-10-01

    This paper provides a review of the main issues affecting satellite survivability, including a discussion on the technologies to mitigate the risks and to enhance system reliability. The feasibility of a 100-year lifespan space mission is taken as the guiding thread for the discussion. Such a mission, defined with a few preliminary requirements, could be used to deliver messages to our descendants regardless of the on-ground contingencies. After the analysis of the main threats for long endurance in space, including radiation, debris and micrometeoroids, atmospheric drag and thermal environment, the available solutions are investigated. A trade-off study analyses orbital profiles from the point of view of radiation, thermal stability and decay rate, providing best locations to maximize lifespan. Special attention is also paid to on-board power, in terms of energy harvesting and accumulation, highlighting the limitations of current assets, i.e. solar panels and batteries, and revealing possible future solutions. Furthermore, the review includes electronics, non-volatile memories and communication elements, which need extra hardening against radiation and thermal cycling if extra-long endurance is required. As a result of the analysis, a century-lifetime mission is depicted by putting together all the reviewed concepts. The satellite, equipped with reliability enhanced elements and system-level solutions such as smart hibernation policies, could provide limited but still useful performance after a 100-year flight.

  4. Development of large-scale functional networks over the lifespan.

    Science.gov (United States)

    Schlee, Winfried; Leirer, Vera; Kolassa, Stephan; Thurm, Franka; Elbert, Thomas; Kolassa, Iris-Tatjana

    2012-10-01

    The development of large-scale functional organization of the human brain across the lifespan is not well understood. Here we used magnetoencephalographic recordings of 53 adults (ages 18-89) to characterize functional brain networks in the resting state. Slow frequencies engage larger networks than higher frequencies and show different development over the lifespan. Networks in the delta (2-4 Hz) frequency range decrease, while networks in the beta/gamma frequency range (> 16 Hz) increase in size with advancing age. Results show that the right frontal lobe and the temporal areas in both hemispheres are important relay stations in the expanding high-frequency networks. Neuropsychological tests confirmed the tendency of cognitive decline with older age. The decrease in visual memory and visuoconstructive functions was strongly associated with the age-dependent enhancement of functional connectivity in both temporal lobes. Using functional network analysis this study elucidates important neuronal principles underlying age-related cognitive decline paving mental deterioration in senescence.

  5. C. elegans S6K Mutants Require a Creatine-Kinase-like Effector for Lifespan Extension.

    Science.gov (United States)

    McQuary, Philip R; Liao, Chen-Yu; Chang, Jessica T; Kumsta, Caroline; She, Xingyu; Davis, Andrew; Chu, Chu-Chiao; Gelino, Sara; Gomez-Amaro, Rafael L; Petrascheck, Michael; Brill, Laurence M; Ladiges, Warren C; Kennedy, Brian K; Hansen, Malene

    2016-03-08

    Deficiency of S6 kinase (S6K) extends the lifespan of multiple species, but the underlying mechanisms are unclear. To discover potential effectors of S6K-mediated longevity, we performed a proteomics analysis of long-lived rsks-1/S6K C. elegans mutants compared to wild-type animals. We identified the arginine kinase ARGK-1 as the most significantly enriched protein in rsks-1/S6K mutants. ARGK-1 is an ortholog of mammalian creatine kinase, which maintains cellular ATP levels. We found that argk-1 is possibly a selective effector of rsks-1/S6K-mediated longevity and that overexpression of ARGK-1 extends C. elegans lifespan, in part by activating the energy sensor AAK-2/AMPK. argk-1 is also required for the reduced body size and increased stress resistance observed in rsks-1/S6K mutants. Finally, creatine kinase levels are increased in the brains of S6K1 knockout mice. Our study identifies ARGK-1 as a longevity effector in C. elegans with reduced RSKS-1/S6K levels. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. C. elegans S6K Mutants Require a Creatine-Kinase-like Effector for Lifespan Extension

    Directory of Open Access Journals (Sweden)

    Philip R. McQuary

    2016-03-01

    Full Text Available Deficiency of S6 kinase (S6K extends the lifespan of multiple species, but the underlying mechanisms are unclear. To discover potential effectors of S6K-mediated longevity, we performed a proteomics analysis of long-lived rsks-1/S6K C. elegans mutants compared to wild-type animals. We identified the arginine kinase ARGK-1 as the most significantly enriched protein in rsks-1/S6K mutants. ARGK-1 is an ortholog of mammalian creatine kinase, which maintains cellular ATP levels. We found that argk-1 is possibly a selective effector of rsks-1/S6K-mediated longevity and that overexpression of ARGK-1 extends C. elegans lifespan, in part by activating the energy sensor AAK-2/AMPK. argk-1 is also required for the reduced body size and increased stress resistance observed in rsks-1/S6K mutants. Finally, creatine kinase levels are increased in the brains of S6K1 knockout mice. Our study identifies ARGK-1 as a longevity effector in C. elegans with reduced RSKS-1/S6K levels.

  7. Pheromone sensing regulates Caenorhabditis elegans lifespan and stress resistance via the deacetylase SIR-2.1.

    Science.gov (United States)

    Ludewig, Andreas H; Izrayelit, Yevgeniy; Park, Donha; Malik, Rabia U; Zimmermann, Anna; Mahanti, Parag; Fox, Bennett W; Bethke, Axel; Doering, Frank; Riddle, Donald L; Schroeder, Frank C

    2013-04-02

    Lifespan in Caenorhabditis elegans, Drosophila, and mice is regulated by conserved signaling networks, including the insulin/insulin-like growth factor 1 (IGF-1) signaling cascade and pathways depending on sirtuins, a family of NAD(+)-dependent deacetylases. Small molecules such as resveratrol are of great interest because they increase lifespan in many species in a sirtuin-dependent manner. However, no endogenous small molecules that regulate lifespan via sirtuins have been identified, and the mechanisms underlying sirtuin-dependent longevity are not well understood. Here, we show that in C. elegans, two endogenously produced small molecules, the dauer-inducing ascarosides ascr#2 and ascr#3, regulate lifespan and stress resistance through chemosensory pathways and the sirtuin SIR-2.1. Ascarosides extend adult lifespan and stress resistance without reducing fecundity or feeding rate, and these effects are reduced or abolished when nutrients are restricted. We found that ascaroside-mediated longevity is fully abolished by loss of SIR-2.1 and that the effect of ascr#2 requires expression of the G protein-coupled receptor DAF-37 in specific chemosensory neurons. In contrast to many other lifespan-modulating factors, ascaroside-mediated lifespan increases do not require insulin signaling via the FOXO homolog DAF-16 or the insulin/IGF-1-receptor homolog DAF-2. Our study demonstrates that C. elegans produces specific small molecules to control adult lifespan in a sirtuin-dependent manner, supporting the hypothesis that endogenous regulation of metazoan lifespan functions, in part, via sirtuins. These findings strengthen the link between chemosensory inputs and conserved mechanisms of lifespan regulation in metazoans and suggest a model for communal lifespan regulation in C. elegans.

  8. Integration of Multiple Nutrient Cues and Regulation of Lifespan by Ribosomal Transcription Factor Ifh1

    Directory of Open Access Journals (Sweden)

    Ling Cai

    2013-09-01

    Full Text Available Ribosome biogenesis requires an enormous commitment of energy and resources in growing cells. In budding yeast, the transcriptional coactivator Ifh1p is an essential regulator of ribosomal protein (RP gene transcription. Here, we report that Ifh1p is dynamically acetylated and phosphorylated as a function of the growth state of cells. Ifh1p is acetylated at numerous sites in its N-terminal region by Gcn5p and deacetylated by NAD+-dependent deacetylases of the sirtuin family. Acetylation of Ifh1p is responsive to intracellular acetyl-CoA levels and serves to regulate the stability of Ifh1p. The phosphorylation of Ifh1p is mediated by protein kinase A and is dependent on TORC1 signaling. Thus, multiple nutrient-sensing mechanisms converge on Ifh1p. However, instead of modulating overall rates of RP gene transcription or cell growth, the nutrient-responsive phosphorylation of Ifh1p plays a more prominent role in the regulation of cellular replicative lifespan.

  9. Novel protein kinase signaling systems regulating lifespan identified by small molecule library screening using Drosophila.

    Directory of Open Access Journals (Sweden)

    Stephen R Spindler

    Full Text Available Protein kinase signaling cascades control most aspects of cellular function. The ATP binding domains of signaling protein kinases are the targets of most available inhibitors. These domains are highly conserved from mammals to flies. Herein we describe screening of a library of small molecule inhibitors of protein kinases for their ability to increase Drosophila lifespan. We developed an assay system which allowed screening using the small amounts of materials normally present in commercial chemical libraries. The studies identified 17 inhibitors, the majority of which targeted tyrosine kinases associated with the epidermal growth factor receptor (EGFR, platelet-derived growth factor (PDGF/vascular endothelial growth factor (VEGF receptors, G-protein coupled receptor (GPCR, Janus kinase (JAK/signal transducer and activator of transcription (STAT, the insulin and insulin-like growth factor (IGFI receptors. Comparison of the protein kinase signaling effects of the inhibitors in vitro defined a consensus intracellular signaling profile which included decreased signaling by p38MAPK (p38, c-Jun N-terminal kinase (JNK and protein kinase C (PKC. If confirmed, many of these kinases will be novel additions to the signaling cascades known to regulate metazoan longevity.

  10. Novel protein kinase signaling systems regulating lifespan identified by small molecule library screening using Drosophila.

    Science.gov (United States)

    Spindler, Stephen R; Li, Rui; Dhahbi, Joseph M; Yamakawa, Amy; Sauer, Frank

    2012-01-01

    Protein kinase signaling cascades control most aspects of cellular function. The ATP binding domains of signaling protein kinases are the targets of most available inhibitors. These domains are highly conserved from mammals to flies. Herein we describe screening of a library of small molecule inhibitors of protein kinases for their ability to increase Drosophila lifespan. We developed an assay system which allowed screening using the small amounts of materials normally present in commercial chemical libraries. The studies identified 17 inhibitors, the majority of which targeted tyrosine kinases associated with the epidermal growth factor receptor (EGFR), platelet-derived growth factor (PDGF)/vascular endothelial growth factor (VEGF) receptors, G-protein coupled receptor (GPCR), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), the insulin and insulin-like growth factor (IGFI) receptors. Comparison of the protein kinase signaling effects of the inhibitors in vitro defined a consensus intracellular signaling profile which included decreased signaling by p38MAPK (p38), c-Jun N-terminal kinase (JNK) and protein kinase C (PKC). If confirmed, many of these kinases will be novel additions to the signaling cascades known to regulate metazoan longevity.

  11. Specific protein homeostatic functions of small heat-shock proteins increase lifespan.

    Science.gov (United States)

    Vos, Michel J; Carra, Serena; Kanon, Bart; Bosveld, Floris; Klauke, Karin; Sibon, Ody C M; Kampinga, Harm H

    2016-04-01

    During aging, oxidized, misfolded, and aggregated proteins accumulate in cells, while the capacity to deal with protein damage declines severely. To cope with the toxicity of damaged proteins, cells rely on protein quality control networks, in particular proteins belonging to the family of heat-shock proteins (HSPs). As safeguards of the cellular proteome, HSPs assist in protein folding and prevent accumulation of damaged, misfolded proteins. Here, we compared the capacity of all Drosophila melanogaster small HSP family members for their ability to assist in refolding stress-denatured substrates and/or to prevent aggregation of disease-associated misfolded proteins. We identified CG14207 as a novel and potent small HSP member that exclusively assisted in HSP70-dependent refolding of stress-denatured proteins. Furthermore, we report that HSP67BC, which has no role in protein refolding, was the most effective small HSP preventing toxic protein aggregation in an HSP70-independent manner. Importantly, overexpression of both CG14207 and HSP67BC in Drosophila leads to a mild increase in lifespan, demonstrating that increased levels of functionally diverse small HSPs can promote longevity in vivo.

  12. An intricate dance: Life experience, multisystem resiliency, and rate of telomere decline throughout the lifespan.

    Science.gov (United States)

    Puterman, Eli; Epel, Elissa

    2012-11-01

    Accumulation of life stressors predicts accelerated development and progression of diseases of aging. Telomere length, the DNA-based biomarker indicating cellular aging, is a mechanism of disease development, and is shortened in a dose response fashion by duration and severity of life stressor exposures. Telomere length captures the interplay between genetics, life experiences and psychosocial and behavioral factors. Over the past several years, psychological stress resilience, healthy lifestyle factors, and social connections have been associated with longer telomere length and it appears that these factors can protect individuals from stress-induced telomere shortening. In the current review, we highlight these findings, and illustrate that combining these `multisystem resiliency' factors may strengthen our understanding of aging, as these powerful factors are often neglected in studies of aging. In naturalistic studies, the effects of chronic stress exposure on biological pathways are rarely main effects, but rather a complex interplay between adversity and resiliency factors. We suggest that chronic stress effects can be best understood by directly testing if the deleterious effects of stress on biological aging processes, in this case the cell allostasis measure of telomere shortening, are mitigated in individuals with high levels of multisystem resiliency. Without attending to such interactions, stress effects are often masked and missed. Taking account of the cluster of positive buffering factors that operate across the lifespan will take us a step further in understanding healthy aging. While these ideas are applied to the telomere length literature for illustration, the concept of multisystem resiliency might apply to aging broadly, from cellular to systemic health.

  13. Curcumin-supplemented diets increase superoxide dismutase activity and mean lifespan in Drosophila

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    Curcumin is an antioxidant extracted from the root of the turmeric plant. We examined the antioxidant effect and lifespan extension of curcumin in Drosophila. To ascertain the antioxidant effects of curcumin with regard to lifespan extension and the response to reactive oxygen species, female and ma...

  14. Why do lifespan variability trends for the young and old diverge? A perturbation analysis

    NARCIS (Netherlands)

    Engelman, M.; Caswell, H.; Agree, E.M.

    2013-01-01

    Background: Variation in lifespan has followed strikingly different trends for the young and old: while overall lifespan variability has decreased as life expectancy at birth has risen, the variability conditional on survival to older ages has increased. These diverging trends reflect changes in the

  15. Target of rapamycin signaling regulates metabolism, growth, and lifespan in Arabidopsis

    Science.gov (United States)

    TOR is a major nutrition and energy sensor that regulates growth and lifespan in yeast and animals. In plants growth and lifespan are intertwined with not only nutrient acquisition but also nutrition generation and unique aspects of development and differentiation. How TOR functions in these process...

  16. Coherence of Personal Narratives across the Lifespan: A Multidimensional Model and Coding Method

    Science.gov (United States)

    Reese, Elaine; Haden, Catherine A.; Baker-Ward, Lynne; Bauer, Patricia; Fivush, Robyn; Ornstein, Peter A.

    2011-01-01

    Personal narratives are integral to autobiographical memory and to identity, with coherent personal narratives being linked to positive developmental outcomes across the lifespan. In this article, we review the theoretical and empirical literature that sets the stage for a new lifespan model of personal narrative coherence. This new model…

  17. No influence of Indy on lifespan in Drosophila after correction for genetic and cytoplasmic background effects.

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    Janne M Toivonen

    2007-06-01

    Full Text Available To investigate whether alterations in mitochondrial metabolism affect longevity in Drosophila melanogaster, we studied lifespan in various single gene mutants, using inbred and outbred genetic backgrounds. As positive controls we included the two most intensively studied mutants of Indy, which encodes a Drosophila Krebs cycle intermediate transporter. It has been reported that flies heterozygous for these Indy mutations, which lie outside the coding region, show almost a doubling of lifespan. We report that only one of the two mutants lowers mRNA levels, implying that the lifespan extension observed is not attributable to the Indy mutations themselves. Moreover, neither Indy mutation extended lifespan in female flies in any genetic background tested. In the original genetic background, only the Indy mutation associated with altered RNA expression extended lifespan in male flies. However, this effect was abolished by backcrossing into standard outbred genetic backgrounds, and was associated with an unidentified locus on the X chromosome. The original Indy line with long-lived males is infected by the cytoplasmic symbiont Wolbachia, and the longevity of Indy males disappeared after tetracycline clearance of this endosymbiont. These findings underscore the critical importance of standardisation of genetic background and of cytoplasm in genetic studies of lifespan, and show that the lifespan extension previously claimed for Indy mutants was entirely attributable to confounding variation from these two sources. In addition, we saw no effects on lifespan of expression knockdown of the Indy orthologues nac-2 and nac-3 in the nematode Caenorhabditis elegans.

  18. Electrophysiological correlates of selective attention: A lifespan comparison

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    von Oertzen Timo

    2008-01-01

    Full Text Available Abstract Background To study how event-related brain potentials (ERPs and underlying cortical mechanisms of selective attention change from childhood to old age, we investigated lifespan age differences in ERPs during an auditory oddball task in four age groups including 24 younger children (9–10 years, 28 older children (11–12 years, 31 younger adults (18–25, and 28 older adults (63–74 years. In the Unattend condition, participants were asked to simply listen to the tones. In the Attend condition, participants were asked to count the deviant stimuli. Five primary ERP components (N1, P2, N2, P3 and N3 were extracted for deviant stimuli under Attend conditions for lifespan comparison. Furthermore, Mismatch Negativity (MMN and Late Discriminative Negativity (LDN were computed as difference waves between deviant and standard tones, whereas Early and Late Processing Negativity (EPN and LPN were calculated as difference waves between tones processed under Attend and Unattend conditions. These four secondary ERP-derived measures were taken as indicators for change detection (MMN and LDN and selective attention (EPN and LPN, respectively. To examine lifespan age differences, the derived difference-wave components for attended (MMN and LDN and deviant (EPN and LPN stimuli were specifically compared across the four age groups. Results Both primary and secondary ERP components showed age-related differences in peak amplitude, peak latency, and topological distribution. The P2 amplitude was higher in adults compared to children, whereas N2 showed the opposite effect. P3 peak amplitude was higher in older children and younger adults than in older adults. The amplitudes of N3, LDN, and LPN were higher in older children compared with both of the adult groups. In addition, both P3 and N3 peak latencies were significantly longer in older than in younger adults. Interestingly, in the young adult sample P3 peak amplitude correlated positively and P3 peak

  19. Emotional Egocentricity Bias Across the Life-Span.

    Science.gov (United States)

    Riva, Federica; Triscoli, Chantal; Lamm, Claus; Carnaghi, Andrea; Silani, Giorgia

    2016-01-01

    In our daily lives, we often have to quickly estimate the emotions of our conspecifics in order to have successful social interactions. While this estimation process seems quite easy when we are ourselves in a neutral or equivalent emotional state, it has recently been shown that in case of incongruent emotional states between ourselves and the others, our judgments can be biased. This phenomenon, introduced to the literature with the term Emotional Egocentricity Bias (EEB), has been found to occur in young adults and, to a greater extent, in children. However, how the EEB changes across the life-span from adolescence to old age has been largely unexplored. In this study, we recruited 114 female participants subdivided in four cohorts (adolescents, young adults, middle-aged adults, older adults) to examine EEB age-related changes. Participants were administered with a recently developed paradigm which, by making use of visuo-tactile stimulation that elicits conflicting feelings in paired participants, allows the valid and reliable exploration of the EEB. Results highlighted a U-shape relation between age and EEB, revealing enhanced emotional egocentricity in adolescents and older adults compared to young and middle-aged adults. These results are in line with the neuroscientific literature which has recently shown that overcoming the EEB is associated with a greater activation of a portion of the parietal lobe, namely the right Supramarginal Gyrus (rSMG). This is an area that reaches full maturation by the end of adolescence and goes through an early decay. Thus, the age-related changes of the EEB could be possibly due to the life-span development of the rSMG. This study is the first one to show the quadratic relation between age and the EEB and set a milestone for further research exploring the neural correlates of the life-span development of the EEB. Future studies are needed in order to generalize these results to the male population and to explore gender

  20. Ontogenetic patterns in the dreams of women across the lifespan.

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    Dale, Allyson; Lortie-Lussier, Monique; De Koninck, Joseph

    2015-12-01

    The present study supports and extends previous research on the developmental differences in women's dreams across the lifespan. The participants included 75 Canadian women in each of 5 age groups from adolescence to old age including 12-17, 18-24, 25-39, 40-64, and 65-85, totaling 375 women. One dream per participant was scored by two independent judges using the method of content analysis. Trend analysis was used to determine the ontogenetic pattern of the dream content categories. Results demonstrated significant ontogenetic decreases (linear trends) for female and familiar characters, activities, aggression, and friendliness. These patterns of dream imagery reflect the waking developmental patterns as proposed by social theories and recognized features of aging as postulated by the continuity hypothesis. Limitations and suggestions for future research including the examining of developmental patterns in the dreams of males are discussed.

  1. Linguistic Processing of Accented Speech Across the Lifespan

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    Alejandrina eCristia

    2012-11-01

    Full Text Available In most of the world, people have regular exposure to multiple accents. Therefore, learning to quickly process accented speech is a prerequisite to successful communication. In this paper, we examine work on the perception of accented speech across the lifespan, from early infancy to late adulthood. Unfamiliar accents initially impair linguistic processing by infants, children, younger adults, and older adults, but listeners of all ages come to adapt to accented speech. Emergent research also goes beyond these perceptual abilities, by assessing links with production and the relative contributions of linguistic knowledge and general cognitive skills. We conclude by underlining points of convergence across ages, and the gaps left to face in future work.

  2. Exercise, APOE genotype, and the evolution of the human lifespan

    Science.gov (United States)

    Raichlen, David A.; Alexander, Gene E.

    2014-01-01

    Humans have exceptionally long lifespans compared with other mammals. However, our longevity evolved when our ancestors had two copies of the apolipoprotein E (APOE) ε4 allele, a genotype that leads to a high risk of Alzheimer’s disease (AD), cardiovascular disease, and increased mortality. How did human aging evolve within this genetic constraint? Drawing from neuroscience, anthropology, and brain-imaging research, we propose the hypothesis that the evolution of increased physical activity approximately 2 million years ago served to reduce the amyloid plaque and vascular burden of APOE ε4, relaxing genetic constraints on aging. This multidisciplinary approach links human evolution with health and provides a complementary perspective on aging and neurodegenerative disease that may help identify key mechanisms and targets for intervention. PMID:24690272

  3. Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years.

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    Rolf Knoth

    Full Text Available BACKGROUND: Essentially all knowledge about adult hippocampal neurogenesis in humans still comes from one seminal study by Eriksson et al. in 1998, although several others have provided suggestive findings. But only little information has been available in how far the situation in animal models would reflect the conditions in the adult and aging human brain. We therefore here mapped numerous features associated with adult neurogenesis in rodents in samples from human hippocampus across the entire lifespan. Such data would not offer proof of adult neurogenesis in humans, because it is based on the assumption that humans and rodents share marker expression patterns in adult neurogenesis. Nevertheless, together the data provide valuable information at least about the presence of markers, for which a link to adult neurogenesis might more reasonably be assumed than for others, in the adult human brain and their change with increasing age. METHODS AND FINDINGS: In rodents, doublecortin (DCX is transiently expressed during adult neurogenesis and within the neurogenic niche of the dentate gyrus can serve as a valuable marker. We validated DCX as marker of granule cell development in fetal human tissue and used DCX expression as seed to examine the dentate gyrus for additional neurogenesis-associated features across the lifespan. We studied 54 individuals and detected DCX expression between birth and 100 years of age. Caveats for post-mortem analyses of human tissues apply but all samples were free of signs of ischemia and activated caspase-3. Fourteen markers related to adult hippocampal neurogenesis in rodents were assessed in DCX-positive cells. Total numbers of DCX expressing cells declined exponentially with increasing age, and co-expression of DCX with the other markers decreased. This argued against a non-specific re-appearance of immature markers in specimen from old brains. Early postnatally all 14 markers were co-expressed in DCX-positive cells

  4. The Cost of Mating: Influences of Life History Traits and Mating Strategies on Lifespan in Two Closely Related Yponomeuta Species

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    A. C. Bakker

    2011-01-01

    Full Text Available Theory predicts that in monandrous butterfly species males should not invest in a long lifespan because receptive females quickly disappear from the mating population. In polyandrous species, however, it pays for males to invest in longevity, which increases the number of mating opportunities and thus reproductive fitness. We tested an extension of this idea and compared male and female lifespan of two closely related Yponomeuta species with different degree of polyandry. Our results confirmed the theoretical prediction that male lifespan is fine-tuned to female receptive lifespan; once-mated males and females of both polyandrous species had an equal lifespan. However, the degree of polyandry was not reflected in male relative to female lifespan. The observed similar female and male lifespan could largely be attributed to a dramatic reduction of female lifespan after mating.

  5. Why do lifespan variability trends for the young and old diverge? A perturbation analysis

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    Michal Engelman

    2014-05-01

    Full Text Available Background: Variation in lifespan has followed strikingly different trends for the young and old: while overall lifespan variability has decreased as life expectancy at birth has risen, the variability conditional on survival to older ages has increased. These diverging trends reflect changes in the underlying demographic parameters determining age-specific mortality. Objective: We ask why the variation in the adult ages at death has followed a different trend than the variation at younger ages, and aim to explain the diverging patterns in terms of historical changes in the age schedule of mortality. Methods: Using simulations, we show that the empirical trends in lifespan variation are well characterized using the Siler model, which describes the mortality hazard across the full lifespan using functions representing early-life, later-life, and background mortality. We then obtain maximum likelihood estimates of the Siler parameters over time. Finally, we express lifespan variation in terms of a Markov chain model, and apply matrix calculus perturbation analysis to compute the sensitivity of age-specific lifespan variance trends to the changing Siler model parameters. Results: Our analysis produces a detailed quantification of the impact of changing demographic parameters on the pattern of lifespan variability at all ages, highlighting the impact of declining childhood mortality on the reduction of lifespan variability and the impact of improved survival in adulthood on the rising variability of lifespans at older ages. Conclusions: These findings provide insight into the dynamic relationship between the age pattern of survival improvements and time trends in lifespan variability.

  6. HIF-1 modulates dietary restriction-mediated lifespan extension via IRE-1 in Caenorhabditis elegans.

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    Di Chen

    2009-05-01

    Full Text Available Dietary restriction (DR extends lifespan in various species and also slows the onset of age-related diseases. Previous studies from flies and yeast have demonstrated that the target of rapamycin (TOR pathway is essential for longevity phenotypes resulting from DR. TOR is a conserved protein kinase that regulates growth and metabolism in response to nutrients and growth factors. While some of the downstream targets of TOR have been implicated in regulating lifespan, it is still unclear whether additional targets of this pathway also modulate lifespan. It has been shown that the hypoxia inducible factor-1 (HIF-1 is one of the targets of the TOR pathway in mammalian cells. HIF-1 is a transcription factor complex that plays key roles in oxygen homeostasis, tumor formation, glucose metabolism, cell survival, and inflammatory response. Here, we describe a novel role for HIF-1 in modulating lifespan extension by DR in Caenorhabditis elegans. We find that HIF-1 deficiency results in extended lifespan, which overlaps with that by inhibition of the RSKS-1/S6 kinase, a key component of the TOR pathway. Using a modified DR method based on variation of bacterial food concentrations on solid agar plates, we find that HIF-1 modulates longevity in a nutrient-dependent manner. The hif-1 loss-of-function mutant extends lifespan under rich nutrient conditions but fails to show lifespan extension under DR. Conversely, a mutation in egl-9, which increases HIF-1 activity, diminishes the lifespan extension under DR. This deficiency is rescued by tissue-specific expression of egl-9 in specific neurons and muscles. Increased lifespan by hif-1 or DR is dependent on the endoplasmic reticulum (ER stress regulator inositol-requiring protein-1 (IRE-1 and is associated with lower levels of ER stress. Therefore, our results demonstrate a tissue-specific role for HIF-1 in the lifespan extension by DR involving the IRE-1 ER stress pathway.

  7. Adipocyte insulin receptor activity maintains adipose tissue mass and lifespan.

    Science.gov (United States)

    Friesen, Max; Hudak, Carolyn S; Warren, Curtis R; Xia, Fang; Cowan, Chad A

    2016-08-05

    Type 2 diabetes follows a well-defined progressive pathogenesis, beginning with insulin resistance in metabolic tissues such as the adipose. Intracellular signaling downstream of insulin receptor activation regulates critical metabolic functions of adipose tissue, including glucose uptake, lipogenesis, lipolysis and adipokine secretion. Previous studies have used the aP2 promoter to drive Cre recombinase expression in adipose tissue. Insulin receptor (IR) knockout mice created using this aP2-Cre strategy (FIRKO mice) were protected from obesity and glucose intolerance. Later studies demonstrated the promiscuity of the aP2 promoter, casting doubts upon the tissue specificity of aP2-Cre models. It is our goal to use the increased precision of the Adipoq promoter to investigate adipocyte-specific IR function. Towards this end we generated an adipocyte-specific IR knockout (AIRKO) mouse using an Adipoq-driven Cre recombinase. Here we report AIRKO mice are less insulin sensitive throughout life, and less glucose tolerant than wild-type (WT) littermates at the age of 16 weeks. In contrast to WT littermates, the insulin sensitivity of AIRKO mice is unaffected by age or dietary regimen. At any age, AIRKO mice are comparably insulin resistant to old or obese WT mice and have a significantly reduced lifespan. Similar results were obtained when these phenotypes were re-examined in FIRKO mice. We also found that the AIRKO mouse is protected from high-fat diet-induced weight gain, corresponding with a 90% reduction in tissue weight of major adipose depots compared to WT littermates. Adipose tissue mass reduction is accompanied by hepatomegaly and increased hepatic steatosis. These data indicate that adipocyte IR function is crucial to systemic energy metabolism and has profound effects on adiposity, hepatic homeostasis and lifespan. Copyright © 2016. Published by Elsevier Inc.

  8. Organic fertilization leads to increased peach root production and lifespan.

    Science.gov (United States)

    Baldi, E; Toselli, M; Eissenstat, D M; Marangoni, B

    2010-11-01

    We evaluated the effects of mineral and organic fertilizers on peach root dynamics in the growing season from 2003 to 2006 in a nectarine (Prunus persica L.) orchard, planted in 2001 and located in the Po valley, northeastern Italy. Very few studies have conducted long-term investigations of root dynamics of fruit crops. Our main objective was to determine whether organic fertilizers affect root dynamics differently than mineral fertilizers. The experiment was a completely randomized block design with four replicates of three treatments: unfertilized, mineral fertilized and composted with municipal waste. Mineral fertilizers included P (100 kg ha(-1) year(-1)) and K (200 kg ha(-1) year(-1)) applied only at planting and N (70-130 kg ha(-1) year(-1)) split into two applications, one at 40 days after full bloom (60%) and the other in September (40%) each year. The compost fertilization represented a yearly rate of 10 metric tons (t) dry weight ha(-1), which approximates (in kg ha(-1) year(-1)) 240 N, 100 P and 200 K, split similarly to that described for the mineral fertilization of N. Both root growth and survival were evaluated at 20-day intervals during the growing season by the minirhizotron technique. Compost increased the production of new roots compared with the other treatments (P fertilized or unfertilized trees (P fertilization could be accounted for by variation in soil nitrate concentration as indicated by no effect of fertilizer treatment on root lifespan when soil nitrate was included as a covariate. These results reveal how shifting from mineral to organic fertilizers may shift both soil properties and nutrient availability, leading to changes in both root production and lifespan.

  9. The evolution of senescence and post-reproductive lifespan in guppies (Poecilia reticulata.

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    David Reznick

    2006-01-01

    Full Text Available The study of post-reproductive lifespan has been of interest primarily with regard to the extended post-menopausal lifespan seen in humans. This unusual feature of human demography has been hypothesized to have evolved because of the "grandmother" effect, or the contributions that post-reproductive females make to the fitness of their children and grandchildren. While some correlative analyses of human populations support this hypothesis, few formal, experimental studies have addressed the evolution of post-reproductive lifespan. As part of an ongoing study of life history evolution in guppies, we compared lifespans of individual guppies derived from populations that differ in their extrinsic mortality rates. Some of these populations co-occur with predators that increase mortality rate, whereas other nearby populations above barrier waterfalls are relatively free from predation. Theory predicts that such differences in extrinsic mortality will select for differences in the age at maturity, allocation of resources to reproduction, and patterns of senescence, including reproductive declines. As part of our evaluation of these predictions, we quantified differences among populations in post-reproductive lifespan. We present here the first formal, comparative study of the evolution of post-reproductive lifespan as a component of the evolution of the entire life history. Guppies that evolved with predators and that experienced high extrinsic mortality mature at an earlier age but also have longer lifespans. We divided the lifespan into three non-overlapping components: birth to age at first reproduction, age at first reproduction to age at last reproduction (reproductive lifespan, and age at last reproduction to age at death (post-reproductive lifespan. Guppies from high-predation environments live longer because they have a longer reproductive lifespan, which is the component of the life history that can make a direct contribution to individual

  10. Green tea polyphenols require the mitochondrial iron transporter, mitoferrin, for lifespan extension in Drosophila melanogaster.

    Science.gov (United States)

    Lopez, Terry E; Pham, Hoang M; Nguyen, Benjamin V; Tahmasian, Yerazik; Ramsden, Shannon; Coskun, Volkan; Schriner, Samuel E; Jafari, Mahtab

    2016-12-01

    Green tea has been found to increase the lifespan of various experimental animal models including the fruit fly, Drosophila melanogaster. High in polyphenolic content, green tea has been shown to reduce oxidative stress in part by its ability to bind free iron, a micronutrient that is both essential for and toxic to all living organisms. Due to green tea's iron-binding properties, we questioned whether green tea acts to increase the lifespan of the fruit fly by modulating iron regulators, specifically, mitoferrin, a mitochondrial iron transporter, and transferrin, found in the hemolymph of flies. Publicly available hypomorph mutants for these iron regulators were utilized to investigate the effect of green tea on lifespan and fertility. We identified that green tea could not increase the lifespan of mitoferrin mutants but did rescue the reduced male fertility phenotype. The effect of green tea on transferrin mutant lifespan and fertility were comparable to w(1118) flies, as observed in our previous studies, in which green tea increased male fly lifespan and reduced male fertility. Expression levels in both w(1118) flies and mutant flies, supplemented with green tea, showed an upregulation of mitoferrin but not transferrin. Total body and mitochondrial iron levels were significantly reduced by green tea supplementation in w(1118) and mitoferrin mutants but not transferrin mutant flies. Our results demonstrate that green tea may act to increase the lifespan of Drosophila in part by the regulation of mitoferrin and reduction of mitochondrial iron. © 2016 Wiley Periodicals, Inc.

  11. Sorbitol treatment extends lifespan and induces the osmotic stress response in Caenorhabditis elegans

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    Devon eChandler-Brown

    2015-10-01

    Full Text Available The response to osmotic stress is a highly conserved process for adapting to changing environmental conditions. Prior studies have shown that hyperosmolarity by addition of sorbitol to the growth medium is sufficient to increase both chronological and replicative lifespan in the budding yeast, Saccharomyces cerevisiae. Here we report a similar phenomenon in the nematode Caenorhabditis elegans. Addition of sorbitol to the nematode growth medium induces an adaptive osmotic response and increases C. elegans lifespan by about 35%. Lifespan extension from 5% sorbitol behaves similarly to dietary restriction in a variety of genetic backgrounds, increasing lifespan additively with mutation of daf-2(e1370 and independently of daf-16(mu86, sir-2.1(ok434, aak-2(ok524, and hif-1(ia04. Dietary restriction by bacterial deprivation or mutation of eat-2(ad1113 fails to further extend lifespan in the presence of 5% sorbitol. Two mutants with constitutive activation of the osmotic response, osm-5(p813 and osm-7(n1515, were found to be long-lived, and lifespan extension from sorbitol required the glycerol biosynthetic enzymes GPDH-1 and GPDH-2. Taken together, these observations demonstrate that exposure to sorbitol at levels sufficient to induce an adaptive osmotic response extends lifespan in worms and define the osmotic stress response pathway as a longevity pathway conserved between yeast and nematodes.

  12. Sorbitol treatment extends lifespan and induces the osmotic stress response in Caenorhabditis elegans.

    Science.gov (United States)

    Chandler-Brown, Devon; Choi, Haeri; Park, Shirley; Ocampo, Billie R; Chen, Shiwen; Le, Anna; Sutphin, George L; Shamieh, Lara S; Smith, Erica D; Kaeberlein, Matt

    2015-01-01

    The response to osmotic stress is a highly conserved process for adapting to changing environmental conditions. Prior studies have shown that hyperosmolarity by addition of sorbitol to the growth medium is sufficient to increase both chronological and replicative lifespan in the budding yeast, Saccharomyces cerevisiae. Here we report a similar phenomenon in the nematode Caenorhabditis elegans. Addition of sorbitol to the nematode growth medium induces an adaptive osmotic response and increases C. elegans lifespan by about 35%. Lifespan extension from 5% sorbitol behaves similarly to dietary restriction in a variety of genetic backgrounds, increasing lifespan additively with mutation of daf-2(e1370) and independently of daf-16(mu86), sir-2.1(ok434), aak-2(ok524), and hif-1(ia04). Dietary restriction by bacterial deprivation or mutation of eat-2(ad1113) fails to further extend lifespan in the presence of 5% sorbitol. Two mutants with constitutive activation of the osmotic response, osm-5(p813) and osm-7(n1515), were found to be long-lived, and lifespan extension from sorbitol required the glycerol biosynthetic enzymes GPDH-1 and GPDH-2. Taken together, these observations demonstrate that exposure to sorbitol at levels sufficient to induce an adaptive osmotic response extends lifespan in worms and define the osmotic stress response pathway as a longevity pathway conserved between yeast and nematodes.

  13. Entropy Generation and Human Aging: Lifespan Entropy and Effect of Diet Composition and Caloric Restriction Diets

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    Carlos A. Silva

    2009-01-01

    Full Text Available The first and second laws of thermodynamic were applied to statistical databases on nutrition and human growth in order to estimate the entropy generation over the human lifespan. The calculations were performed for the cases of variation in the diet composition and calorie restriction diets; and results were compared to a base case in which lifespan entropy generation was found to be 11 404 kJ/K per kg of body mass, predicting a lifespan of 73.78 and 81.61 years for the average male and female individuals respectively. From the analysis of the results, it was found that changes of diet % of fat and carbohydrates do not have a significant impact on predicted lifespan, while the diet % of proteins has an important effect. Reduction of diet protein % to the minimum recommended in nutrition literature yields an average increase of 3.3 years on the predicted lifespan. Changes in the calorie content of the diet also have an important effect, yielding a % increase in lifespan equal or higher than the % reduction in the diet caloric content. This correlates well experimental data on small mammal and insects, in which lifespan has been increased by diet restriction.

  14. Differential effects of resveratrol and SRT1720 on lifespan of adult Caenorhabditis elegans.

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    Zarse, K; Schmeisser, S; Birringer, M; Falk, E; Schmoll, D; Ristow, M

    2010-11-01

    Resveratrol and SRT1720 have been shown to act as sirtuin activators that may ameliorate type 2 diabetes and metabolic diseases in mice. Moreover, resveratrol extends lifespan in model organisms like C. elegans, N. FURZERI, and possibly D. melanogaster. The aim of the study was to test whether pharmacological concentrations of resveratrol and SRT1720 are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Several hundreds of adult C. ELEGANS roundworms were maintained on agar plates and fed E. COLI strain OP50 bacteria. Resveratrol (5 micromolar, 500 nanomolar) or SRT1720 (1 micromolar, 100 nanomolar) was applied to the agar to test whether they may promote longevity by quantifying survival in the presence and absence of the respective compounds. At a dose of 5 micromolar, which is pharmacologically relevant and 20 times lower than previously published concentrations, resveratrol significantly extends C. elegans lifespan by 3.6% (mean lifespan) and 3.4% (maximum lifespan). By unexpected contrast, SRT1720, which was previously proposed to be several hundred times more active than resveratrol, did not extend lifespan at none of the concentrations tested. Thus, in the model organisms C. elegans, resveratrol is capable of promoting longevity at a concentration that pharmacologically relevant and 20 times lower than previously published doses. The sirtuin activator SRT1720 did not extend lifespan, suggesting that in C. elegans, some relevant effects of resveratrol cannot be mimicked by SRT1720.

  15. Lifespan and oxidative stress show a non-linear response to atmospheric oxygen in Drosophila.

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    Rascón, Brenda; Harrison, Jon F

    2010-10-15

    Oxygen provides the substrate for most ATP production, but also serves as a source of reactive oxygen species (ROS), which can induce cumulative macromolecular oxidative damage and cause aging. Pure oxygen atmospheres (100 kPa) are known to strongly reduce invertebrate lifespan and induce aging-related physiological changes. However, the nature of the relationship between atmospheric oxygen, oxidative stress, and lifespan across a range of oxygen levels is poorly known. Developmental responses are likely to play a strong role, as prior research has shown strong effects of rearing oxygen level on growth, size and respiratory system morphology. In this study, we examined (1) the effect of oxygen on adult longevity and (2) the effect of the oxygen concentration experienced by larvae on adult lifespan by rearing Drosophila melanogaster in three oxygen atmospheres throughout larval development (10, 21 and 40 kPa), then measuring the lifespan of adults in five oxygen tensions (2, 10, 21, 40, 100 kPa). We also assessed the rate of protein carbonyl production for flies kept at 2, 10, 21, 40 and 100 kPa as adults (all larvae reared in normoxia). The rearing of juveniles in varying oxygen treatments affected lifespan in a complex manner, and the effect of different oxygen tensions on adult lifespan was non-linear, with reduced longevity and heightened oxidative stress at extreme high and low atmospheric oxygen levels. Moderate hypoxia (10 kPa) extended maximum, but not mean lifespan.

  16. A comparative cellular and molecular biology of longevity database.

    Science.gov (United States)

    Stuart, Jeffrey A; Liang, Ping; Luo, Xuemei; Page, Melissa M; Gallagher, Emily J; Christoff, Casey A; Robb, Ellen L

    2013-10-01

    Discovering key cellular and molecular traits that promote longevity is a major goal of aging and longevity research. One experimental strategy is to determine which traits have been selected during the evolution of longevity in naturally long-lived animal species. This comparative approach has been applied to lifespan research for nearly four decades, yielding hundreds of datasets describing aspects of cell and molecular biology hypothesized to relate to animal longevity. Here, we introduce a Comparative Cellular and Molecular Biology of Longevity Database, available at ( http://genomics.brocku.ca/ccmbl/ ), as a compendium of comparative cell and molecular data presented in the context of longevity. This open access database will facilitate the meta-analysis of amalgamated datasets using standardized maximum lifespan (MLSP) data (from AnAge). The first edition contains over 800 data records describing experimental measurements of cellular stress resistance, reactive oxygen species metabolism, membrane composition, protein homeostasis, and genome homeostasis as they relate to vertebrate species MLSP. The purpose of this review is to introduce the database and briefly demonstrate its use in the meta-analysis of combined datasets.

  17. Modulation of Replicative Lifespan in Cryptococcus neoformans: Implications for Virulence

    Science.gov (United States)

    Bouklas, Tejas; Jain, Neena; Fries, Bettina C.

    2017-01-01

    The fungal pathogen, Cryptococcus neoformans, has been shown to undergo replicative aging. Old cells are characterized by advanced generational age and phenotypic changes that appear to mediate enhanced resistance to host and antifungal-based killing. As a consequence of this age-associated resilience, old cells accumulate during chronic infection. Based on these findings, we hypothesized that shifting the generational age of a pathogenic yeast population would alter its vulnerability to the host and affect its virulence. SIR2 is a well-conserved histone deacetylase, and a pivotal target for the development of anti-aging drugs. We tested its effect on C. neoformans’ replicative lifespan (RLS). First, a mutant C. neoformans strain (sir2Δ) was generated, and confirmed a predicted shortened RLS in sir2Δ cells consistent with its known role in aging. Next, RLS analysis showed that treatment of C. neoformans with Sir2p-agonists resulted in a significantly prolonged RLS, whereas treatment with a Sir2p-antagonist shortened RLS. RLS modulating effects were dependent on SIR2 and not observed in sir2Δ cells. Because SIR2 loss resulted in a slightly impaired fitness, effects of genetic RLS modulation on virulence could not be compared with wild type cells. Instead we chose to chemically modulate RLS, and investigated the effect of Sir2p modulating drugs on C. neoformans cells in a Galleria mellonella infection model. Consistent with our hypothesis that shifts in the generational age of the infecting yeast population alters its vulnerability to host cells, we observed decreased virulence of C. neoformans in the Galleria host when RLS was prolonged by treatment with Sir2p agonists. In contrast, treatment with a Sir2p antagonist, which shortens RLS enhanced virulence in Galleria. In addition, combination of Sir2p agonists with antifungal therapy enhanced the antifungal’s effect. Importantly, no difference in virulence was observed with drug treatment when sir2Δ cells

  18. Basic and clinical pharmacology contribution to extend anthelmintic molecules lifespan.

    Science.gov (United States)

    Lanusse, Carlos; Lifschitz, Adrian; Alvarez, Luis

    2015-08-15

    The correct use of pharmacology-based information is critical to design successful strategies for the future of parasite control in livestock animals. Integrated pharmaco-parasitological research approaches have greatly contributed to optimize drug activity. In an attempt to manage drug resistance in helminths of ruminants, combinations of two or more anthelmintics are being used or promoted, based on the fact that individual worms may have a lower degree of resistance to a multiple component formulation, when each chemical has a different mode of action compared to that observed when a single compound is used. However, as emphasized in the current review, the occurrence of potential pharmacokinetic and/or pharmacodynamic interactions between drug components highlights the need for deeper and integrated research to identify the advantages or disadvantages associated with the use of combined drug preparations. This review article provides integrated pharmacokinetic/pharmacodynamic and clinical pharmacology information pertinent to preserve the traditional and modern active ingredients as practical tools for parasite control. Novel pharmacological data on derquantel and monepantel, as representatives of modern anthelmintics for use in livestock, is summarized here. The article also summarizes the pharmaco-parasitological knowledge considered critical to secure and/or extend the lifespan of the recently available novel molecules. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Developmental aspects of synaesthesia across the adult lifespan

    Directory of Open Access Journals (Sweden)

    Beat eMeier

    2014-03-01

    Full Text Available In synaesthesia, stimuli such as sounds, words or letters trigger experiences of colours, shapes or tastes and the consistency of these experiences is a hallmark of this condition. In this study we investigate for the first time whether there are age-related changes in the consistency of synaesthetic experiences. We tested a sample of more than 400 grapheme-colour synaesthetes who have colour experiences when they see letters and/or digits with a well-established test of consistency. Our results showed a decline in the number of consistent grapheme-colour associations across the adult lifespan. We also assessed age-related changes in the breadth of the colour spectrum. The results showed that the appearance of primary colours (i.e., red, blue, and green was mainly age-invariant. However, there was a decline in the occurrence of lurid colours while brown and achromatic tones occurred more often as concurrents in older age. These shifts in the colour spectrum suggest that synaesthesia does not simply fade, but rather undergoes more comprehensive changes. We propose that these changes are the result of a combination of both age-related perceptual and memory processing shifts.

  20. How long do centenarians survive? Life expectancy and maximum lifespan.

    Science.gov (United States)

    Modig, K; Andersson, T; Vaupel, J; Rau, R; Ahlbom, A

    2017-08-01

    The purpose of this study was to explore the pattern of mortality above the age of 100 years. In particular, we aimed to examine whether Scandinavian data support the theory that mortality reaches a plateau at particularly old ages. Whether the maximum length of life increases with time was also investigated. The analyses were based on individual level data on all Swedish and Danish centenarians born from 1870 to 1901; in total 3006 men and 10 963 women were included. Birth cohort-specific probabilities of dying were calculated. Exact ages were used for calculations of maximum length of life. Whether maximum age changed over time was analysed taking into account increases in cohort size. The results confirm that there has not been any improvement in mortality amongst centenarians in the past 30 years and that the current rise in life expectancy is driven by reductions in mortality below the age of 100 years. The death risks seem to reach a plateau of around 50% at the age 103 years for men and 107 years for women. Despite the rising life expectancy, the maximum age does not appear to increase, in particular after accounting for the increasing number of individuals of advanced age. Mortality amongst centenarians is not changing despite improvements at younger ages. An extension of the maximum lifespan and a sizeable extension of life expectancy both require reductions in mortality above the age of 100 years. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  1. The potential lifespan impact of gingivitis and periodontitis in children.

    Science.gov (United States)

    Bimstein, Enrique; Huja, Pinar Emecen; Ebersole, Jeffrey L

    2013-01-01

    The prevalence of gingivitis in children can be similar to or greater than dental caries, but has received much less attention in understanding the long-term impact on overall health. Oral health providers must take into consideration that the clinical presentation of the gingivitis progression/severity in the primary dentition is only evident when the magnitude of the inflammatory cell infiltrate approximates the gingival surface reflected by inflamed tissues. Moreover despite its relatively benign clinical appearance, the establishment of chronic inflammation of the periodontal tissues in childhood may have the potential for local tissue destruction leading to periodontitis, and/or create an "at-risk" environment in the tissues that could adversely affect the health of these tissues across the lifespan. The present manuscript presents some fundamental information regarding the characteristics of chronic inflammation in gingival tissues of children and adolescents and speculates about the lifetime impact of gingival and periodontal infections in childhood on future oral and systemic health in the adult.

  2. Lifespan theorem for simples constrained surface diffusion flows

    CERN Document Server

    Wheeler, Glen

    2012-01-01

    We consider closed immersed hypersurfaces in $\\R^3$ and $\\R^4$ evolving by a special class of constrained surface diffusion flows. This class of constrained flows includes the classical surface diffusion flow. In this paper we present a Lifespan Theorem for these flows, which gives a positive lower bound on the time for which a smooth solution exists, and a small upper bound on the total curvature during this time. The hypothesis of the theorem is that the surface is not already singular in terms of concentration of curvature. This turns out to be a deep property of the initial manifold, as the lower bound on maximal time obtained depends precisely upon the concentration of curvature of the initial manifold in $L^2$ for $M^2$ immersed in $R^3$ and additionally on the concentration in $L^3$ for $M^3$ immersed in $R^4$. This is stronger than a previous result on a different class of constrained surface diffusion flows, as here we obtain an improved lower bound on maximal time, a better estimate during this peri...

  3. Gambling on the lottery: sociodemographic correlates across the lifespan.

    Science.gov (United States)

    Barnes, Grace M; Welte, John W; Tidwell, Marie-Cecile O; Hoffman, Joseph H

    2011-12-01

    Two representative U.S. telephone surveys of gambling were conducted-an adult survey of adults aged 18 years and older (n = 2,631) and a youth survey of young people aged 14-21 years old (n = 2,274). Because the questions and methods were the same or similar in both surveys, the data from these two surveys were combined into a single dataset to examine the prevalence and sociodemographic correlates of gambling and problem gambling across the lifespan. The present work focused specifically on gambling on the lottery which is the most prevalent form of gambling in the U.S. The frequency of gambling on the lottery increased sharply from mid adolescence to age 18 which is the legal age to purchase lottery tickets in most states; lottery play continued to increase into the thirties when it leveled off and remained high through the sixties and then decreased among those 70 years and older. Considering multiple sociodemographic factors together in a negative binomial regression, the average number of days of lottery gambling was significantly predicted by male gender, age, neighborhood disadvantage and whether or not lottery was legal in the state where the respondent lived. These findings can be used to inform policies regarding lotteries in the U.S.

  4. Modeling Percentile Rank of Cardiorespiratory Fitness Across the Lifespan

    Science.gov (United States)

    Graves, Rasinio S.; Mahnken, Jonathan D.; Perea, Rodrigo D.; Billinger, Sandra A.; Vidoni, Eric D.

    2016-01-01

    Purpose The purpose of this investigation was to create an equation for continuous percentile rank of maximal oxygen consumption (VO2 max) from ages 20 to 99. Methods We used a two-staged modeling approach with existing normative data from the American College of Sports Medicine for VO2 max. First, we estimated intercept and slope parameters for each decade of life as a logistic function. We then modeled change in intercept and slope as functions of age (stage two) using weighted least squares regression. The resulting equations were used to predict fitness percentile rank based on age, sex, and VO2 max, and included estimates for individuals beyond 79 years old. Results We created a continuous, sex specific model of VO2 max percentile rank across the lifespan. Conclusions Percentile ranking of VO2 max can be made continuous and account for adults aged 20 to 99 with reasonable accuracy, improving the utility of this normalization procedure in practical and research settings, particularly in aging populations. PMID:26778922

  5. Sustained attention, attentional selectivity, and attentional capacity across the lifespan.

    Science.gov (United States)

    McAvinue, Laura P; Habekost, Thomas; Johnson, Katherine A; Kyllingsbæk, Søren; Vangkilde, Signe; Bundesen, Claus; Robertson, Ian H

    2012-11-01

    Changes in sustained attention, attentional selectivity, and attentional capacity were examined in a sample of 113 participants between the ages of 12 and 75. To measure sustained attention, we employed the sustained-attention-to-response task (Robertson, Manly, Andrade, Baddeley, & Yiend, Neuropsychologia 35:747-58, 1997), a short continuous-performance test designed to capture fluctuations in sustained attention. To measure attentional selectivity and capacity, we employed a paradigm based on the theory of visual attention (Bundesen, Psychological Review 97:523-547, 1990), which enabled the estimation of parameters related to attentional selection, perceptual threshold, visual short-term memory capacity, and processing capacity. We found evidence of age-related decline in each of the measured variables, but the declines varied markedly in terms of magnitude and lifespan trajectory. Variables relating to attentional capacity showed declines of very large effect sizes, while variables relating to attentional selectivity and sustained attention showed declines of medium to large effect sizes, suggesting that attentional control is relatively preserved in older adults. The variables relating to sustained attention followed a U-shaped, curvilinear trend, and the variables relating to attentional selectivity and capacity showed linear decline from early adulthood, providing further support for the differentiation of attentional functions.

  6. Neural Processing of Emotional Prosody across the Adult Lifespan

    Directory of Open Access Journals (Sweden)

    Liliana Ramona Demenescu

    2015-01-01

    Full Text Available Emotion recognition deficits emerge with the increasing age, in particular, a decline in the identification of sadness. However, little is known about the age-related changes of emotion processing in sensory, affective, and executive brain areas. This functional magnetic resonance imaging (fMRI study investigated neural correlates of auditory processing of prosody across adult lifespan. Unattended detection of emotional prosody changes was assessed in 21 young (age range: 18–35 years, 19 middle-aged (age range: 36–55 years, and 15 older (age range: 56–75 years adults. Pseudowords uttered with neutral prosody were standards in an oddball paradigm with angry, sad, happy, and gender deviants (total 20% deviants. Changes in emotional prosody and voice gender elicited bilateral superior temporal gyri (STG responses reflecting automatic encoding of prosody. At the right STG, responses to sad deviants decreased linearly with age, whereas happy events exhibited a nonlinear relationship. In contrast to behavioral data, no age by sex interaction emerged on the neural networks. The aging decline of emotion processing of prosodic cues emerges already at an early automatic stage of information processing at the level of the auditory cortex. However, top-down modulation may lead to an additional perceptional bias, for example, towards positive stimuli, and may depend on context factors such as the listener’s sex.

  7. Neural Processing of Emotional Prosody across the Adult Lifespan.

    Science.gov (United States)

    Demenescu, Liliana Ramona; Kato, Yutaka; Mathiak, Klaus

    2015-01-01

    Emotion recognition deficits emerge with the increasing age, in particular, a decline in the identification of sadness. However, little is known about the age-related changes of emotion processing in sensory, affective, and executive brain areas. This functional magnetic resonance imaging (fMRI) study investigated neural correlates of auditory processing of prosody across adult lifespan. Unattended detection of emotional prosody changes was assessed in 21 young (age range: 18-35 years), 19 middle-aged (age range: 36-55 years), and 15 older (age range: 56-75 years) adults. Pseudowords uttered with neutral prosody were standards in an oddball paradigm with angry, sad, happy, and gender deviants (total 20% deviants). Changes in emotional prosody and voice gender elicited bilateral superior temporal gyri (STG) responses reflecting automatic encoding of prosody. At the right STG, responses to sad deviants decreased linearly with age, whereas happy events exhibited a nonlinear relationship. In contrast to behavioral data, no age by sex interaction emerged on the neural networks. The aging decline of emotion processing of prosodic cues emerges already at an early automatic stage of information processing at the level of the auditory cortex. However, top-down modulation may lead to an additional perceptional bias, for example, towards positive stimuli, and may depend on context factors such as the listener's sex.

  8. Audiovisual Simultaneity Judgment and Rapid Recalibration throughout the Lifespan.

    Science.gov (United States)

    Noel, Jean-Paul; De Niear, Matthew; Van der Burg, Erik; Wallace, Mark T

    2016-01-01

    Multisensory interactions are well established to convey an array of perceptual and behavioral benefits. One of the key features of multisensory interactions is the temporal structure of the stimuli combined. In an effort to better characterize how temporal factors influence multisensory interactions across the lifespan, we examined audiovisual simultaneity judgment and the degree of rapid recalibration to paired audiovisual stimuli (Flash-Beep and Speech) in a sample of 220 participants ranging from 7 to 86 years of age. Results demonstrate a surprisingly protracted developmental time-course for both audiovisual simultaneity judgment and rapid recalibration, with neither reaching maturity until well into adolescence. Interestingly, correlational analyses revealed that audiovisual simultaneity judgments (i.e., the size of the audiovisual temporal window of simultaneity) and rapid recalibration significantly co-varied as a function of age. Together, our results represent the most complete description of age-related changes in audiovisual simultaneity judgments to date, as well as being the first to describe changes in the degree of rapid recalibration as a function of age. We propose that the developmental time-course of rapid recalibration scaffolds the maturation of more durable audiovisual temporal representations.

  9. Steroids as central regulators of organismal development and lifespan.

    Science.gov (United States)

    Lee, Siu Sylvia; Schroeder, Frank C

    2012-01-01

    Larvae of the nematode Caenorhabditis elegans must choose between reproductive development and dauer diapause. This decision is based on sensing of environmental inputs and dauer pheromone, a small molecule signal that serves to monitor population density. These signals are integrated via conserved neuroendocrine pathways that converge on steroidal ligands of the nuclear receptor DAF-12, a homolog of the mammalian vitamin D receptor and liver X receptor. DAF-12 acts as the main switch between gene expression programs that drive either reproductive development or dauer entry. Extensive studies in the past two decades demonstrated that biosynthesis of two bile acid-like DAF-12 ligands, named dafachronic acids (DA), controls developmental fate. In this issue of PLoS Biology, Wollam et al. showed that a conserved steroid-modifying enzyme, DHS-16, introduces a key feature in the structures of the DAF-12 ligands, closing a major gap in the DA biosynthesis pathway. The emerging picture of DA biosynthesis in C. elegans enables us to address a key question in the field: how are complex environmental signals integrated to enforce binary, organism-wide decisions on developmental fate? Schaedel et al. demonstrated that pheromone and DA serve as competing signals, and that a positive feedback loop based on regulation of DA biosynthesis ensures organism-wide commitment to reproductive development. Considering that many components of DA signaling are highly conserved, ongoing studies in C. elegans may reveal new aspects of bile acid function and lifespan regulation in mammals.

  10. Audiovisual Simultaneity Judgment and Rapid Recalibration throughout the Lifespan

    Science.gov (United States)

    De Niear, Matthew; Van der Burg, Erik; Wallace, Mark T.

    2016-01-01

    Multisensory interactions are well established to convey an array of perceptual and behavioral benefits. One of the key features of multisensory interactions is the temporal structure of the stimuli combined. In an effort to better characterize how temporal factors influence multisensory interactions across the lifespan, we examined audiovisual simultaneity judgment and the degree of rapid recalibration to paired audiovisual stimuli (Flash-Beep and Speech) in a sample of 220 participants ranging from 7 to 86 years of age. Results demonstrate a surprisingly protracted developmental time-course for both audiovisual simultaneity judgment and rapid recalibration, with neither reaching maturity until well into adolescence. Interestingly, correlational analyses revealed that audiovisual simultaneity judgments (i.e., the size of the audiovisual temporal window of simultaneity) and rapid recalibration significantly co-varied as a function of age. Together, our results represent the most complete description of age-related changes in audiovisual simultaneity judgments to date, as well as being the first to describe changes in the degree of rapid recalibration as a function of age. We propose that the developmental time-course of rapid recalibration scaffolds the maturation of more durable audiovisual temporal representations. PMID:27551918

  11. Metformin Alleviates Aging Cellular Phenotypes in Hutchinson-Gilford Progeria Syndrome Dermal Fibroblasts.

    Science.gov (United States)

    Park, Seul-Ki; Shin, Ok Sarah

    2017-02-13

    Metformin is a popular antidiabetic biguanide, which has been considered as a candidate drug for cancer treatment and aging prevention. Hutchinson-Gilford progeria syndrome (HGPS) is a devastating disease characterized by premature aging and severe age-associated complications leading to death. The effects of metformin on HGPS dermal fibroblasts remain largely undefined. In this study, we investigated whether metformin could exert a beneficial effect on nuclear abnormalities and delay senescence in fibroblasts derived from HGPS patients. Metformin treatment partially restored normal nuclear phenotypes, delayed senescence, activated the phosphorylation of AMP-activated protein kinase, and decreased reactive oxygen species formation in HGPS dermal fibroblasts. Interestingly, metformin reduced the number of phosphorylated histone variant H2AX-positive DNA damage foci and suppressed progerin protein expression, compared to the control. Furthermore, metformin-supplemented aged mice showed higher splenocyte proliferation and mRNA expression of the antioxidant enzyme, superoxide dismutase 2 than the control mice. Collectively, our results show that metformin treatment alleviates the nuclear defects and premature aging phenotypes in HGPS fibroblasts. Thus, metformin can be considered a promising therapeutic approach for life extension in HGPS. This article is protected by copyright. All rights reserved.

  12. Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan

    OpenAIRE

    Liu, Zhi-Jian; Hoffmeister, Karin M.; Hu, Zhongbo; Mager, Donald E.; Ait-Oudhia, Sihem; Debrincat, Marlyse A.; Pleines, Irina; Josefsson, Emma C.; Benjamin T Kile; Italiano, Joseph; Ramsey, Haley; Grozovsky, Renata; Veng-Pedersen, Peter; Chavda, Chaitanya; Sola-Visner, Martha

    2014-01-01

    Rapid growth and rising platelet counts result in a significant expansion of platelet mass during neonatal life.The rise in platelet counts is mediated by a prolongation in the neonatal platelet lifespan.

  13. Post engineered nanomaterials lifespan: nanowastes classification, legislative development/implementation challenges, and proactive approaches

    CSIR Research Space (South Africa)

    Musee, N

    2012-05-01

    Full Text Available -1 NANOLCA Symposium, "Safety issues and regulatory challenges of nanomaterials", San Sebastian, Spain, 3-4 May 2012 Post engineered nanomaterials lifespan: nanowastes classification, legislative development/implementation challenges, and proactive...

  14. Building Lifespan: Effect on the Environmental Impact of Building Components in a Danish Perspective

    DEFF Research Database (Denmark)

    Marsh, Rob

    2016-01-01

    Construction professionals must now integrate environmental concerns with life cycle assessment (LCA) early in the procurement process. Building lifespan is important to LCA, since results must be normalized on an annualized basis for comparison. However, the scientific literature shows that issues...... of building lifespan are inadequately addressed. The aim of this research is therefore to explore how environmental impact from building components is affected by building lifespans of 50, 80, 100 and 120 years in a Danish context. LCAs are undertaken for 792 parametric variations of typical construction...... solutions, covering all primary building components and based on contemporary practice. A full statistical analysis is carried out, which shows a significant statistical correlation between changes in building lifespan and environmental impact for all primary building components, except windows...

  15. Nmdmc overexpression extends Drosophila lifespan and reduces levels of mitochondrial reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Suyeun [Department of Preventive Medicine, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Jang, Yeogil; Paik, Donggi [Department of Physiology, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Lee, Eunil, E-mail: eunil@korea.ac.kr [Department of Preventive Medicine, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Park, Joong-Jean, E-mail: parkjj@korea.ac.kr [Department of Physiology, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of)

    2015-10-02

    NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase (NMDMC) is a bifunctional enzyme involved in folate-dependent metabolism and highly expressed in rapidly proliferating cells. However, Nmdmc physiological roles remain unveiled. We found that ubiquitous Nmdmc overexpression enhanced Drosophila lifespan and stress resistance. Interestingly, Nmdmc overexpression in the fat body was sufficient to increase lifespan and tolerance against oxidative stress. In addition, these conditions coincided with significant decreases in the levels of mitochondrial ROS and Hsp22 as well as with a significant increase in the copy number of mitochondrial DNA. These results suggest that Nmdmc overexpression should be beneficial for mitochondrial homeostasis and increasing lifespan. - Highlights: • Ubiquitous Nmdmc overexpression enhanced lifespan and stress tolerance. • Nmdmc overexpression in the fat body extended longevity. • Fat body-specific Nmdmc overexpression increased oxidative stress resistance. • Nmdmc overexpression decreased Hsp22 transcript levels and ROS. • Nmdmc overexpression increased mitochondrial DNA copy number.

  16. Lifespan differences in hematopoietic stem cells are due to imperfect repair and unstable mean-reversion.

    Directory of Open Access Journals (Sweden)

    Hans B Sieburg

    2013-04-01

    Full Text Available The life-long supply of blood cells depends on the long-term function of hematopoietic stem cells (HSCs. HSCs are functionally defined by their multi-potency and self-renewal capacity. Because of their self-renewal capacity, HSCs were thought to have indefinite lifespans. However, there is increasing evidence that genetically identical HSCs differ in lifespan and that the lifespan of a HSC is predetermined and HSC-intrinsic. Lifespan is here defined as the time a HSC gives rise to all mature blood cells. This raises the intriguing question: what controls the lifespan of HSCs within the same animal, exposed to the same environment? We present here a new model based on reliability theory to account for the diversity of lifespans of HSCs. Using clonal repopulation experiments and computational-mathematical modeling, we tested how small-scale, molecular level, failures are dissipated at the HSC population level. We found that the best fit of the experimental data is provided by a model, where the repopulation failure kinetics of each HSC are largely anti-persistent, or mean-reverting, processes. Thus, failure rates repeatedly increase during population-wide division events and are counteracted and decreased by repair processes. In the long-run, a crossover from anti-persistent to persistent behavior occurs. The cross-over is due to a slow increase in the mean failure rate of self-renewal and leads to rapid clonal extinction. This suggests that the repair capacity of HSCs is self-limiting. Furthermore, we show that the lifespan of each HSC depends on the amplitudes and frequencies of fluctuations in the failure rate kinetics. Shorter and longer lived HSCs differ significantly in their pre-programmed ability to dissipate perturbations. A likely interpretation of these findings is that the lifespan of HSCs is determined by preprogrammed differences in repair capacity.

  17. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jeremy M Van Raamsdonk

    2009-02-01

    Full Text Available The oxidative stress theory of aging postulates that aging results from the accumulation of molecular damage caused by reactive oxygen species (ROS generated during normal metabolism. Superoxide dismutases (SODs counteract this process by detoxifying superoxide. It has previously been shown that elimination of either cytoplasmic or mitochondrial SOD in yeast, flies, and mice results in decreased lifespan. In this experiment, we examine the effect of eliminating each of the five individual sod genes present in Caenorhabditis elegans. In contrast to what is observed in other model organisms, none of the sod deletion mutants shows decreased lifespan compared to wild-type worms, despite a clear increase in sensitivity to paraquat- and juglone-induced oxidative stress. In fact, even mutants lacking combinations of two or three sod genes survive at least as long as wild-type worms. Examination of gene expression in these mutants reveals mild compensatory up-regulation of other sod genes. Interestingly, we find that sod-2 mutants are long-lived despite a significant increase in oxidatively damaged proteins. Testing the effect of sod-2 deletion on known pathways of lifespan extension reveals a clear interaction with genes that affect mitochondrial function: sod-2 deletion markedly increases lifespan in clk-1 worms while clearly decreasing the lifespan of isp-1 worms. Combined with the mitochondrial localization of SOD-2 and the fact that sod-2 mutant worms exhibit phenotypes that are characteristic of long-lived mitochondrial mutants-including slow development, low brood size, and slow defecation-this suggests that deletion of sod-2 extends lifespan through a similar mechanism. This conclusion is supported by our demonstration of decreased oxygen consumption in sod-2 mutant worms. Overall, we show that increased oxidative stress caused by deletion of sod genes does not result in decreased lifespan in C. elegans and that deletion of sod-2 extends worm

  18. Lifespan and reproduction of isoclonal individual E.coli in different environments

    DEFF Research Database (Denmark)

    Jouvet, Lionel; Steiner, Ulrich

    Lifespan and reproduction are key fitness components, both of which are influences by genetics and the environment. Tracking large numbers of genotypically known individuals throughout their lives in known environments has been challenging. Here we show for isogenic individual E. coli bacteria...... under controlled environments how demographic parameters and distributions in reproduction and survival change across environments. We achieve this by using a microfluidic device that traps thousands of individual E. coli cells and tracks their division (reproduction) over their lifespan. Our results...

  19. Lifespan, growth rate, and body size across latitude in marine Bivalvia, with implications for Phanerozoic evolution.

    Science.gov (United States)

    Moss, David K; Ivany, Linda C; Judd, Emily J; Cummings, Patrick W; Bearden, Claire E; Kim, Woo-Jun; Artruc, Emily G; Driscoll, Jeremy R

    2016-08-17

    Mean body size in marine animals has increased more than 100-fold since the Cambrian, a discovery that brings to attention the key life-history parameters of lifespan and growth rate that ultimately determine size. Variation in these parameters is not well understood on the planet today, much less in deep time. Here, we present a new global database of maximum reported lifespan and shell growth coupled with body size data for 1 148 populations of marine bivalves and show that (i) lifespan increases, and growth rate decreases, with latitude, both across the group as a whole and within well-sampled species, (ii) growth rate, and hence metabolic rate, correlates inversely with lifespan, and (iii) opposing trends in lifespan and growth combined with high variance obviate any demonstrable pattern in body size with latitude. Our observations suggest that the proposed increase in metabolic activity and demonstrated increase in body size of organisms over the Phanerozoic should be accompanied by a concomitant shift towards faster growth and/or shorter lifespan in marine bivalves. This prediction, testable from the fossil record, may help to explain one of the more fundamental patterns in the evolutionary and ecological history of animal life on this planet.

  20. Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans

    Science.gov (United States)

    Kumar, Jitendra; Barhydt, Tracy; Awasthi, Anjali; Lithgow, Gordon J.; Killilea, David W.; Kapahi, Pankaj

    2016-01-01

    Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy. PMID:27078872

  1. Green tea polyphenols extend the lifespan of male drosophila melanogaster while impairing reproductive fitness.

    Science.gov (United States)

    Lopez, Terry; Schriner, Samuel E; Okoro, Michael; Lu, David; Chiang, Beatrice T; Huey, Jocelyn; Jafari, Mahtab

    2014-12-01

    Green tea is a popular beverage believed to have many health benefits, including a reduction in the risks of heart disease and cancer. Rich in polyphenolic compounds known as catechins, green tea and its components have been shown to increase the lifespan of various animal models, including Drosophila melanogaster. Here, we investigated the gender-specific effects of green tea on the lifespan of fruit flies and observed that green tea extended the lifespan of male flies only. This effect was found to be independent of typical aging interventions, such as dietary restriction, modulation of oxidative energy metabolism, and improved tolerance to environmental stresses. The one exception was that green tea did protect male flies against iron toxicity. Since there is an inverse correlation between lifespan and reproduction, the impact of green tea on male reproductive fitness was also investigated. We found that green tea negatively impacted male fertility as shown by a reduced number of offspring produced and increased mating latency. We further identified that the lifespan extension properties of green tea was only observed in the presence of females which alludes to a reproductive (or mating) dependent mechanism. Our findings suggest that green tea extends the lifespan of male flies by inhibiting reproductive potential, possibly by limiting iron uptake. To our knowledge, our study is the first to report the negative impact of green tea on Drosophila male reproduction. Our results also support previous studies that suggest that green tea might have a negative effect on reproductive fitness in humans.

  2. Reduced lifespan and increased ageing driven by genetic drift in small populations.

    Science.gov (United States)

    Lohr, Jennifer N; David, Patrice; Haag, Christoph R

    2014-09-01

    Explaining the strong variation in lifespan among organisms remains a major challenge in evolutionary biology. Whereas previous work has concentrated mainly on differences in selection regimes and selection pressures, we hypothesize that differences in genetic drift may explain some of this variation. We develop a model to formalize this idea and show that the strong positive relationship between lifespan and genetic diversity predicted by this model indeed exists among populations of Daphnia magna, and that ageing is accelerated in small populations. Additional results suggest that this is due to increased drift in small populations rather than adaptation to environments favoring faster life histories. First, the correlation between genetic diversity and lifespan remains significant after statistical correction for potential environmental covariates. Second, no trade-offs are observed; rather, all investigated traits show clear signs of increased genetic load in the small populations. Third, hybrid vigor with respect to lifespan is observed in crosses between small but not between large populations. Together, these results suggest that the evolution of lifespan and ageing can be strongly affected by genetic drift, especially in small populations, and that variation in lifespan and ageing may often be nonadaptive, due to a strong contribution from mutation accumulation.

  3. Sexes suffer from suboptimal lifespan because of genetic conflict in a seed beetle.

    Science.gov (United States)

    Berg, Elena C; Maklakov, Alexei A

    2012-10-22

    Males and females have different routes to successful reproduction, resulting in sex differences in lifespan and age-specific allocation of reproductive effort. The trade-off between current and future reproduction is often resolved differently by males and females, and both sexes can be constrained in their ability to reach their sex-specific optima owing to intralocus sexual conflict. Such genetic antagonism may have profound implications for evolution, but its role in ageing and lifespan remains unresolved. We provide direct experimental evidence that males live longer and females live shorter than necessary to maximize their relative fitness in Callosobruchus maculatus seed beetles. Using artificial selection in a genetically heterogeneous population, we created replicate long-life lines where males lived on average 27 per cent longer than in short-life lines. As predicted by theory, subsequent assays revealed that upward selection on male lifespan decreased relative male fitness but increased relative female fitness compared with downward selection. Thus, we demonstrate that lifespan-extending genes can help one sex while harming the other. Our results show that sexual antagonism constrains adaptive life-history evolution, support a novel way of maintaining genetic variation for lifespan and argue for better integration of sex effects into applied research programmes aimed at lifespan extension.

  4. Dairy Propionibacterium extends the mean lifespan of Caenorhabditis elegans via activation of the innate immune system.

    Science.gov (United States)

    Kwon, Gayeung; Lee, Jiyun; Lim, Young-Hee

    2016-08-17

    Dairy Propionibacterium freudenreichii is a candidate non-lactic acid probiotic. However, little information is available on the effect of P. freudenreichii on lifespan extension in humans. The aim of this study was to evaluate the effects of P. freudenreichii on lifespan extension and to elucidate the mechanism of P. freudenreichii-dependent lifespan extension in Caenorhabditis elegans. The results showed that P. freudenreichii significantly (p OP50, a standard food for the worm. Analysis of age-related biomarkers showed that P. freudenreichii retards ageing. Moreover, P. freudenreichii increased resistance against a human pathogen, Salmonella typhimurium, through the activation of skn-1, which is involved in pathogen resistance in C. elegans. Furthermore, P. freudenreichii-fed daf-16, jnk-1, skn-1 or daf-7 loss-of-function mutants showed an extended mean lifespan compared with E. coli OP50-fed worms. However, the increase in lifespan was not observed in pmk-1, sek-1, mek-1, dbl-1, daf-12 or daf-2 mutants, which suggests potential roles for these genes in P. freudenreichii-induced longevity in C. elegans. In conclusion, P. freudenreichii extends the lifespan of C. elegans via the p38 MAPK pathway involved in stress response and the TGF-β pathways associated with anti-inflammation processes in the immune system.

  5. Lipid-lowering fibrates extend C. elegans lifespan in a NHR-49/PPARalpha-dependent manner.

    Science.gov (United States)

    Brandstädt, Sven; Schmeisser, Kathrin; Zarse, Kim; Ristow, Michael

    2013-04-01

    Compounds that delay aging in model organisms may be of significant interest to anti-aging medicine, since these substances potentially provide pharmaceutical approaches to promote healthy lifespan in humans. We here aimed to test whether pharmaceutical concentrations of three fibrates, pharmacologically established serum lipid-lowering drugs and ligands of the nuclear receptor PPARalpha in mammals, are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Adult C. elegans (wild-type N2 as well as two nhr-49-deficient strains, RB1716 and VC870) were maintained on agar plates and were fed E. coli strain OP50 bacteria. Bezafibrate, clofibrate, and fenofibrate were applied to the agar, respectively, to test whether they may promote longevity by quantifying survival in the presence and absence of the respective compounds. All three fibrates extended C. elegans N2 lifespan when applied at a concentration of 10 micromolar. Bezafibrate additionally extended C. elegans N2 lifespan at concentrations of 1 micromolar and 0.1 micromolar. In strains deficient for nhr-49, a functional orthologue of the mammalian peroxisome proliferator-activated receptor alpha (PPARalpha), all three compounds were incapable of extending lifespan. Taken together, fibrates promote C. elegans longevity in an NHR-49-dependent manner possibly by promoting mitohormesis and suggesting that these compounds may promote lifespan also in mammals.

  6. The lifespan-extending effects of Nymphaea hybrid root extract in the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Zhuang, Ziheng; Lv, Ting; Li, Min; Zhang, Yusi; Xue, Ting; Yang, Linsong; Liu, Hui; Zhang, Weiming

    2014-12-01

    Nymphaea hybrid, a water lily from the Nymphaeaceae family, has been found to exhibit some in vivo beneficial effects. In the present study we investigated the lifespan-extending effects of Nymphaea hybrid root extract in the nematode Caenorhabditis elegans. We found that Nymphaea hybrid root extract significantly extended the lifespan of C.elegans and improved its locomotion during aging. Moreover, Nymphaea hybrid root extract increased the resistance of C.elegans to both heat stress and oxidative stress. We found that the ability of Nymphaea hybrid root extract to increase lifespan was independent of its antimicrobial effects and was probably associated with its effects on the reproduction of C.elegans. In addition, the lifespan-extending effects of Nymphaea hybrid root extract were found to be dependent on the insulin/IGF signaling pathway. We also found that total flavones of Nymphaea hybrid could increase survival of C.elegans in both normal and adverse conditions, indicating that total flavones comprise the major fractions with lifespan-extending effects. Therefore, Nymphaea hybrid root extract has lifespan-extending effects in C.elegans and could be developed as a functional food.

  7. Royalactin extends lifespan of Caenorhabditis elegans through epidermal growth factor signaling.

    Science.gov (United States)

    Detienne, Giel; De Haes, Wouter; Ernst, Ulrich R; Schoofs, Liliane; Temmerman, Liesbet

    2014-12-01

    Royalactin is a glycoprotein essential for the development of long-lived queen honeybees. Only larvae fed with royal jelly, containing royalactin, develop into queens. Royalactin plays a central role in this process by switching on the epidermal growth factor (EGF) receptor signaling pathway which ultimately leads to epigenetic changes and a long-lived queen phenotype. Recently it was shown that royalactin by itself also extends lifespan in Drosophila melanogaster. Yet, the mechanism by which royalactin promotes longevity remains largely unknown. We set out to characterize the effects of royalactin on Caenorhabditis elegans lifespan, and clarify the possible involvement of EGF signaling in this process. We demonstrate that royalactin extends lifespan of this nematode and that both EGF (LIN-3) and its receptor (LET-23) are essential to this process. To our knowledge, this is the first report of royalactin-mediated lifespan extension in a non-insect species. Additionally, we show that royalactin enhances locomotion in adult nematodes, implying that royalactin also influences healthspan. Our results suggest that royalactin is an important lifespan-extending factor in royal jelly and acts by promoting EGF signaling in C. elegans. Further work will now be needed to clarify which (secondary) signaling pathways are activated by royalactin, and how this ultimately translates into an extended health- and lifespan.

  8. Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans.

    Science.gov (United States)

    Kumar, Jitendra; Barhydt, Tracy; Awasthi, Anjali; Lithgow, Gordon J; Killilea, David W; Kapahi, Pankaj

    2016-01-01

    Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy.

  9. Flat Cellular (UMTS) Networks

    NARCIS (Netherlands)

    Bosch, H.G.P.; Samuel, L.G.; Mullender, S.J.; Polakos, P.; Rittenhouse, G.

    2007-01-01

    Traditionally, cellular systems have been built in a hierarchical manner: many specialized cellular access network elements that collectively form a hierarchical cellular system. When 2G and later 3G systems were designed there was a good reason to make system hierarchical: from a cost-perspective i

  10. Effects of rapamycin induced cellular autophagy in aging-related diseases%雷帕霉素诱导细胞自噬在衰老相关疾病中的作用

    Institute of Scientific and Technical Information of China (English)

    吴伯艳; 刘新光; 陈维春

    2015-01-01

    哺乳动物雷帕霉素靶蛋白( mammalian target of rapamy-cin, mTOR)是衰老和衰老相关疾病的一个关键调节因子。雷帕霉素( rapamycin, RAPA)可通过抑制mTOR通路,诱导和促进细胞自噬的发生。细胞自噬是维持细胞内稳态的主要方式与途径,通过降解多余的、受损的及衰老的蛋白与细胞器,为细胞重建、再生和修复提供必需原料。早老症( hutchinson-gil-ford progeria syndrome, HGPS )患者细胞中伴随早老蛋白( progerin)的异常聚集;此外,诸如亨廷顿病、帕金森病、阿尔茨海默病等神经退行性疾病细胞内同样出现异常蛋白质的聚集,而这些异常蛋白的清除正依赖于细胞的自噬作用。由此可见,雷帕霉素是潜在的抗衰老、治疗早老症及衰老相关疾病的重要药物。该文主要阐述雷帕霉素促进细胞自噬方面的功能及在HGPS、神经退行性疾病方面的应用。%Mammalian target of rapamycin( mTOR) is a key reg-ulator of aging and aging-related diseases. Rapamycin ( RAPA) induces and promotes the process of cell autophagy through in-hibiting mTOR pathway. Autophagy exerts a crucial role in main-taining the cellular meostasis, which provides essential materials for cell reconstruction, regeneration and repair via degradating the redundant, damaged, or senescent proteins and organelles. Hutchinson Gilford progeria syndrome ( HGPS ) patients are al-ways accompanied with abnormally accumulated progerin in cells. Similar to HGPS, abnormal protein accumulation is the common pathological feature of neurodegenerative diseases, in-cluding Huntington′s disease, Parkinson′s disease, Alzheimer′s disease and so on. Degradation of these abnormal proteins pre-dominantly depends on cell autophagy. Thus, rapamycin is a po-tential anti-aging drug for HGPS and aging-related diseases thera-py. This view focuses on the effects of rapamycin on cell autoph-agy and clinical application in HGPS and neurodegenerative

  11. Lifespan anxiety is reflected in human amygdala cortical connectivity.

    Science.gov (United States)

    He, Ye; Xu, Ting; Zhang, Wei; Zuo, Xi-Nian

    2016-03-01

    The amygdala plays a pivotal role in processing anxiety and connects to large-scale brain networks. However, intrinsic functional connectivity (iFC) between amygdala and these networks has rarely been examined in relation to anxiety, especially across the lifespan. We employed resting-state functional MRI data from 280 healthy adults (18-83.5 yrs) to elucidate the relationship between anxiety and amygdala iFC with common cortical networks including the visual network, somatomotor network, dorsal attention network, ventral attention network, limbic network, frontoparietal network, and default network. Global and network-specific iFC were separately computed as mean iFC of amygdala with the entire cerebral cortex and each cortical network. We detected negative correlation between global positive amygdala iFC and trait anxiety. Network-specific associations between amygdala iFC and anxiety were also detectable. Specifically, the higher iFC strength between the left amygdala and the limbic network predicted lower state anxiety. For the trait anxiety, left amygdala anxiety-connectivity correlation was observed in both somatomotor and dorsal attention networks, whereas the right amygdala anxiety-connectivity correlation was primarily distributed in the frontoparietal and ventral attention networks. Ventral attention network exhibited significant anxiety-gender interactions on its iFC with amygdala. Together with findings from additional vertex-wise analysis, these data clearly indicated that both low-level sensory networks and high-level associative networks could contribute to detectable predictions of anxiety behaviors by their iFC profiles with the amygdala. This set of systems neuroscience findings could lead to novel functional network models on neural correlates of human anxiety and provide targets for novel treatment strategies on anxiety disorders.

  12. Lifespan anxiety is reflected in human amygdala cortical connectivity

    Science.gov (United States)

    He, Ye; Xu, Ting; Zhang, Wei

    2016-01-01

    Abstract The amygdala plays a pivotal role in processing anxiety and connects to large‐scale brain networks. However, intrinsic functional connectivity (iFC) between amygdala and these networks has rarely been examined in relation to anxiety, especially across the lifespan. We employed resting‐state functional MRI data from 280 healthy adults (18–83.5 yrs) to elucidate the relationship between anxiety and amygdala iFC with common cortical networks including the visual network, somatomotor network, dorsal attention network, ventral attention network, limbic network, frontoparietal network, and default network. Global and network‐specific iFC were separately computed as mean iFC of amygdala with the entire cerebral cortex and each cortical network. We detected negative correlation between global positive amygdala iFC and trait anxiety. Network‐specific associations between amygdala iFC and anxiety were also detectable. Specifically, the higher iFC strength between the left amygdala and the limbic network predicted lower state anxiety. For the trait anxiety, left amygdala anxiety–connectivity correlation was observed in both somatomotor and dorsal attention networks, whereas the right amygdala anxiety–connectivity correlation was primarily distributed in the frontoparietal and ventral attention networks. Ventral attention network exhibited significant anxiety–gender interactions on its iFC with amygdala. Together with findings from additional vertex‐wise analysis, these data clearly indicated that both low‐level sensory networks and high‐level associative networks could contribute to detectable predictions of anxiety behaviors by their iFC profiles with the amygdala. This set of systems neuroscience findings could lead to novel functional network models on neural correlates of human anxiety and provide targets for novel treatment strategies on anxiety disorders. Hum Brain Mapp 37:1178–1193, 2016. © 2015 The Authors Human Brain Mapping

  13. Epigenetic programming by stress and glucocorticoids along the human lifespan.

    Science.gov (United States)

    Zannas, A S; Chrousos, G P

    2017-03-14

    Psychosocial stress triggers a set of behavioral, neural, hormonal, and molecular responses that can be a driving force for survival when adaptive and time-limited, but may also contribute to a host of disease states if dysregulated or chronic. The beneficial or detrimental effects of stress are largely mediated by the hypothalamic-pituitary axis, a highly conserved neurohormonal cascade that culminates in systemic secretion of glucocorticoids. Glucocorticoids activate the glucocorticoid receptor, a ubiquitous nuclear receptor that not only causes widespread changes in transcriptional programs, but also induces lasting epigenetic modifications in many target tissues. While the epigenome remains sensitive to stressors throughout life, we propose two key principles that may govern the epigenetics of stress and glucocorticoids along the lifespan: first, the presence of distinct life periods, during which the epigenome shows heightened plasticity to stress exposure, such as in early development and at advanced age; and, second, the potential of stress-induced epigenetic changes to accumulate throughout life both in select chromatin regions and at the genome-wide level. These principles have important clinical and translational implications, and they show striking parallels with the existence of sensitive developmental periods and the cumulative impact of stressful experiences on the development of stress-related phenotypes. We hope that this conceptual mechanistic framework will stimulate fruitful research that aims at unraveling the molecular pathways through which our life stories sculpt genomic function to contribute to complex behavioral and somatic phenotypes.Molecular Psychiatry advance online publication, 14 March 2017; doi:10.1038/mp.2017.35.

  14. Joint inhibition of TOR and JNK pathways interacts to extend the lifespan of Brachionus manjavacas (Rotifera).

    Science.gov (United States)

    Snell, Terry W; Johnston, Rachel K; Rabeneck, Brett; Zipperer, Cody; Teat, Stephanie

    2014-04-01

    The TOR kinase pathway is central in modulating aging in a variety of animal models. The target of rapamycin (TOR) integrates a complex network of signals from growth conditions, nutrient availability, energy status, and physiological stresses and matches an organism's growth rate to the resource environment. Important remaining problems are the identification of the pathways that interact with TOR and their characterization as additive or synergistic. One of the most versatile stress sensors in metazoans is the Jun-N-terminal kinase (JNK) signaling pathway. JNK is an evolutionarily conserved stress-activated protein kinase that is induced by a range of stressors, including UV irradiation, reactive oxygen species, DNA damage, heat, and bacterial antigens. JNK is thought to interact with the TOR pathway, but its effects on TOR are poorly understood. We used the rotifer Brachionus manjavacas as a model animal to probe the regulation of TOR and JNK pathways and explore their interaction. The effect of various chemical inhibitors was examined in life table and stressor challenge experiments. A survey of 12 inhibitors revealed two, rapamycin and JNK inhibitor, that significantly extended lifespan of B. manjavacas. At 1 μM concentration, exposure to rapamycin or JNK inhibitor extended mean rotifer lifespan by 35% and maximum lifespan by 37%. Exposure to both rapamycin and JNK inhibitor simultaneously extended mean rotifer lifespan by 65% more than either alone. Exposure to a combination of rapamycin and JNK inhibitors conveyed greater protection to starvation, UV and osmotic stress than either inhibitor alone. RNAi knockdown of TOR and JNK gene expression was investigated for its ability to extend rotifer lifespan. RNAi knockdown of the TOR gene resulted in 29% extension of the mean lifespan compared to control and knockdown of the JNK gene resulted in 51% mean lifespan extension. In addition to the lifespan, we quantified mitochondria activity using the fluorescent

  15. GABA metabolism pathway genes, UGA1 and GAD1, regulate replicative lifespan in Saccharomycescerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Kamei, Yuka; Tamura, Takayuki [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan); Yoshida, Ryo [Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ohta, Shinji [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan); Fukusaki, Eiichiro [Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Mukai, Yukio, E-mail: y_mukai@nagahama-i-bio.ac.jp [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan)

    2011-04-01

    Highlights: {yields}We demonstrate that two genes in the yeast GABA metabolism pathway affect aging. {yields} Deletion of the UGA1 or GAD1 genes extends replicative lifespan. {yields} Addition of GABA to wild-type cultures has no effect on lifespan. {yields} Intracellular GABA levels do not differ in longevity mutants and wild-type cells. {yields} Levels of tricarboxylic acid cycle intermediates positively correlate with lifespan. -- Abstract: Many of the genes involved in aging have been identified in organisms ranging from yeast to human. Our previous study showed that deletion of the UGA3 gene-which encodes a zinc-finger transcription factor necessary for {gamma}-aminobutyric acid (GABA)-dependent induction of the UGA1 (GABA aminotransferase), UGA2 (succinate semialdehyde dehydrogenase), and UGA4 (GABA permease) genes-extends replicative lifespan in the budding yeast Saccharomycescerevisiae. Here, we found that deletion of UGA1 lengthened the lifespan, as did deletion of UGA3; in contrast, strains with UGA2 or UGA4 deletions exhibited no lifespan extension. The {Delta}uga1 strain cannot deaminate GABA to succinate semialdehyde. Deletion of GAD1, which encodes the glutamate decarboxylase that converts glutamate into GABA, also increased lifespan. Therefore, two genes in the GABA metabolism pathway, UGA1 and GAD1, were identified as aging genes. Unexpectedly, intracellular GABA levels in mutant cells (except for {Delta}uga2 cells) did not differ from those in wild-type cells. Addition of GABA to culture media, which induces transcription of the UGA structural genes, had no effect on replicative lifespan of wild-type cells. Multivariate analysis of {sup 1}H nuclear magnetic resonance spectra for the whole-cell metabolite levels demonstrated a separation between long-lived and normal-lived strains. Gas chromatography-mass spectrometry analysis of identified metabolites showed that levels of tricarboxylic acid cycle intermediates positively correlated with lifespan

  16. Reevaluation of whether a soma–to–germ-line transformation extends lifespan in Caenorhabditis elegans

    Science.gov (United States)

    Knutson, Andrew Kekūpa'a; Rechtsteiner, Andreas; Strome, Susan

    2016-01-01

    The germ lineage is considered to be immortal. In the quest to extend lifespan, a possible strategy is to drive germ-line traits in somatic cells, to try to confer some of the germ lineage’s immortality on the somatic body. Notably, a study in Caenorhabditis elegans suggested that expression of germ-line genes in the somatic cells of long-lived daf-2 mutants confers some of daf-2’s long lifespan. Specifically, mRNAs encoding components of C. elegans germ granules (P granules) were up-regulated in daf-2 mutant worms, and knockdown of individual P-granule and other germ-line genes in daf-2 young adults modestly reduced their lifespan. We investigated the contribution of a germ-line program to daf-2’s long lifespan and also tested whether other mutants known to express germ-line genes in their somatic cells are long-lived. Our key findings are as follows. (i) We could not detect P-granule proteins in the somatic cells of daf-2 mutants by immunostaining or by expression of a P-granule transgene. (ii) Whole-genome transcript profiling of animals lacking a germ line revealed that germ-line transcripts are not up-regulated in the soma of daf-2 worms compared with the soma of control worms. (iii) Simultaneous removal of multiple P-granule proteins or the entire germ-line program from daf-2 worms did not reduce their lifespan. (iv) Several mutants that robustly express a broad spectrum of germ-line genes in their somatic cells are not long-lived. Together, our findings argue against the hypothesis that acquisition of a germ-cell program in somatic cells increases lifespan and contributes to daf-2’s long lifespan. PMID:26976573

  17. Acidic Food pH Increases Palatability and Consumption and Extends Drosophila Lifespan.

    Science.gov (United States)

    Deshpande, Sonali A; Yamada, Ryuichi; Mak, Christine M; Hunter, Brooke; Soto Obando, Alina; Hoxha, Sany; Ja, William W

    2015-12-01

    Despite the prevalent use of Drosophila as a model in studies of nutrition, the effects of fundamental food properties, such as pH, on animal health and behavior are not well known. We examined the effect of food pH on adult Drosophila lifespan, feeding behavior, and microbiota composition and tested the hypothesis that pH-mediated changes in palatability and total consumption are required for modulating longevity. We measured the effect of buffered food (pH 5, 7, or 9) on male gustatory responses (proboscis extension), total food intake, and male and female lifespan. The effect of food pH on germfree male lifespan was also assessed. Changes in fly-associated microbial composition as a result of food pH were determined by 16S ribosomal RNA gene sequencing. Male gustatory responses, total consumption, and male and female longevity were additionally measured in the taste-defective Pox neuro (Poxn) mutant and its transgenic rescue control. An acidic diet increased Drosophila gustatory responses (40-230%) and food intake (5-50%) and extended survival (10-160% longer median lifespan) compared with flies on either neutral or alkaline pH food. Alkaline food pH shifted the composition of fly-associated bacteria and resulted in greater lifespan extension (260% longer median survival) after microbes were eliminated compared with flies on an acidic (50%) or neutral (130%) diet. However, germfree flies lived longer on an acidic diet (5-20% longer median lifespan) compared with those on either neutral or alkaline pH food. Gustatory responses, total consumption, and longevity were unaffected by food pH in Poxn mutant flies. Food pH can directly influence palatability and feeding behavior and affect parameters such as microbial growth to ultimately affect Drosophila lifespan. Fundamental food properties altered by dietary or drug interventions may therefore contribute to changes in animal physiology, metabolism, and survival. © 2015 American Society for Nutrition.

  18. Reevaluation of whether a soma-to-germ-line transformation extends lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Knutson, Andrew Kekūpa'a; Rechtsteiner, Andreas; Strome, Susan

    2016-03-29

    The germ lineage is considered to be immortal. In the quest to extend lifespan, a possible strategy is to drive germ-line traits in somatic cells, to try to confer some of the germ lineage's immortality on the somatic body. Notably, a study in Caenorhabditis elegans suggested that expression of germ-line genes in the somatic cells of long-lived daf-2 mutants confers some of daf-2's long lifespan. Specifically, mRNAs encoding components of C. elegans germ granules (P granules) were up-regulated in daf-2 mutant worms, and knockdown of individual P-granule and other germ-line genes in daf-2 young adults modestly reduced their lifespan. We investigated the contribution of a germ-line program to daf-2's long lifespan and also tested whether other mutants known to express germ-line genes in their somatic cells are long-lived. Our key findings are as follows. (i) We could not detect P-granule proteins in the somatic cells of daf-2 mutants by immunostaining or by expression of a P-granule transgene. (ii) Whole-genome transcript profiling of animals lacking a germ line revealed that germ-line transcripts are not up-regulated in the soma of daf-2 worms compared with the soma of control worms. (iii) Simultaneous removal of multiple P-granule proteins or the entire germ-line program from daf-2 worms did not reduce their lifespan. (iv) Several mutants that robustly express a broad spectrum of germ-line genes in their somatic cells are not long-lived. Together, our findings argue against the hypothesis that acquisition of a germ-cell program in somatic cells increases lifespan and contributes to daf-2's long lifespan.

  19. Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun, E-mail: lijunzhou@tju.edu.cn

    2015-12-25

    Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

  20. Estimation of obsolete cellular phones generation: A case study of China.

    Science.gov (United States)

    Guo, Xueyi; Yan, Kang

    2017-01-01

    Rapid development of electronic technique has led to decreasing lifespan of electronic products. Meanwhile, the amount of waste electrical and electronic equipment (WEEE) is rapidly growing in recent years especially in China. The generation amount of WEEE is one of the basic information for waste management. In our study, the generation of obsolete cellular phones and metals containing of cellular phones were estimated from 1997 to 2025. The future average possession in per 100 inhabitants of cellular phones was predicted using logistic model. Moreover, the lifespan distribution of cellular phones was analyzed using Weibull distribution. Meanwhile, the generation amount of obsolete cellular phones and its metals containing were estimated by using population balance model (PBM) and substance flow analysis (SFA), respectively. The estimated results indicate that the average possession in per 100 inhabitants will reach to 111.2 and 118.3 units in 2020 and 2025, respectively, which is about two times higher than the average possession in 2010. In addition, the total possession amount of cellular phones are expected to exceed 1.64 billion units in 2025. Moreover, the estimated results show that 781 million units obsolete cellular phones were generated in 2015, and the number will grow up to 877 and 937 million units in 2020 and 2025, respectively. In 2025, the total weight of annual generation amount of obsolete cellular phones will exceed 140Gg. The precious metals such as silver, gold contains in obsolete cellular phones will reach 56,250 and 28,130kg, respectively, in 2025. The obsolete cellular phones are the typical secondary metal resources especially for precious metals. In order to improve the recycling efficiency, it is necessary to establish a comprehensive system of waste management. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Overexpression of Fatty-Acid-β-Oxidation-Related Genes Extends the Lifespan of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Shin-Hae Lee

    2012-01-01

    Full Text Available A better understanding of the aging process is necessary to ensure that the healthcare needs of an aging population are met. With the trend toward increased human life expectancies, identification of candidate genes affecting the regulation of lifespan and its relationship to environmental factors is essential. Through misexpression screening of EP mutant lines, we previously isolated several genes extending lifespan when ubiquitously overexpressed, including the two genes encoding the fatty-acid-binding protein and dodecenoyl-CoA delta-isomerase involved in fatty-acid β-oxidation, which is the main energy resource pathway in eukaryotic cells. In this study, we analyzed flies overexpressing the two main components of fatty-acid β-oxidation, and found that overexpression of fatty-acid-β-oxidation-related genes extended the Drosophila lifespan. Furthermore, we found that the ability of dietary restriction to extend lifespan was reduced by the overexpression of fatty-acid-β-oxidation-related genes. Moreover, the overexpression of fatty-acid-β-oxidation-related genes enhanced stress tolerance to oxidative and starvation stresses and activated the dFOXO signal, indicating translocation to the nucleus and transcriptional activation of the dFOXO target genes. Overall, the results of this study suggest that overexpression of fatty-acid-β-oxidation-related genes extends lifespan in a dietary-restriction-related manner, and that the mechanism of this process may be related to FOXO activation.

  2. Rhodiola rosea extends lifespan and improves stress tolerance in silkworm, Bombyx mori.

    Science.gov (United States)

    Chen, Cong; Song, Jiangbo; Chen, Min; Li, Zhiquan; Tong, Xiaoling; Hu, Hai; Xiang, Zhonghuai; Lu, Cheng; Dai, Fangyin

    2016-04-01

    The root of Rhodiola rosea is widely used in Traditional Chinese Medicine. The extract from R. rosea is reported to extend the lifespan of yeast, nematode, and fruit fly. However, the molecular mechanism is not fully understood. Here, we tested whether R. rosea extends the lifespan of the silkworm. An aqueous extract of R. rosea significantly prolonged the lifespan of the silkworm, without affecting its daily food intake, body weight, or fecundity, suggesting that R. rosea did not exhibit obvious side effects. Rhodiola rosea extract also enhanced the stress resistance in the silkworm, against heat stress (37 °C) and starvation. The R. rosea extract increased the activity of the major antioxidant enzymes, glutathione S-transferase and catalase, and altered the content of glutathione and malondialdehyde. Rhodiola rosea increased the expression of BmFoxO, which is a downstream regulator of insulin/IGF-1 signaling (IIS) pathway in the silkworm. Our results showed that R. rosea extends lifespan, in which IIS pathway might be involved, and enhances stress resistance in the silkworm. Thus, the silkworm might be used as a novel animal model for lifespan study and efficacy evaluation of Traditional Chinese Medicines.

  3. Coffee, its roasted form, and their residues cause birth failure and shorten lifespan in dengue vectors.

    Science.gov (United States)

    Dieng, Hamady; Ellias, Salbiah Binti; Satho, Tomomitsu; Ahmad, Abu Hassan; Abang, Fatimah; Ghani, Idris Abd; Noor, Sabina; Ahmad, Hamdan; Zuharah, Wan Fatma; Morales Vargas, Ronald E; Morales, Noppawan P; Hipolito, Cirilo N; Attrapadung, Siriluck; Noweg, Gabriel Tonga

    2017-06-01

    In dengue mosquitoes, successful embryonic development and long lifespan are key determinants for the persistence of both virus and vector. Therefore, targeting the egg stage and vector lifespan would be expected to have greater impacts than larvicides or adulticides, both strategies that have lost effectiveness due to the development of resistance. Therefore, there is now a pressing need to find novel chemical means of vector control. Coffee contains many chemicals, and its waste, which has become a growing environmental concern, is as rich in toxicants as the green coffee beans; these chemicals do not have a history of resistance in insects, but some are lost in the roasting process. We examined whether exposure to coffee during embryonic development could alter larval eclosion and lifespan of dengue vectors. A series of bioassays with different coffee forms and their residues indicated that larval eclosion responses of Aedes albopictus and Ae. aegypti were appreciably lower when embryonic maturation occurred in environments containing coffee, especially roasted coffee crude extract (RCC). In addition, the lifespan of adults derived from eggs that hatched successfully in a coffee milieu was reduced, but this effect was less pronounced with roasted and green coffee extracts (RCU and GCU, respectively). Taken together, these findings suggested that coffee and its residues have embryocidal activities with impacts that are carried over onto the adult lifespan of dengue vectors. These effects may significantly reduce the vectorial capacity of these insects. Reutilizing coffee waste in vector control may also represent a realistic solution to the issues associated with its pollution.

  4. Control of lifespan by food bacteria, nutrient limitation and pathogenicity of food in C. elegans.

    Science.gov (United States)

    So, Shuhei; Tokumaru, Takaaki; Miyahara, Kohji; Ohshima, Yasumi

    2011-04-01

    The increased lifespan caused by food limitation has been observed in a wide range of animals including the nematode Caenorhabditis elegans. We show here that the lifespans of eat-2 and eat-5 feeding-defective mutants and a mutant of dbl-1 encoding a TGFβ ligand significantly change between the cultures fed on Escherichia coli strain OP50 or a more nutrient-rich strain HB101. On HB101 food, the eat-2, eat-5 and dbl-1 mutants show increased lifespan compared to that of the wild type. This result is probably due to nutrient limitation because the eat mutations reduce food uptake and the mutation of dbl-1 that regulates expression of several digestive enzymes leads to nutrient limitation. In contrast, the lifespans of the eat-2 and dbl-1 mutants decreased from that of the wild type on OP50 food. We found that live OP50 cells within a worm were markedly more in these mutants than in the wild type, which suggests that impaired digestion of pathogenic OP50 decreased lifespan in the eat-2 and dbl-1 mutants.

  5. Lonidamine extends lifespan of adult Caenorhabditis elegans by increasing the formation of mitochondrial reactive oxygen species.

    Science.gov (United States)

    Schmeisser, S; Zarse, K; Ristow, M

    2011-09-01

    Compounds that delay aging in model organisms may be of significant interest to antiaging medicine, since these substances potentially provide pharmaceutical approaches to promote healthy lifespan in humans. The aim of the study was to test whether pharmaceutical concentrations of the glycolytic inhibitor lonidamine are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Several hundreds of adult C. elegans roundworms were maintained on agar plates and fed E. coli strain OP50 bacteria. Lonidamine was applied to test whether it may promote longevity by quantifying survival in the presence and absence of the compound. In addition, several biochemical and metabolic assays were performed with nematodes exposed to lonidamine. Lonidamine significantly extends both median and maximum lifespan of C. elegans when applied at a concentration of 5 micromolar by 8% each. Moreover, the compound increases paraquat stress resistance, and promotes mitochondrial respiration, culminating in increased formation of reactive oxygen species (ROS). Extension of lifespan requires activation of pmk-1, an orthologue of p38 MAP kinase, and is abolished by co-application of an antioxidant, indicating that increased ROS formation is required for the extension of lifespan by lonidamine. Consistent with the concept of mitohormesis, lonidamine is capable of promoting longevity in a pmk-1 sensitive manner by increasing formation of ROS.

  6. Elucidating the Mechanism of Weissella-dependent Lifespan Extension in Caenorhabditis elegans.

    Science.gov (United States)

    Lee, Jiyun; Kwon, Gayeung; Lim, Young-Hee

    2015-11-25

    The mechanism whereby lactic acid bacteria extend the lifespan of Caenorhabditis elegans has previously been elucidated. However, the role of Weissella species has yet not been studied. We show that Weissella koreensis and Weissella cibaria significantly (p OP50 and induce the expression of several genes related to lifespan extension (daf-16, aak-2, jnk-1, sod-3 and hif-1). Oral administration of Weissella altered reactive oxygen species (ROS) production and lowered the accumulation of lipofuscin and increased locomotor activity (which translates to a delay in ageing). Moreover, Weissella-fed C. elegans had decreased body sizes, brood sizes, ATP levels and pharyngeal pumping rates compared with E. coli OP50-fed worms. Furthermore, mutations in sod-3, hif-1 or skn-1 did not alter lifespan extension compared with wild-type C. elegans. However, C. elegans failed to display lifespan extension in loss-of-function mutants of daf-16, aak-2 and jnk-1, which highlights the potential role of these genes in Weissella-induced longevity in C. elegans. Weissella species extend C. elegans lifespan by activating DAF-16 via the c-Jun N-terminal kinase (JNK) pathway, which is related to stress response, and the AMP-activated protein kinase (AMPK)-pathway that is activated by dietary restriction.

  7. Aspirin increases metabolism through germline signalling to extend the lifespan of Caenorhabditis elegans.

    Science.gov (United States)

    Huang, Xiao-Bing; Mu, Xiao-Hui; Wan, Qin-Li; He, Xiao-Ming; Wu, Gui-Sheng; Luo, Huai-Rong

    2017-01-01

    Aspirin is a prototypic cyclooxygenase inhibitor with a variety of beneficial effects on human health. It prevents age-related diseases and delays the aging process. Previous research has shown that aspirin might act through a dietary restriction-like mechanism to extend lifespan. To explore the mechanism of action of aspirin on aging, we determined the whole-genome expression profile of Caenorhabditis elegans treated with aspirin. Transcriptome analysis revealed the RNA levels of genes involved in metabolism were primarily increased. Reproduction has been reported to be associated with metabolism. We found that aspirin did not extend the lifespan or improve the heat stress resistance of germline mutants of glp-1. Furthermore, Oil Red O staining showed that aspirin treatment decreased lipid deposition and increased expression of lipid hydrolysis and fatty acid β-oxidation-related genes. The effect of germline ablation on lifespan was mainly mediated by DAF-12 and DAF-16. Next, we performed genetic analysis with a series of worm mutants and found that aspirin did not further extend the lifespans of daf-12 and daf-16 single mutants, glp-1;daf-12 and glp-1;daf-16 double mutants, or glp-1;daf-12;daf-16 triple mutants. The results suggest that aspirin increase metabolism and regulate germline signalling to activate downstream DAF-12 and DAF-16 to extend lifespan.

  8. Caenorhabditis elegans battling starvation stress: low levels of ethanol prolong lifespan in L1 larvae.

    Directory of Open Access Journals (Sweden)

    Paola V Castro

    Full Text Available The nematode Caenorhabditis elegans arrests development at the first larval stage if food is not present upon hatching. Larvae in this stage provide an excellent model for studying stress responses during development. We found that supplementing starved larvae with ethanol markedly extends their lifespan within this L1 diapause. The effects of ethanol-induced lifespan extension can be observed when the ethanol is added to the medium at any time between 0 and 10 days after hatching. The lowest ethanol concentration that extended lifespan was 1 mM (0.005%; higher concentrations to 68 mM (0.4% did not result in increased survival. In spite of their extended survival, larvae did not progress to the L2 stage. Supplementing starved cultures with n-propanol and n-butanol also extended lifespan, but methanol and isopropanol had no measurable effect. Mass spectrometry analysis of nematode fatty acids and amino acids revealed that L1 larvae can incorporate atoms from ethanol into both types of molecules. Based on these data, we suggest that ethanol supplementation may extend the lifespan of L1 larvae by either serving as a carbon and energy source and/or by inducing a stress response.

  9. Functional divergence of dafachronic acid pathways in the control of C. elegans development and lifespan.

    Science.gov (United States)

    Dumas, Kathleen J; Guo, Chunfang; Wang, Xi; Burkhart, Kirk B; Adams, Elizabeth J; Alam, Hena; Hu, Patrick J

    2010-04-15

    Steroid hormone and insulin/insulin-like growth factor signaling (IIS) pathways control development and lifespan in the nematode Caenorhabditis elegans by regulating the activity of the nuclear receptor DAF-12 and the FoxO transcription factor DAF-16, respectively. The DAF-12 ligands Delta(4)- and Delta(7)-dafachronic acid (DA) promote bypass of the dauer diapause and proper gonadal migration during larval development; in adults, DAs influence lifespan. Whether Delta(4)- and Delta(7)-DA have unique biological functions is not known. We identified the 3-beta-hydroxysteroid dehydrogenase (3betaHSD) family member HSD-1, which participates in Delta(4)-DA biosynthesis, as an inhibitor of DAF-16/FoxO activity. Whereas IIS promotes the cytoplasmic sequestration of DAF-16/FoxO, HSD-1 inhibits nuclear DAF-16/FoxO activity without affecting DAF-16/FoxO subcellular localization. Thus, HSD-1 and IIS inhibit DAF-16/FoxO activity via distinct and complementary mechanisms. In adults, HSD-1 was required for full lifespan extension in IIS mutants, indicating that HSD-1 interactions with IIS are context-dependent. In contrast to the Delta(7)-DA biosynthetic enzyme DAF-36, HSD-1 is dispensable for proper gonadal migration and lifespan extension induced by germline ablation. These findings provide insights into the molecular interface between DA and IIS pathways and suggest that Delta(4)- and Delta(7)-DA pathways have unique as well as overlapping biological functions in the control of development and lifespan.

  10. Triclosan (TCS) and Triclocarban (TCC) cause lifespan reduction and reproductive impairment through oxidative stress-mediated expression of the defensome in the monogonont rotifer (Brachionus koreanus).

    Science.gov (United States)

    Han, Jeonghoon; Won, Eun-Ji; Hwang, Un-Ki; Kim, Il-Chan; Yim, Joung Han; Lee, Jae-Seong

    2016-01-01

    Triclosan (TCS) and Triclocarban (TCC) are used as antimicrobial agents and have been widely dispersed and detected in the marine environment. However, the toxicities of TCS and TCC have been poorly investigated in marine invertebrates. In this study, the effects of TCS and TCC on mortality, population growth, lifespan, and fecundity were examined in the monogonont rotifer (Brachionus koreanus) using cellular ROS levels, GST enzymatic activity, and gene expression of defensomes. The median lethal concentration (LC50) of TCS (393.1μg/L) and TCC (388.1μg/L) was also determined in the same species. In TCS- and TCC-exposed B. koreanus, growth retardation and reduced fecundity were observed and were shown to have a potentially deleterious effect on the life cycle of B. koreanus. In addition, time-dependent increases in ROS content (%) and GST enzymatic activity were shown in response to TCS and TCC exposure. Additionally, transcript levels of detoxification proteins (e.g., CYPs), antioxidant proteins (e.g., GST-sigma, Cu/ZnSOD, CAT), and heat shock proteins (Hsps) were modulated in response to TCS and TCC exposure over a 24h period. Our results indicate that TCS and TCC induce oxidative stress and transcriptional regulation of detoxification, antioxidant, and heat shock proteins, resulting in changes in lifespan and fecundity.

  11. Nutritional Programming of Lifespan by FOXO Inhibition on Sugar-Rich Diets

    Directory of Open Access Journals (Sweden)

    Adam J. Dobson

    2017-01-01

    Full Text Available Consumption of unhealthy diets is exacerbating the burden of age-related ill health in aging populations. Such diets can program mammalian physiology to cause long-term, detrimental effects. Here, we show that, in Drosophila melanogaster, an unhealthy, high-sugar diet in early adulthood programs lifespan to curtail later-life survival despite subsequent dietary improvement. Excess dietary sugar promotes insulin-like signaling, inhibits dFOXO—the Drosophila homolog of forkhead box O (FOXO transcription factors—and represses expression of dFOXO target genes encoding epigenetic regulators. Crucially, dfoxo is required both for transcriptional changes that mark the fly’s dietary history and for nutritional programming of lifespan by excess dietary sugar, and this mechanism is conserved in Caenorhabditis elegans. Our study implicates FOXO factors, the evolutionarily conserved determinants of animal longevity, in the mechanisms of nutritional programming of animal lifespan.

  12. Rapamycin doses sufficient to extend lifespan do not compromise muscle mitochondrial content or endurance

    DEFF Research Database (Denmark)

    Widlund, Anne Lykkegaard; Vang, Ole; Ye, Lan;

    2013-01-01

    Rapamycin extends lifespan in mice, but can have a number of undesirable effects that may ultimately limit its utility in humans. The canonical target of rapamycin, and the one thought to account for its effects on lifespan, is the mammalian/mechanistic target of rapamycin, complex 1 (mTORC1). We...... have previously shown that at least some of the detrimental side effects of rapamycin are due to "off target" disruption of mTORC2, suggesting they could be avoided by more specific targeting of mTORC1. However, mTORC1 inhibitionper se can reduce the mRNA expression of mitochondrial genes...... and compromise the function of mitochondria in cultured muscle cells, implying that defects in bioenergetics might be an unavoidable consequence of targeting mTORC1 in vivo. Therefore, we tested whether rapamycin, at the same doses used to extend lifespan, affects mitochondrial function in skeletal muscle. While...

  13. Age-dependent changes in mitochondrial morphology and volume are not predictors of lifespan.

    Science.gov (United States)

    Regmi, Saroj G; Rolland, Stéphane G; Conradt, Barbara

    2014-02-01

    Mitochondrial dysfunction is a hallmark of skeletal muscle degeneration during aging. One mechanism through which mitochondrial dysfunction can be caused is through changes in mitochondrial morphology. To determine the role of mitochondrial morphology changes in age-dependent mitochondrial dysfunction, we studied mitochondrial morphology in body wall muscles of the nematodeC. elegans. We found that in this tissue, animals display a tubular mitochondrial network, which fragments with increasing age. This fragmentation is accompanied by a decrease in mitochondrial volume. Mitochondrial fragmentation and volume loss occur faster under conditions that shorten lifespan and occur slower under conditions that increase lifespan. However, neither mitochondrial morphology nor mitochondrial volume of five- and seven-day old wild-type animals can be used to predict individual lifespan. Our results indicate that while mitochondria in body wall muscles undergo age-dependent fragmentation and a loss in volume, these changes are not the cause of aging but rather a consequence of the aging process.

  14. Extended life-span conferred by cotransporter gene mutations in Drosophila.

    Science.gov (United States)

    Rogina, B; Reenan, R A; Nilsen, S P; Helfand, S L

    2000-12-15

    Aging is genetically determined and environmentally modulated. In a study of longevity in the adult fruit fly, Drosophila melanogaster, we found that five independent P-element insertional mutations in a single gene resulted in a near doubling of the average adult life-span without a decline in fertility or physical activity. Sequence analysis revealed that the product of this gene, named Indy (for I'm not dead yet), is most closely related to a mammalian sodium dicarboxylate cotransporter-a membrane protein that transports Krebs cycle intermediates. Indy was most abundantly expressed in the fat body, midgut, and oenocytes: the principal sites of intermediary metabolism in the fly. Excision of the P element resulted in a reversion to normal life-span. These mutations may create a metabolic state that mimics caloric restriction, which has been shown to extend life-span.

  15. Statin treatment increases lifespan and improves cardiac health in Drosophila by decreasing specific protein prenylation.

    Directory of Open Access Journals (Sweden)

    Stephen R Spindler

    Full Text Available Statins such as simvastatin are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase inhibitors and standard therapy for the prevention and treatment of cardiovascular diseases in mammals. Here we show that simvastatin significantly increased the mean and maximum lifespan of Drosophila melanogaster (Drosophila and enhanced cardiac function in aging flies by significantly reducing heart arrhythmias and increasing the contraction proportion of the contraction/relaxation cycle. These results appeared independent of internal changes in ubiquinone or juvenile hormone levels. Rather, they appeared to involve decreased protein prenylation. Simvastatin decreased the membrane association (prenylation of specific small Ras GTPases in mice. Both farnesyl (L744832 and type 1 geranylgeranyl transferase (GGTI-298 inhibitors increased Drosophila lifespan. These data are the most direct evidence to date that decreased protein prenylation can increase cardiac health and lifespan in any metazoan species, and may explain the pleiotropic (non-cholesterol related health effects of statins.

  16. Trichostatin A Extends the Lifespan of Drosophila melanogaster by Elevating hsp22 Expression

    Institute of Scientific and Technical Information of China (English)

    Dan TAO; Jun LU; Hui SUN; Yan-Mei ZHAO; Zhi-Gen YUAN; Xiao-Xue LI; Bai-Qu HUANG

    2004-01-01

    The level of acetylation of histones in nucleosomes is related to the longevity of yeast and animals. However, the mechanisms by which acetylation and deacetylation affect longevity remain unclear.In present study, we investigated the influence of histone acetylation modification on the expression of hsp22gene and the lifespan in Drosophila melanogaster using histone deacetylase (HDAC) inhibitor Trichostatin A (TSA). The results showed that TSA could extend the lifespan of Drosophila melanogaster. Furthermore,TSA significantly promoted the hsp22 gene transcription, and affected the chromatin morphology at the locus of hsp22 gene along the polytene chromosome. Present data implicate that TSA may affect the lifespan of Drosophila through changing the level of histone acetylation and influencing the expression of hsp22 gene that is related to aging.

  17. Lifespan divergence between social insect castes: challenges and opportunities for evolutionary theories of aging.

    Science.gov (United States)

    Kramer, Boris H; van Doorn, G Sander; Weissing, Franz J; Pen, Ido

    2016-08-01

    The extraordinarily long lifespans of queens (and kings) in eusocial insects and the strikingly large differences in life expectancy between workers and queens challenge our understanding of the evolution of aging and provide unique opportunities for studying the causes underlying adaptive variation in lifespan within species. Here we review the major evolutionary theories of aging, focusing on their scope and limitations when applied to social insects. We show that reproductive division of labor, interactions between kin, caste-specific gene regulation networks, and the integration of colony-level trade-offs with individual-level trade-offs provide challenges to the classical theories We briefly indicate how these challenges could be met in future models of adaptive phenotypic plasticity in lifespan between and within different castes. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Reversible quantum cellular automata

    CERN Document Server

    Schumacher, B

    2004-01-01

    We define quantum cellular automata as infinite quantum lattice systems with discrete time dynamics, such that the time step commutes with lattice translations and has strictly finite propagation speed. In contrast to earlier definitions this allows us to give an explicit characterization of all local rules generating such automata. The same local rules also generate the global time step for automata with periodic boundary conditions. Our main structure theorem asserts that any quantum cellular automaton is structurally reversible, i.e., that it can be obtained by applying two blockwise unitary operations in a generalized Margolus partitioning scheme. This implies that, in contrast to the classical case, the inverse of a nearest neighbor quantum cellular automaton is again a nearest neighbor automaton. We present several construction methods for quantum cellular automata, based on unitaries commuting with their translates, on the quantization of (arbitrary) reversible classical cellular automata, on quantum c...

  19. A C-terminal truncated mutation of spr-3 gene extends lifespan in Caenorhabditis elegans

    Institute of Scientific and Technical Information of China (English)

    Ping Yang; Ruilin Sun; Minghui Yao; Weidong Chen; Zhugang Wang; Jian Fei

    2013-01-01

    The lifespan of Caenorhabditis elegans is determined by various genetic and environmental factors.In this paper,spr-3,a C.elegans homologous gene of the mammalian neural restrictive silencing factor (NRSF/REST),is reported to be an important gene regulating lifespan of C.elegans.A deletion mutation ofspr-3,spr-3(ok2525),or RNAi inhibition of spr-3 expression led to the short lifespan phenotype in C.elegans.However,a nonsense mutation of spr-3,spr3(by108),increased the lifespan by 26% when compared with that of wild-type nematode.The spr-3(by108) also showed increased resistance to environmental stress.The spr-3(by108) mutated gene encodes a C-terminal truncated protein with a structure comparable with the REST4,a splice variant of the NRSF/REST in mammalian.The long lifespan phenotype of spr-3(by108) mutant is confirmed as a gain of function and dependent on normal functions of daf16 and glp-1.The lifespan of the spr-3(by108) can be synergistically enhanced by inducing a mutation in daf-2.Quantitative polymerase chain reaction results showed that the expression of daf-16 as well as its target gene sod-3,mtl1,and sip-1 was up-regulated in the spr-3(by108) mutant.These results would be helpful to further understand the complex function of NRSF/REST gene in mammalian,especially in the aging process and longevity determination.

  20. A Modified Carbon Monoxide Breath Test for Measuring Erythrocyte Lifespan in Small Animals

    Directory of Open Access Journals (Sweden)

    Yong-Jian Ma

    2016-01-01

    Full Text Available This study was to develop a CO breath test for RBC lifespan estimation of small animals. The ribavirin induced hemolysis rabbit models were placed individually in a closed rebreath cage and air samples were collected for measurement of CO concentration. RBC lifespan was calculated from accumulated CO, blood volume, and hemoglobin concentration data. RBC lifespan was determined in the same animals with the standard biotin-labeling method. RBC lifespan data obtained by the CO breath test method for control (CON, 49.0±5.9 d rabbits, rabbits given 10 mg/kg·d−1 of ribavirin (RIB10, 31.0±4.0 d, and rabbits given 20 mg/kg·d−1 of ribavirin (RIB20, 25.0±2.9 d were statistically similar (all p>0.05 to and linearly correlated (r=0.96, p<0.01 with the RBC lifespan data obtained for the same rabbits by the standard biotin-labeling method (CON, 51.0±2.7 d; RIB10, 33.0±1.3 d; and RIB20, 27.0±0.8 d. The CO breath test method takes less than 3 h to complete, whereas the standard method requires at least several weeks. In conclusion, the CO breath test method provides a simple and rapid means of estimating RBC lifespan and is feasible for use with small animal models.

  1. Antioxidants can extend lifespan of Brachionus manjavacas (Rotifera), but only in a few combinations

    Science.gov (United States)

    Fields, Allison M.; Johnston, Rachel K.

    2013-01-01

    Animal cells are protected from oxidative damage by an antioxidant network operating as a coordinated system, with strong synergistic interactions. Lifespan studies with whole animals are expensive and laborious, so there has been little investigation of which antioxidant interactions might be useful for life extension. Animals in the phylum Rotifera are particularly promising models for aging studies because they are small (0.1–1 mm), have short, two-week lifespan, display typical patterns of animal aging, and have well characterized, easy to measure phenotypes of aging and senescence. One class of interventions that has consistently produced significant rotifer life extension is antioxidants. Although the mechanism of antioxidant effects on animal aging remains controversial, the ability of some antioxidant supplements to extend rotifer lifespan was unequivocal. We found that exposing rotifers to certain combinations of antioxidant supplements can produce up to about 20% longer lifespan, but that most antioxidants have no effect. We performed life table tests with 20 single antioxidants and none yielded significant rotifer life extension. We tested 60 two-way combinations of selected antioxidants and only seven (12%) produced significant rotifer life extension. None of the 20 three- and four-way antioxidant combinations tested yielded significant rotifer life extension. These observations suggest that dietary exposure of antioxidants can extend rotifer lifespan, but most antioxidants do not. We observed significant rotifer life extension only when antioxidants were paired with trolox, N-acetyl cysteine, l-carnosine, or EUK-8. This illustrates that antioxidant treatments capable of rotifer life extension are patchily distributed in the parameter space, so large regions must be searched to find them. It furthermore underscores the value of the rotifer model to conduct rapid, facile life table experiments with many treatments, which makes such a search feasible

  2. Effects of the mitochondria-targeted antioxidant SkQ1 on lifespan of rodents

    Science.gov (United States)

    Anisimov, Vladimir N.; Egorov, Maxim V.; Krasilshchikova, Marina S.; Lyamzaev, Konstantin G.; Manskikh, Vasily N.; Moshkin, Mikhail P.; Novikov, Evgeny A.; Popovich, Irina G.; Rogovin, Konstantin A.; Shabalina, Irina G.; Shekarova, Olga N.; Skulachev, Maxim V.; Titova, Tatiana V.; Vygodin, Vladimir A.; Vyssokikh, Mikhail Yu.; Yurova, Maria N.; Zabezhinsky, Mark A.; Skulachev, Vladimir P.

    2011-01-01

    The effect of the mitochondria-targeted, plastoquinone-containing antioxidant SkQ1 on the lifespan of outbred mice and of three strains of inbred mice was studied. To this end, low pathogen (LP) or specific pathogen free (SPF) vivaria in St. Petersburg, Moscow, and Stockholm were used. For comparison, we also studied mole-voles and dwarf hamsters, two wild species of small rodents kept under simulated natural conditions. It was found that substitution of a LP vivarium for a conventional (non-LP) one doubled the lifespan of female outbred mice, just as SkQ1 did in a non-LP vivarium. SkQ1 prevented age-dependent disappearance of estrous cycles of outbred mice in both LP and non-LP vivaria. In the SPF vivarium in Moscow, male BALB/c mice had shorter lifespan than females, and SkQ1 increased their lifespan to the values of the females. In the females, SkQ1 retarded development of such trait of aging as heart mass increase. Male C57Bl/6 mice housed individually in the SPF vivarium in Stockholm lived as long as females. SkQ1 increased the male lifespan, the longevity of the females being unchanged. SkQ1 did not change food intake by these mice. Dwarf hamsters and mole-voles kept in outdoor cages or under simulated natural conditions lived longer if treated with SkQ1. The effect of SkQ1 on longevity of females is assumed to mainly be due to retardation of the age-linked decline of the immune system. For males under LP or SPF conditions, SkQ1 increased the lifespan, affecting also some other system(s) responsible for aging. PMID:22166671

  3. The effects of seasonal, ontogenetic, and genetic factors on lifespan of male and female progeny of Arvicola amphibius

    Directory of Open Access Journals (Sweden)

    Galina eNazarova

    2013-06-01

    Full Text Available The water vole (Arvicola amphibius in the forest-steppe of West Siberia is known to have wide fluctuations in abundance. These fluctuations are accompanied by changes in birth and death rates, sex-age structure of the population, and individual morphophysiological and behavioral characteristics of the animals. Survival of the animals depends on season, phase of population cycle, and sex. Based on the data of long-term captive breeding of water voles, the maximal lifespan of males was found to be 1188 days and that of females, 1108 days. There were no differences between the sexes in mean lifespan. The probability of living 2 years or longer was 0.21. Individuals who began breeding at an older age had a significantly longer lifespan and produced more offspring. The survival curves of the spring-born animals were steeper than of those summer/autumn-born. Maternal factors had differential effect on males and females with respect to lifespan. Male lifespan correlated negatively with maternal age, parity, and litter size, whereas female lifespan did not correlate with these characteristics. To estimate heritability, parent-offspring correlations of a lifespan were calculated, as well as full-sib intraclass correlations. No statistically significant correlation was found between sons’ and maternal, sons’ and paternal, and daughters’ and paternal lifespans. Daughters’ lifespan correlated positively with maternal lifespan (r = 0.21, p < 0.001. Female full-sibs and male full-sibs had the same intraclass correlations, 0.22, p < 0.001. The differences between heritability estimates obtained by different methods may be explained by sex-specific genetic controls over lifespan and/or sex-specific effects of the environment.

  4. Mathematical Basis of Idea That Harmonious Marriage Can Lengthen Life-span

    Institute of Scientific and Technical Information of China (English)

    Zhi-qiang Zhang

    2009-01-01

    It is a very important issue for us to explore the effects of the marriage to life. In recent years, many scholars have proved that the marriage can lengthen life-span from different angles. With the development of theory of dependence random variables, we discuss the effects of the marriage to life and provide a mathematical basis of the idea that the harmonious marriage can lengthen life-span in this paper. Meanwhile, we analyze the impact of the marriage on life on the basis of the net single premium.

  5. The Impact of Endometriosis across the Lifespan of Women: Foreseeable Research and Therapeutic Prospects

    Directory of Open Access Journals (Sweden)

    C. L. Hughes

    2015-01-01

    Full Text Available In addition to estrogen dependence, endometriosis is characterized by chronic pelvic inflammation. The impact of the chronic pelvic inflammatory state on other organ systems and women’s health is unclear. Endometriosis associated chronic inflammation and potential adverse health effects across the lifespan render it imperative for renewed research vigor into the identification of novel biomarkers of disease and therapeutic options. Herein we propose a number of opportunities for research and development of new therapeutics to address the unmet needs in the treatment of endometriosis per se and its ancillary risks for other diseases in women across the lifespan.

  6. Life-span plasticity of the brain and cognition: from questions to evidence and back.

    Science.gov (United States)

    Raz, Naftali; Lindenberger, Ulman

    2013-11-01

    Experience-related changes induced by modification of environment, physical exercise, or cognitive training affect brain structure and function. Research on brain plasticity and its relationship to experiential changes gathers momentum and attracts significant public interest. This collection of papers is based on presentation at the First International Conference on Life-Span Plasticity of Brain and Behavior: A Cognitive Neuroscience Perspective that took place in Detroit, MI, on October 12-14, 2011. The conference honored Margret M. and Paul B. Baltes, the pioneers of life-span developmental psychology who initiated some of the first studies on experience- and training-related changes in cognition across the life span.

  7. High OCT4 and Low p16INK4A Expressions Determine In Vitro Lifespan of Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Carla A. Piccinato

    2015-01-01

    Full Text Available After long-term culture, mesenchymal stem cells alter their biological properties and enter into a state of replicative senescence. Although several classical biomarkers have been used for quantitative assessment of cellular senescence, no hallmark has been proven completely unique to the senescent state in cells. We used bone marrow-derived MSCs (BM-MSCs from different healthy young donors and an in vitro model with well-defined senescence end points to identify a set of robust markers that could potentially predict the expansion capacity of MSCs preparations before reaching senescence. For each early passage BM-MSC sample (5th or 6th passages, the normalized protein expression levels of senescence-associated markers p16INK4A, p21WAF1, SOD2, and rpS6S240/244; the concentration of IL6 and IL8 in cell culture supernatants; and the normalized gene expression levels of pluripotency markers OCT4, NANOG, and SOX2 were correlated with final population doubling (PD number. We revealed that the low expression of p16INK4A protein and a high OCT4 gene expression, rather than other evaluated markers, might be potential hallmarks and predictors of greater in vitro lifespan and growth potential, factors that can impact the successful therapeutic use of MSCs preparations.

  8. A computational model incorporating neural stem cell dynamics reproduces glioma incidence across the lifespan in the human population.

    Directory of Open Access Journals (Sweden)

    Roman Bauer

    Full Text Available Glioma is the most common form of primary brain tumor. Demographically, the risk of occurrence increases until old age. Here we present a novel computational model to reproduce the probability of glioma incidence across the lifespan. Previous mathematical models explaining glioma incidence are framed in a rather abstract way, and do not directly relate to empirical findings. To decrease this gap between theory and experimental observations, we incorporate recent data on cellular and molecular factors underlying gliomagenesis. Since evidence implicates the adult neural stem cell as the likely cell-of-origin of glioma, we have incorporated empirically-determined estimates of neural stem cell number, cell division rate, mutation rate and oncogenic potential into our model. We demonstrate that our model yields results which match actual demographic data in the human population. In particular, this model accounts for the observed peak incidence of glioma at approximately 80 years of age, without the need to assert differential susceptibility throughout the population. Overall, our model supports the hypothesis that glioma is caused by randomly-occurring oncogenic mutations within the neural stem cell population. Based on this model, we assess the influence of the (experimentally indicated decrease in the number of neural stem cells and increase of cell division rate during aging. Our model provides multiple testable predictions, and suggests that different temporal sequences of oncogenic mutations can lead to tumorigenesis. Finally, we conclude that four or five oncogenic mutations are sufficient for the formation of glioma.

  9. Effects on murine behavior and lifespan of selectively decreasing expression of mutant huntingtin allele by supt4h knockdown.

    Directory of Open Access Journals (Sweden)

    Hui-Min Cheng

    2015-03-01

    Full Text Available Production of protein containing lengthy stretches of polyglutamine encoded by multiple repeats of the trinucleotide CAG is a hallmark of Huntington's disease (HD and of a variety of other inherited degenerative neurological and neuromuscular disorders. Earlier work has shown that interference with production of the transcription elongation protein SUPT4H results in decreased cellular capacity to transcribe mutant huntingtin gene (Htt alleles containing long CAG expansions, but has little effect on expression of genes containing short CAG stretches. zQ175 and R6/2 are genetically engineered mouse strains whose genomes contain human HTT alleles that include greatly expanded CAG repeats and which are used as animal models for HD. Here we show that reduction of SUPT4H expression in brains of zQ175 mice by intracerebroventricular bolus injection of antisense 2'-O-methoxyethyl oligonucleotides (ASOs directed against Supt4h, or in R6/2 mice by deletion of one copy of the Supt4h gene, results in a decrease in mRNA and protein encoded specifically by mutant Htt alleles. We further show that reduction of SUPT4H in mouse brains is associated with decreased HTT protein aggregation, and in R6/2 mice, also with prolonged lifespan and delay of the motor impairment that normally develops in these animals. Our findings support the view that targeting of SUPT4H function may be useful as a therapeutic countermeasure against HD.

  10. Administration with Bushenkangshuai Tang alleviates UV irradiation- and oxidative stress-induced lifespan defects in nematode Caenorhabditis elegans

    Institute of Scientific and Technical Information of China (English)

    Qi RUI; Qin LU; Dayong WANG

    2009-01-01

    During normal metabolism, oxidative bypro-ducts will inevitably generate and damage molecules thereby impairing their biological functions, including the is a traditional Chinese medicine widely used for clini-cally treating premature ovarian failure. In the present study, BT administration at high concentrations signifi-cantly increased lifespan, slowed aging-related decline, and delayed accumulation of aging-related cellular damage in wild-type Caenorhabditis elegans. BT admin-istration could further largely alleviate the aging defects induced by UV and oxidative stresses, and BT administra-tion at different concentrations could largely rescue the aging defects in mev-1 mutant animals. The protective effects of BT administration on aging process were at least partially dependent on the Ins/IGF-like signaling pathway. Moreover, BT administration at different concentrations obviously altered the expression patterns of antioxidant genes and suppressed the severe stress responses induced by UV and oxidative stresses, suggesting that BT-induced tolerance to UV or oxidative stress might result from reactive oxygen species scavenging. BT administration during development was not necessarily a requirement for UV and oxidative stress resistance, and the concentrations of administrated BT examined were not toxic for nematodes. Therefore, BT administration could effectively retrieve the aging defects induced by UV irradiation and oxidative stress in Caenorhabditis elegans.

  11. Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials.

    Science.gov (United States)

    Kawasaki, Haruhisa; Guan, Jianjun; Tamama, Kenichi

    2010-07-02

    Cell therapy with bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) represents a promising approach in the field of regenerative medicine. Low frequency of MSCs in adult bone marrow necessitates ex vivo expansion of MSCs after harvest; however, such a manipulation causes cellular senescence with loss of differentiation, proliferative, and therapeutic potentials of MSCs. Hydrogen molecules have been shown to exert organ protective effects through selective reduction of hydroxyl radicals. As oxidative stress is one of the key insults promoting cell senescence in vivo as well as in vitro, we hypothesized that hydrogen molecules prevent senescent process during MSC expansion. Addition of 3% hydrogen gas enhanced preservation of colony forming early progenitor cells within MSC preparation and prolonged the in vitro replicative lifespan of MSCs without losing differentiation potentials and paracrine capabilities. Interestingly, 3% hydrogen gas treatment did not decrease hydroxyl radical, protein carbonyl, and 8-hydroxydeoxyguanosine, suggesting that scavenging hydroxyl radical might not be responsible for these effects of hydrogen gas in this study.

  12. Rewiring yeast acetate metabolism through MPC1 loss of function leads to mitochondrial damage and decreases chronological lifespan

    Directory of Open Access Journals (Sweden)

    Ivan Orlandi

    2014-11-01

    Full Text Available During growth on fermentable substrates, such as glucose, pyruvate, which is the end-product of glycolysis, can be used to generate acetyl-CoA in the cytosol via acetaldehyde and acetate, or in mitochondria by direct oxidative decarboxylation. In the latter case, the mitochondrial pyruvate carrier (MPC is responsible for pyruvate transport into mitochondrial matrix space. During chronological aging, yeast cells which lack the major structural subunit Mpc1 display a reduced lifespan accompanied by an age-dependent loss of autophagy. Here, we show that the impairment of pyruvate import into mitochondria linked to Mpc1 loss is compensated by a flux redirection of TCA cycle intermediates through the malic enzyme-dependent alternative route. In such a way, the TCA cycle operates in a “branched” fashion to generate pyruvate and is depleted of intermediates. Mutant cells cope with this depletion by increasing the activity of glyoxylate cycle and of the pathway which provides the nucleocytosolic acetyl-CoA. Moreover, cellular respiration decreases and ROS accumulate in the mitochondria which, in turn, undergo severe damage. These acquired traits in concert with the reduced autophagy restrict cell survival of the mpc1∆ mutant during chronological aging. Conversely, the activation of the carnitine shuttle by supplying acetyl-CoA to the mitochondria is sufficient to abrogate the short-lived phenotype of the mutant.

  13. Heterogeneous cellular networks

    CERN Document Server

    Hu, Rose Qingyang

    2013-01-01

    A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

  14. Every-other-day feeding extends lifespan but fails to delay many symptoms of aging in mice

    DEFF Research Database (Denmark)

    Xie, Kan; Neff, Frauke; Markert, Astrid

    2017-01-01

    Dietary restriction regimes extend lifespan in various animal models. Here we show that longevity in male C57BL/6J mice subjected to every-other-day feeding is associated with a delayed onset of neoplastic disease that naturally limits lifespan in these animals. We compare more than 200 phenotype...

  15. Evolution of product lifespan and implications for environmental assessment and management: a case study of personal computers in higher education.

    Science.gov (United States)

    Babbitt, Callie W; Kahhat, Ramzy; Williams, Eric; Babbitt, Gregory A

    2009-07-01

    Product lifespan is a fundamental variable in understanding the environmental impacts associated with the life cycle of products. Existing life cycle and materials flow studies of products, almost without exception, consider lifespan to be constant over time. To determine the validity of this assumption, this study provides an empirical documentation of the long-term evolution of personal computer lifespan, using a major U.S. university as a case study. Results indicate that over the period 1985-2000, computer lifespan (purchase to "disposal") decreased steadily from a mean of 10.7 years in 1985 to 5.5 years in 2000. The distribution of lifespan also evolved, becoming narrower over time. Overall, however, lifespan distribution was broader than normally considered in life cycle assessments or materials flow forecasts of electronic waste management for policy. We argue that these results suggest that at least for computers, the assumption of constant lifespan is problematic and that it is important to work toward understanding the dynamics of use patterns. We modify an age-structured model of population dynamics from biology as a modeling approach to describe product life cycles. Lastly, the purchase share and generation of obsolete computers from the higher education sector is estimated using different scenarios for the dynamics of product lifespan.

  16. Modeling cellular systems

    CERN Document Server

    Matthäus, Franziska; Pahle, Jürgen

    2017-01-01

    This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

  17. Epigenetics and Cellular Metabolism

    OpenAIRE

    Wenyi Xu; Fengzhong Wang; Zhongsheng Yu; Fengjiao Xin

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the proce...

  18. Nanostructured cellular networks.

    Science.gov (United States)

    Moriarty, P; Taylor, M D R; Brust, M

    2002-12-01

    Au nanocrystals spin-coated onto silicon from toluene form cellular networks. A quantitative statistical crystallography analysis shows that intercellular correlations drive the networks far from statistical equilibrium. Spin-coating from hexane does not produce cellular structure, yet a strong correlation is retained in the positions of nanocrystal aggregates. Mechanisms based on Marangoni convection alone cannot account for the variety of patterns observed, and we argue that spinodal decomposition plays an important role in foam formation.

  19. Dance Talent Development across the Lifespan: A Review of Current Research

    Science.gov (United States)

    Chua, Joey

    2014-01-01

    The aim of this study is to compile and synthesize empirically based articles published between 2000 and 2012 about the critical issues of developing dance talents across the lifespan of children, adolescents and adults. The present article updates and extends a review article related to the identification and development in dance written by…

  20. A bodyweight-dependent allometric exponent for scaling clearance across the human life-span

    NARCIS (Netherlands)

    C. Wang (Chenguang); M.Y. Peeters (Mariska); K. Allegaert (Karel); H.J. Blussé van Oud-Alblas (Heleen); E.H.J. Krekels (Elke); D. Tibboel (Dick); M. Danhof (Meindert); C.A.J. Knibbe (Catherijne)

    2012-01-01

    textabstractPurpose: To explore different allometric equations for scaling clearance across the human life-span using propofol as a model drug. Methods: Data from seven previously published propofol studies ((pre)term neonates, infants, toddlers, children, adolescents and adults) were analysed using

  1. Perceptions of Love across the Lifespan: Differences in Passion, Intimacy, and Commitment

    Science.gov (United States)

    Sumter, Sindy R.; Valkenburg, Patti M.; Peter, Jochen

    2013-01-01

    This study investigated perceptions of love across the lifespan using Sternberg's triangular theory of love, which distinguishes between passion, intimacy, and commitment. The study aimed to (a) investigate the psychometric properties of the short Triangular Love Scale (TLS-short) in adolescents and adults (see Appendix), and (b) track age…

  2. A bodyweight-dependent allometric exponent for scaling clearance across the human life-span

    NARCIS (Netherlands)

    C. Wang (Chenguang); M.Y. Peeters (Mariska); K. Allegaert (Karel); H.J. Blussé van Oud-Alblas (Heleen); E.H.J. Krekels (Elke); D. Tibboel (Dick); M. Danhof (Meindert); C.A.J. Knibbe (Catherijne)

    2012-01-01

    textabstractPurpose: To explore different allometric equations for scaling clearance across the human life-span using propofol as a model drug. Methods: Data from seven previously published propofol studies ((pre)term neonates, infants, toddlers, children, adolescents and adults) were analysed using

  3. Whole lifespan microscopic observation of budding yeast aging through a microfluidic dissection platform

    NARCIS (Netherlands)

    Lee, Sung Sik; Avalos Vizcarra, Ima; Huberts, Daphne H E W; Lee, Luke P; Heinemann, Matthias

    2012-01-01

    Important insights into aging have been generated with the genetically tractable and short-lived budding yeast. However, it is still impossible today to continuously track cells by high-resolution microscopic imaging (e.g., fluorescent imaging) throughout their entire lifespan. Instead, the field

  4. Lifespan metabolic potential of the unicellular organisms expressed by Boltzmann constant, absolute temperature and proton mass

    Science.gov (United States)

    Atanasov, Atanas Todorov

    2016-12-01

    The unicellular organisms and phages are the first appeared fundamental living organisms on the Earth. The total metabolic energy (Els, J) of these organisms can be expressed by their lifespan metabolic potential (Als, J/kg) and body mass (M, kg): Els =Als M. In this study we found a different expression - by Boltzmann's constant (k, J/K), nucleon mass (mp+, kg) of protons (and neutrons), body mass (M, kg) of organism or mass (Ms) of biomolecules (proteins, nucleotides, polysaccharides and lipids) building organism, and the absolute temperature (T, K). The found equations are: Els= (M/mp+)kT for phages and Els=(Ms/mp+)kT for the unicellular organisms. From these equations the lifespan metabolic potential can be expressed as: Als=Els/M= (k/mp+)T for phages and Als=Els/M= (k/3.3mp+)T for unicellular organisms. The temperature-normated lifespan metabolic potential (Als/T, J/K.kg) is equals to the ratio between Boltzmann's constant and nucleon mass: Als/T=k/mp+ for phages and Als/T=k/3.3mp+ for unicellular organisms. The numerical value of the k/mp+ ratio is equals to 8.254×103 J/K.kg, and the numerical value of k/3.3mp+ ratio is equal to 2.497×103 J/K.kg. These values of temperature-normated lifespan metabolic potential could be considered fundamental for the unicellular organisms.

  5. Lifespan divergence between social insect castes : Challenges and opportunities for evolutionary theories of aging

    NARCIS (Netherlands)

    Kramer, Boris H; van Doorn, G Sander; Weissing, Franz J; Pen, Ido

    2016-01-01

    The extraordinarily long lifespans of queens (and kings) in eusocial insects and the strikingly large differences in life expectancy between workers and queens challenge our understanding of the evolution of aging and provide unique opportunities for studying the causes underlying adaptive variation

  6. Aging and orthopedics: how a lifespan development model can inform practice and research.

    Science.gov (United States)

    Gautreau, Sylvia; Gould, Odette N; Forsythe, Michael E

    2016-08-01

    Orthopedic surgical care, like all health care today, is in flux owing to an aging population and to chronic medical conditions leading to an increased number of people with illnesses that need to be managed over the lifespan. The result is an ongoing shift from curing acute illnesses to the management and care of chronic illness and conditions. Theoretical models that provide a useful and feasible vision for the future of health care and health care research are needed. This review discusses how the lifespan development model used in some disciplines within the behavioural sciences can be seen as an extension of the biopsychosocial model. We posit that the lifespan development model provides useful perspectives for both orthopedic care and research. We present key concepts and recommendations, and we discuss how the lifespan development model can contribute to new and evolving perspectives on orthopedic outcomes and to new directions for research. We also offer practical guidelines on how to implement the model in orthopedic practice.

  7. Lifespan method as a tool to study criticality in absorbing-state phase transitions

    Science.gov (United States)

    Mata, Angélica S.; Boguñá, Marian; Castellano, Claudio; Pastor-Satorras, Romualdo

    2015-05-01

    In a recent work, a new numerical method (the lifespan method) has been introduced to study the critical properties of epidemic processes on complex networks [M. Boguñá, C. Castellano, and R. Pastor-Satorras, Phys. Rev. Lett. 111, 068701 (2013), 10.1103/PhysRevLett.111.068701]. Here, we present a detailed analysis of the viability of this method for the study of the critical properties of generic absorbing-state phase transitions in lattices. Focusing on the well-understood case of the contact process, we develop a finite-size scaling theory to measure the critical point and its associated critical exponents. We show the validity of the method by studying numerically the contact process on a one-dimensional lattice and comparing the findings of the lifespan method with the standard quasistationary method. We find that the lifespan method gives results that are perfectly compatible with those of quasistationary simulations and with analytical results. Our observations confirm that the lifespan method is a fully legitimate tool for the study of the critical properties of absorbing phase transitions in regular lattices.

  8. Investigating the life-span of cork products through a longitudinal approach with users- Interim results

    NARCIS (Netherlands)

    Da Silva Pereira, A.C.; Brezet, J.C.; Pereira, H.; Vogtlander, J.G.

    2012-01-01

    Products with long life-spans are generally preferred form an environmental perspective. This paper addresses the longevity of cork products, and the respective influencing aspects. This is accomplished through a longitudinal study where several cork products are used, and at different moments in ti

  9. Mental health and illness in relation to physical health across the lifespan

    NARCIS (Netherlands)

    Lamers, S.M.A.; Westerhof, Gerben Johan; Bohlmeijer, Ernst Thomas; Keyes, Corey L.M.; Sinnott, J.D.

    2013-01-01

    This chapter addresses mental health as more than the absence of disease, also approaching it from a positive perspective as the presence of well-being across the lifespan. The study described in the chapter investigated the association of age with psychopathology and positive mental health,

  10. Career Adaptability: An Integrative Construct for Life-Span, Life-Space Theory.

    Science.gov (United States)

    Savickas, Mark L.

    1997-01-01

    Examines the origin and current status of lifespan, life-space theory and proposes one way in which to integrate its three segments. Discusses a functionalist strategy for theory construction and the outcomes and consequences of this strategy. Discusses future directions for theory development, such as career adaptability and planful attitudes.…

  11. Myricetin-Mediated Lifespan Extension in Caenorhabditis elegans Is Modulated by DAF-16

    Directory of Open Access Journals (Sweden)

    Wim Wätjen

    2013-06-01

    Full Text Available Myricetin is a naturally occurring flavonol found in many plant based food sources. It increases the lifespan of Caenorhabditis elegans, but the molecular mechanisms are not yet fully understood. We have investigated the impact of this flavonoid on the transcription factors DAF-16 (C. elegans FoxO homologue and SKN-1 (Nrf2 homologue, which have crucial functions in the regulation of ageing. Myricetin is rapidly assimilated by the nematode, causes a nuclear translocation of DAF-16 but not of SKN-1, and finally prolongs the mean adult lifespan of C. elegans by 32.9%. The lifespan prolongation was associated with a decrease in the accumulation of reactive oxygen species (ROS detected by DCF. Myricetin also decreases the formation of lipofuscin, a pigment consisting of highly oxidized and cross-linked proteins that is considered as a biomarker of ageing in diverse species. The lifespan extension was completely abolished in a daf-16 loss-of-function mutant strain (CF1038. Consistently with this result, myricetin was also not able to diminish stress-induced ROS accumulation in the mutant. These results strongly indicate that the pro-longevity effect of myricetin is dependent on DAF-16 and not on direct anti-oxidative effects of the flavonoid.

  12. Epigenetic Effects of Diet on Fruit Fly Lifespan: An Investigation to Teach Epigenetics to Biology Students

    Science.gov (United States)

    Billingsley, James; Carlson, Kimberly A.

    2010-01-01

    Do our genes exclusively control us, or are other factors at play? Epigenetics can provide a means for students to use inquiry-based methods to understand a complex biological concept. Students research and design an experiment testing whether dietary supplements affect the lifespan of Drosophila melanogaster over multiple generations.

  13. Genetic and environmental stability in attention problems across the lifespan: evidence from the Netherlands Twin Register

    NARCIS (Netherlands)

    Kan, K.J.; Dolan, C.V.; Nivard, M.G.; Middeldorp, C.M.; van Beijsterveldt, C.E.M.; Willemsen, G.; Boomsma, D.I.

    2013-01-01

    Objective: To review findings on attention-deficit/hyperactivity disorder and attention problems (AP) in children, adolescents, and adults, as established in the database of the Netherlands Twin Register and increase the understanding of stability in AP across the lifespan as a function of genetic a

  14. Logic and Belief across the Lifespan: The Rise and Fall of Belief Inhibition during Syllogistic Reasoning

    Science.gov (United States)

    De Neys, Wim; Van Gelder, Elke

    2009-01-01

    Popular reasoning theories postulate that the ability to inhibit inappropriate beliefs lies at the heart of the human reasoning engine. Given that people's inhibitory capacities are known to rise and fall across the lifespan, we predicted that people's deductive reasoning performance would show similar curvilinear age trends. A group of children…

  15. The phytochemical glaucarubinone promotes mitochondrial metabolism, reduces body fat, and extends lifespan of Caenorhabditis elegans.

    Science.gov (United States)

    Zarse, K; Bossecker, A; Müller-Kuhrt, L; Siems, K; Hernandez, M A; Berendsohn, W G; Birringer, M; Ristow, M

    2011-04-01

    Naturally occurring compounds that promote energy expenditure and delay aging in model organisms may be of significant interest, since these substances potentially provide pharmaceutical approaches to tackle obesity and promote healthy lifespan in humans. We aimed to test whether pharmaceutical concentrations of glaucarubinone, a cytotoxic and antimalarial quassinoid known from different species of the plant family Simaroubaceae, are capable of affecting metabolism and/or extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Adult C. elegans roundworms, maintained on agar plates, were fed with E. coli strain OP50 bacteria, and glaucarubinone was applied to the agar to test (i) whether it alters respiration rates and mitochondrial activity, (ii) whether it affects body fat content, and (iii) whether it may promote longevity by quantifying survival in the presence and absence of the compound. We have found that glaucarubinone induces oxygen consumption and reduces body fat content of C. elegans. Moreover and consistent with the concept of mitohormesis, glaucarubinone extends C. elegans lifespan when applied at a concentration of 1 or 10 nanomolar. Taken together, glaucarubinone is capable of reducing body fat and promoting longevity in C. elegans, tentatively suggesting that this compound may promote metabolic health and lifespan in mammals and possibly humans.

  16. Calorie restriction does not elicit a robust extension of replicative lifespan in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Huberts, Daphne H.E.W.; Gonzalez Hernandez, Javier; Lee, Sung Sik; Litsios, Athanasios; Hubmann, Georg; Wit, Ernst C.; Heinemann, Matthias

    2014-01-01

    Calorie restriction (CR) is often described as the most robust manner to extend lifespan in a large variety of organisms. Hence, considerable research effort is directed toward understanding the mechanisms underlying CR, especially in the yeast Saccharomyces cerevisiae. However, the effect of CR on

  17. Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.

    Directory of Open Access Journals (Sweden)

    Laurent Kappeler

    2008-10-01

    Full Text Available Mutations that decrease insulin-like growth factor (IGF and growth hormone signaling limit body size and prolong lifespan in mice. In vertebrates, these somatotropic hormones are controlled by the neuroendocrine brain. Hormone-like regulations discovered in nematodes and flies suggest that IGF signals in the nervous system can determine lifespan, but it is unknown whether this applies to higher organisms. Using conditional mutagenesis in the mouse, we show that brain IGF receptors (IGF-1R efficiently regulate somatotropic development. Partial inactivation of IGF-1R in the embryonic brain selectively inhibited GH and IGF-I pathways after birth. This caused growth retardation, smaller adult size, and metabolic alterations, and led to delayed mortality and longer mean lifespan. Thus, early changes in neuroendocrine development can durably modify the life trajectory in mammals. The underlying mechanism appears to be an adaptive plasticity of somatotropic functions allowing individuals to decelerate growth and preserve resources, and thereby improve fitness in challenging environments. Our results also suggest that tonic somatotropic signaling entails the risk of shortened lifespan.

  18. Mental Illness and Mental Health: The Two Continua Model Across the Lifespan

    NARCIS (Netherlands)

    Westerhof, Gerben J.; Keyes, Cory L.M.

    2010-01-01

    Mental health has long been defined as the absence of psychopathologies, such as depression and anxiety. The absence of mental illness, however, is a minimal outcome from a psychological perspective on lifespan development. This article therefore focuses on mental illness as well as on three core co

  19. Cold storage affects mortality, body mass, lifespan, reproduction and flight capacity of Praon volucre (Hymenoptera: Braconidae)

    NARCIS (Netherlands)

    Lins, J.C.; Bueno, V.H.P.; Sidney, L.A.; Silva, D.B.; Sampaio, M.V.; Pereira, J.M.; Nomelini, Q.S.S.; Lenteren, van J.C.

    2013-01-01

    The possibility of storing natural enemies at low temperatures is important for the mass production of biological control agents. We evaluated the effect of different periods of cold storage on immature mortality, mummy body mass, lifespan, reproduction and flight capacity of the parasitoid Praon vo

  20. Growth hormone signaling is necessary for lifespan extension by dietary methionine.

    Science.gov (United States)

    Brown-Borg, Holly M; Rakoczy, Sharlene G; Wonderlich, Joseph A; Rojanathammanee, Lalida; Kopchick, John J; Armstrong, Vanessa; Raasakka, Debbie

    2014-12-01

    Growth hormone significantly impacts lifespan in mammals. Mouse longevity is extended when growth hormone (GH) signaling is interrupted but markedly shortened with high-plasma hormone levels. Methionine metabolism is enhanced in growth hormone deficiency, for example, in the Ames dwarf, but suppressed in GH transgenic mice. Methionine intake affects also lifespan, and thus, GH mutant mice and respective wild-type littermates were fed 0.16%, 0.43%, or 1.3% methionine to evaluate the interaction between hormone status and methionine. All wild-type and GH transgenic mice lived longer when fed 0.16% methionine but not when fed higher levels. In contrast, animals without growth hormone signaling due to hormone deficiency or resistance did not respond to altered levels of methionine in terms of lifespan, body weight, or food consumption. Taken together, our results suggest that the presence of growth hormone is necessary to sense dietary methionine changes, thus strongly linking growth and lifespan to amino acid availability.

  1. Whole lifespan microscopic observation of budding yeast aging through a microfluidic dissection platform

    NARCIS (Netherlands)

    Lee, Sung Sik; Avalos Vizcarra, Ima; Huberts, Daphne H E W; Lee, Luke P; Heinemann, Matthias

    2012-01-01

    Important insights into aging have been generated with the genetically tractable and short-lived budding yeast. However, it is still impossible today to continuously track cells by high-resolution microscopic imaging (e.g., fluorescent imaging) throughout their entire lifespan. Instead, the field st

  2. Genetic and Environmental Stability in Attention Problems across the Lifespan: Evidence from the Netherlands Twin Register

    Science.gov (United States)

    Kan, Kees-Jan; Dolan, Conor V.; Nivard, Michel G.; Middeldorp, Christel M.; van Beijsterveldt, Catharina E. M.; Willemsen, Gonneke; Boomsma, Dorret I.

    2013-01-01

    Objective: To review findings on attention-deficit/hyperactivity disorder and attention problems (AP) in children, adolescents, and adults, as established in the database of the Netherlands Twin Register and increase the understanding of stability in AP across the lifespan as a function of genetic and environmental influences. Method: A…

  3. Searching for a Life-Span Psychobiology of Down Syndrome: Advancing Educational and Behavioural Management Strategies.

    Science.gov (United States)

    Gibson, David

    1991-01-01

    Recent experimental research is synthesized to identify distinctive biobehavioral characteristics of Down's Syndrome persons across their lifespan. It is argued that educational and other intervention programs have not demonstrated strong gains having significant durability or generalization. Recommended is an interactionist function-structure…

  4. Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

    2015-12-25

    Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms.

  5. Epigenetic Effects of Diet on Fruit Fly Lifespan: An Investigation to Teach Epigenetics to Biology Students

    Science.gov (United States)

    Billingsley, James; Carlson, Kimberly A.

    2010-01-01

    Do our genes exclusively control us, or are other factors at play? Epigenetics can provide a means for students to use inquiry-based methods to understand a complex biological concept. Students research and design an experiment testing whether dietary supplements affect the lifespan of Drosophila melanogaster over multiple generations.

  6. Lifespan divergence between social insect castes : Challenges and opportunities for evolutionary theories of aging

    NARCIS (Netherlands)

    Kramer, Boris H; van Doorn, G Sander; Weissing, Franz J; Pen, Ido

    The extraordinarily long lifespans of queens (and kings) in eusocial insects and the strikingly large differences in life expectancy between workers and queens challenge our understanding of the evolution of aging and provide unique opportunities for studying the causes underlying adaptive variation

  7. Lifespan Aging and Belief Reasoning: Influences of Executive Function and Social Cue Decoding

    Science.gov (United States)

    Phillips, Louise H.; Bull, Rebecca; Allen, Roy; Insch, Pauline; Burr, Kirsty; Ogg, Will

    2011-01-01

    Older adults often perform poorly on Theory of Mind (ToM) tests that require understanding of others' beliefs and intentions. The course and specificity of age changes in belief reasoning across the adult lifespan is unclear, as is the cause of the age effects. Cognitive and neuropsychological models predict that two types of processing might…

  8. Epigallocatechin gallate affects glucose metabolism and increases fitness and lifespan in Drosophila melanogaster.

    Science.gov (United States)

    Wagner, Anika E; Piegholdt, Stefanie; Rabe, Doerte; Baenas, Nieves; Schloesser, Anke; Eggersdorfer, Manfred; Stocker, Achim; Rimbach, Gerald

    2015-10-13

    In this study, we tested whether a standardized epigallocatechin-3-gallate (EGCG) rich green tea extract (comprising > 90% EGCG) affects fitness and lifespan as well as parameters of glucose metabolism and energy homeostasis in the fruit fly, Drosophila melanogaster. Following the application of the green tea extract a significant increase in the mean lifespan (+ 3.3 days) and the 50% survival (+ 4.3 days) as well as improved fitness was detected. These effects went along an increased expression of Spargel, the homolog of mammalian PGC1α, which has been reported to affect lifespan in flies. Intriguingly, in flies, treatment with the green tea extract decreased glucose concentrations, which were accompanied by an inhibition of α-amylase and α-glucosidase activity. Computational docking analysis proved the potential of EGCG to dock into the substrate binding pocket of α-amylase and to a greater extent into α-glucosidase. Furthermore, we demonstrate that EGCG downregulates insulin-like peptide 5 and phosphoenolpyruvate carboxykinase, major regulators of glucose metabolism, as well as the Drosophila homolog of leptin, unpaired 2. We propose that a decrease in glucose metabolism in connection with an upregulated expression of Spargel contribute to the better fitness and the extended lifespan in EGCG-treated flies.

  9. Mental health and illness in relation to physical health across the lifespan

    NARCIS (Netherlands)

    Lamers, S.M.A.; Westerhof, Gerben Johan; Bohlmeijer, Ernst Thomas; Keyes, Corey L.M.; Sinnott, J.D.

    2013-01-01

    This chapter addresses mental health as more than the absence of disease, also approaching it from a positive perspective as the presence of well-being across the lifespan. The study described in the chapter investigated the association of age with psychopathology and positive mental health, control

  10. Differences in Binding and Monitoring Mechanisms Contribute to Lifespan Age Differences in False Memory

    Science.gov (United States)

    Fandakova, Yana; Shing, Yee Lee; Lindenberger, Ulman

    2013-01-01

    Based on a 2-component framework of episodic memory development across the lifespan (Shing & Lindenberger, 2011), we examined the contribution of memory-related binding and monitoring processes to false memory susceptibility in childhood and old age. We administered a repeated continuous recognition task to children (N = 20, 10-12 years),…

  11. Dance Talent Development across the Lifespan: A Review of Current Research

    Science.gov (United States)

    Chua, Joey

    2014-01-01

    The aim of this study is to compile and synthesize empirically based articles published between 2000 and 2012 about the critical issues of developing dance talents across the lifespan of children, adolescents and adults. The present article updates and extends a review article related to the identification and development in dance written by…

  12. Cold storage affects mortality, body mass, lifespan, reproduction and flight capacity of Praon volucre (Hymenoptera: Braconidae)

    NARCIS (Netherlands)

    Lins, J.C.; Bueno, V.H.P.; Sidney, L.A.; Silva, D.B.; Sampaio, M.V.; Pereira, J.M.; Nomelini, Q.S.S.; Lenteren, van J.C.

    2013-01-01

    The possibility of storing natural enemies at low temperatures is important for the mass production of biological control agents. We evaluated the effect of different periods of cold storage on immature mortality, mummy body mass, lifespan, reproduction and flight capacity of the parasitoid Praon

  13. Career Adaptability: An Integrative Construct for Life-Span, Life-Space Theory.

    Science.gov (United States)

    Savickas, Mark L.

    1997-01-01

    Examines the origin and current status of lifespan, life-space theory and proposes one way in which to integrate its three segments. Discusses a functionalist strategy for theory construction and the outcomes and consequences of this strategy. Discusses future directions for theory development, such as career adaptability and planful attitudes.…

  14. NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair

    DEFF Research Database (Denmark)

    Fang, Evandro Fei; Kassahun, Henok; Croteau, Deborah L

    2016-01-01

    function, delay memory loss, and extend lifespan in both animal models. Mechanistically, treatments that increase intracellular NAD(+) also stimulate neuronal DNA repair and improve mitochondrial quality via mitophagy. This work links two major theories on aging, DNA damage accumulation, and mitochondrial...

  15. PACRG, a protein linked to ciliary motility, mediates cellular signaling.

    Science.gov (United States)

    Loucks, Catrina M; Bialas, Nathan J; Dekkers, Martijn P J; Walker, Denise S; Grundy, Laura J; Li, Chunmei; Inglis, P Nick; Kida, Katarzyna; Schafer, William R; Blacque, Oliver E; Jansen, Gert; Leroux, Michel R

    2016-07-01

    Cilia are microtubule-based organelles that project from nearly all mammalian cell types. Motile cilia generate fluid flow, whereas nonmotile (primary) cilia are required for sensory physiology and modulate various signal transduction pathways. Here we investigate the nonmotile ciliary signaling roles of parkin coregulated gene (PACRG), a protein linked to ciliary motility. PACRG is associated with the protofilament ribbon, a structure believed to dictate the regular arrangement of motility-associated ciliary components. Roles for protofilament ribbon-associated proteins in nonmotile cilia and cellular signaling have not been investigated. We show that PACRG localizes to a small subset of nonmotile cilia in Caenorhabditis elegans, suggesting an evolutionary adaptation for mediating specific sensory/signaling functions. We find that it influences a learning behavior known as gustatory plasticity, in which it is functionally coupled to heterotrimeric G-protein signaling. We also demonstrate that PACRG promotes longevity in C. elegans by acting upstream of the lifespan-promoting FOXO transcription factor DAF-16 and likely upstream of insulin/IGF signaling. Our findings establish previously unrecognized sensory/signaling functions for PACRG and point to a role for this protein in promoting longevity. Furthermore, our work suggests additional ciliary motility-signaling connections, since EFHC1 (EF-hand containing 1), a potential PACRG interaction partner similarly associated with the protofilament ribbon and ciliary motility, also positively regulates lifespan.

  16. Lifespan-extending effects of royal jelly and its related substances on the nematode Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Yoko Honda

    Full Text Available BACKGROUND: One of the most important challenges in the study of aging is to discover compounds with longevity-promoting activities and to unravel their underlying mechanisms. Royal jelly (RJ has been reported to possess diverse beneficial properties. Furthermore, protease-treated RJ (pRJ has additional pharmacological activities. Exactly how RJ and pRJ exert these effects and which of their components are responsible for these effects are largely unknown. The evolutionarily conserved mechanisms that control longevity have been indicated. The purpose of the present study was to determine whether RJ and its related substances exert a lifespan-extending function in the nematode Caenorhabditis elegans and to gain insights into the active agents in RJ and their mechanism of action. PRINCIPAL FINDINGS: We found that both RJ and pRJ extended the lifespan of C. elegans. The lifespan-extending activity of pRJ was enhanced by Octadecyl-silica column chromatography (pRJ-Fraction 5. pRJ-Fr.5 increased the animals' lifespan in part by acting through the FOXO transcription factor DAF-16, the activation of which is known to promote longevity in C. elegans by reducing insulin/IGF-1 signaling (IIS. pRJ-Fr.5 reduced the expression of ins-9, one of the insulin-like peptide genes. Moreover, pRJ-Fr.5 and reduced IIS shared some common features in terms of their effects on gene expression, such as the up-regulation of dod-3 and the down-regulation of dod-19, dao-4 and fkb-4. 10-Hydroxy-2-decenoic acid (10-HDA, which was present at high concentrations in pRJ-Fr.5, increased lifespan independently of DAF-16 activity. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that RJ and its related substances extend lifespan in C. elegans, suggesting that RJ may contain longevity-promoting factors. Further analysis and characterization of the lifespan-extending agents in RJ and pRJ may broaden our understanding of the gene network involved in longevity regulation in diverse

  17. The Insulation for Machines Having a High Lifespan Expectancy, Design, Tests and Acceptance Criteria Issues

    Directory of Open Access Journals (Sweden)

    Olivier Barré

    2017-02-01

    Full Text Available The windings insulation of electrical machines will remain a topic that is updated frequently. The criteria severity requested by the electrical machine applications increases continuously. Manufacturers and designers are always confronted with new requirements or new criteria with enhanced performances. The most problematic requirements that will be investigated here are the extremely long lifespan coupled to critical operating conditions (overload, supply grid instabilities, and critical operating environments. Increasing lifespan does not have a considerable benefit because the purchasing price of usual machines has to be compared to the purchasing price and maintenance price of long lifespan machines. A machine having a 40-year lifespan will cost more than twice the usual price of a 20-year lifetime machine. Systems which need a long lifetime are systems which are crucial for a country, and those for which outage costs are exorbitant. Nuclear power stations are such systems. It is certain that the used technologies have evolved since the first nuclear power plant, but they cannot evolve as quickly as in other sectors of activities. No-one wants to use an immature technology in such power plants. Even if the electrical machines have exceeded 100 years of age, their improvements are linked to a patient and continuous work. Nowadays, the windings insulation systems have a well-established structure, especially high voltage windings. Unfortunately, a high life span is not only linked to this result. Several manufacturers’ improvements induced by many years of experiment have led to the writing of standards that help the customers and the manufacturers to regularly enhance the insulation specifications or qualifications. Hence, in this publication, the authors will give a step by step exhaustive review of one insulation layout and will take time to give a detailed report on the standards that are linked to insulation systems. No standard can

  18. Bacterial Respiration and Growth Rates Affect the Feeding Preferences, Brood Size and Lifespan of Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Li Yu

    Full Text Available Bacteria serve as live food and nutrients for bacterial-feeding nematodes (BFNs in soils, and influence nematodes behavior and physiology through their metabolism. Five bacterial taxa (Bacillus amyloliquefaciens JX1, Variovorax sp. JX14, Bacillus megaterium JX15, Pseudomonas fluorescens Y1 and Escherichia coli OP50 and the typical BFN Caenorhabditis elegans were selected to study the effects of bacterial respiration and growth rates on the feeding preferences, brood size and lifespan of nematodes. P. fluorescens Y1 and E. coli OP50 were found to be more active, with high respiration and rapid growth, whereas B. amyloliquefaciens JX1 and B. megaterium JX15 were inactive. The nematode C. elegans preferred active P. fluorescens Y1 and E. coli OP50 obviously. Furthermore, worms that fed on these two active bacteria produced more offspring but had shorter lifespan, while inactive and less preferred bacteria had increased nematodes lifespan and decreased the brood size. Based on these results, we propose that the bacterial activity may influence the behavior and life traits of C. elegans in the following ways: (1 active bacteria reproduce rapidly and emit high levels of CO2 attracting C. elegans; (2 these active bacteria use more resources in the nematodes' gut to sustain their survival and reproduction, thereby reducing the worm's lifespan; (3 inactive bacteria may provide less food for worms than active bacteria, thus increasing nematodes lifespan but decreasing their fertility. Nematodes generally require a balance between their preferred foods and beneficial foods, only preferred food may not be beneficial for nematodes.

  19. Bacterial Respiration and Growth Rates Affect the Feeding Preferences, Brood Size and Lifespan of Caenorhabditis elegans.

    Science.gov (United States)

    Yu, Li; Yan, Xiaomei; Ye, Chenglong; Zhao, Haiyan; Chen, Xiaoyun; Hu, Feng; Li, Huixin

    2015-01-01

    Bacteria serve as live food and nutrients for bacterial-feeding nematodes (BFNs) in soils, and influence nematodes behavior and physiology through their metabolism. Five bacterial taxa (Bacillus amyloliquefaciens JX1, Variovorax sp. JX14, Bacillus megaterium JX15, Pseudomonas fluorescens Y1 and Escherichia coli OP50) and the typical BFN Caenorhabditis elegans were selected to study the effects of bacterial respiration and growth rates on the feeding preferences, brood size and lifespan of nematodes. P. fluorescens Y1 and E. coli OP50 were found to be more active, with high respiration and rapid growth, whereas B. amyloliquefaciens JX1 and B. megaterium JX15 were inactive. The nematode C. elegans preferred active P. fluorescens Y1 and E. coli OP50 obviously. Furthermore, worms that fed on these two active bacteria produced more offspring but had shorter lifespan, while inactive and less preferred bacteria had increased nematodes lifespan and decreased the brood size. Based on these results, we propose that the bacterial activity may influence the behavior and life traits of C. elegans in the following ways: (1) active bacteria reproduce rapidly and emit high levels of CO2 attracting C. elegans; (2) these active bacteria use more resources in the nematodes' gut to sustain their survival and reproduction, thereby reducing the worm's lifespan; (3) inactive bacteria may provide less food for worms than active bacteria, thus increasing nematodes lifespan but decreasing their fertility. Nematodes generally require a balance between their preferred foods and beneficial foods, only preferred food may not be beneficial for nematodes.

  20. Validated Liquid Culture Monitoring System for Lifespan Extension of Caenorhabditis elegans through Genetic and Dietary Manipulations.

    Science.gov (United States)

    Win, Myat Thu Thu; Yamamoto, Yasuhiko; Munesue, Seiichi; Han, Dong; Harada, Shin-Ichi; Yamamoto, Hiroshi

    2013-08-01

    Nutritional and genetic factors influence aging and life expectancy. The reduction of food intake without malnutrition, referred to caloric restriction (CR), has been shown to increase lifespan in a wide variety of species. The nematode Caenorhabditis elegans (C. elegans) is one of the principle models with which to study the biology of aging and search for anti-aging compounds. In this study, we validated and optimized a high-throughput liquid culture system to monitor C. elegans lifespan with minimized mechanical stress. We used alive and ultraviolet (UV)-killed Escherichia coli (E. coli) OP50 at 10(8) or 10(9) colony-forming units (cfu)/ml to feed Bristol N2 wild-type (WT) and mutant worms of a well-characterized insulin/insulin-like growth factor signaling (ILS) pathway: the insulin receptor homolog daf-2 (e1370), phosphatidylinositol 3-kinase age-1 (hx546), and transcriptional factor FOXO homolog daf-16 (mu86 and mgDf50). Compared with alive E. coli at 10(9) cfu/ml, supplementations of alive E. coli at 10(8) cfu/ml or UV-killed E. coli at 10(9) cfu/ml dramatically prolonged lifespan in WT and age-1 mutants, and to a lesser extent, in daf-2 and daf-16 mutants, suggesting that signaling pathways in CR and ILS do not overlap fully. Feeding 10(8) cfu/ml UV-killed E. coli, which led to maximally saturated longevity in WT and daf-2 mutant, can prolonged lifespan in age-1, but not daf-16, mutants. This approach will be useful for investigating the biology of aging, physiological responses and gene functions under CR conditions and also for screening pharmacologic compounds to extend lifespan or affect other biologic processes.

  1. Trends in Life Expectancy and Lifespan Variation by Educational Attainment: United States, 1990-2010.

    Science.gov (United States)

    Sasson, Isaac

    2016-04-01

    The educational gradient in life expectancy is well documented in the United States and in other low-mortality countries. Highly educated Americans, on average, live longer than their low-educated counterparts, who have recently seen declines in adult life expectancy. However, limiting the discussion on lifespan inequality to mean differences alone overlooks other dimensions of inequality and particularly disparities in lifespan variation. The latter represents a unique form of inequality, with higher variation translating into greater uncertainty in the time of death from an individual standpoint, and higher group heterogeneity from a population perspective. Using data from the National Vital Statistics System from 1990 to 2010, this is the first study to document trends in both life expectancy and S25--the standard deviation of age at death above 25--by educational attainment. Among low-educated whites, adult life expectancy declined by 3.1 years for women and by 0.6 years for men. At the same time, S25 increased by about 1.5 years among high school-educated whites of both genders, becoming an increasingly important component of total lifespan inequality. By contrast, college-educated whites benefited from rising life expectancy and record low variation in age at death, consistent with the shifting mortality scenario. Among blacks, adult life expectancy increased, and S25 plateaued or declined in nearly all educational attainment groups, although blacks generally lagged behind whites of the same gender on both measures. Documenting trends in lifespan variation can therefore improve our understanding of lifespan inequality and point to diverging trajectories in adult mortality across socioeconomic strata.

  2. Low resting metabolic rate is associated with greater lifespan because of a confounding effect of body fatness.

    Science.gov (United States)

    Duarte, Luiza C; Speakman, John R

    2014-01-01

    A negative association between resting metabolic rate (RMR) and lifespan is the cornerstone of the rate of living and free-radical damage theories of aging. Empirical studies supporting a negative association of RMR to lifespan may arise from the correlation between RMR and both daily energy expenditure (DEE) and thermoregulatory activity energy expenditure (TAEE). We screened 540 female mice for higher and lower DEE and measured RMR in the resulting 324 (60 %). We then selected 92 mice in which there was no link between residual from the regression of RMR against body mass (BM) and residual of DEE against BM to separate the effects of these traits. Lifespan was not significantly related to body mass, DEE and TAEE, but significantly negatively related to RMR. Fat-free mass (FFM) and fat mass (FM) were both significantly positively related to RMR. After removing the effect of FFM on RMR, the association between RMR and lifespan remained significantly negative; however, after statistically removing the effect of FM on RMR, the significant association between RMR and lifespan disappeared. We conclude that the negative association between RMR and lifespan is primarily due to the effect of FM, with FM positively related to both RMR and mortality and hence RMR negatively to lifespan. In 40 additional screened mice, greater FM was also associated with greater oxidative damage to DNA.

  3. Trade-Offs between Growth Rate, Tree Size and Lifespan of Mountain Pine (Pinus montana) in the Swiss National Park.

    Science.gov (United States)

    Bigler, Christof

    2016-01-01

    A within-species trade-off between growth rates and lifespan has been observed across different taxa of trees, however, there is some uncertainty whether this trade-off also applies to shade-intolerant tree species. The main objective of this study was to investigate the relationships between radial growth, tree size and lifespan of shade-intolerant mountain pines. For 200 dead standing mountain pines (Pinus montana) located along gradients of aspect, slope steepness and elevation in the Swiss National Park, radial annual growth rates and lifespan were reconstructed. While early growth (i.e. mean tree-ring width over the first 50 years) correlated positively with diameter at the time of tree death, a negative correlation resulted with lifespan, i.e. rapidly growing mountain pines face a trade-off between reaching a large diameter at the cost of early tree death. Slowly growing mountain pines may reach a large diameter and a long lifespan, but risk to die young at a small size. Early growth was not correlated with temperature or precipitation over the growing period. Variability in lifespan was further contingent on aspect, slope steepness and elevation. The shade-intolerant mountain pines follow diverging growth trajectories that are imposed by extrinsic environmental influences. The resulting trade-offs between growth rate, tree size and lifespan advance our understanding of tree population dynamics, which may ultimately improve projections of forest dynamics under changing environmental conditions.

  4. Trade-Offs between Growth Rate, Tree Size and Lifespan of Mountain Pine (Pinus montana in the Swiss National Park.

    Directory of Open Access Journals (Sweden)

    Christof Bigler

    Full Text Available A within-species trade-off between growth rates and lifespan has been observed across different taxa of trees, however, there is some uncertainty whether this trade-off also applies to shade-intolerant tree species. The main objective of this study was to investigate the relationships between radial growth, tree size and lifespan of shade-intolerant mountain pines. For 200 dead standing mountain pines (Pinus montana located along gradients of aspect, slope steepness and elevation in the Swiss National Park, radial annual growth rates and lifespan were reconstructed. While early growth (i.e. mean tree-ring width over the first 50 years correlated positively with diameter at the time of tree death, a negative correlation resulted with lifespan, i.e. rapidly growing mountain pines face a trade-off between reaching a large diameter at the cost of early tree death. Slowly growing mountain pines may reach a large diameter and a long lifespan, but risk to die young at a small size. Early growth was not correlated with temperature or precipitation over the growing period. Variability in lifespan was further contingent on aspect, slope steepness and elevation. The shade-intolerant mountain pines follow diverging growth trajectories that are imposed by extrinsic environmental influences. The resulting trade-offs between growth rate, tree size and lifespan advance our understanding of tree population dynamics, which may ultimately improve projections of forest dynamics under changing environmental conditions.

  5. Embryonic expression of shuttle craft, a Drosophila gene involved in neuron development, is associated with adult lifespan.

    Science.gov (United States)

    Roshina, Natalia V; Symonenko, Alexander V; Krementsova, Anna V; Trostnikov, Mikhail V; Pasyukova, Elena G

    2014-12-01

    Despite the progress in aging research that highlights the role of the nervous system in longevity, whether genes that control development and consequently structure of the nervous system affect lifespan is unclear. We demonstrated that a mutation inshuttle craft, a gene involved in the nervous system development, increased the lifespan of unmated females and decreased the lifespan of mated females, without affecting males. Precise reversions of the mutation lead to the restoration of the lifespan specific to control females. In mutant unmated females, increased lifespan was associated with elevated locomotion at older ages, indicating slowed aging. In mutant mated females, reproduction was decreased compared to controls, indicating a lack of tradeoff between this trait and lifespan. No differences in shuttle craft transcription were observed between whole bodies, ovaries, and brains of mutant and control females of different ages, either unmated or mated. The amount of shuttle craft transcript appeared to be substantially decreased in mutant embryos. Our results demonstrated that a gene that regulates development of the nervous system might also influence longevity, and thus expanded the spectrum of genes involved in lifespan control. We hypothesize that this "carry-over" effect might be the result of transcription regulation in embryos.

  6. Architected Cellular Materials

    Science.gov (United States)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

    Additive manufacturing enables fabrication of materials with intricate cellular architecture, whereby progress in 3D printing techniques is increasing the possible configurations of voids and solids ad infinitum. Examples are microlattices with graded porosity and truss structures optimized for specific loading conditions. The cellular architecture determines the mechanical properties and density of these materials and can influence a wide range of other properties, e.g., acoustic, thermal, and biological properties. By combining optimized cellular architectures with high-performance metals and ceramics, several lightweight materials that exhibit strength and stiffness previously unachievable at low densities were recently demonstrated. This review introduces the field of architected materials; summarizes the most common fabrication methods, with an emphasis on additive manufacturing; and discusses recent progress in the development of architected materials. The review also discusses important applications, including lightweight structures, energy absorption, metamaterials, thermal management, and bioscaffolds.

  7. Epigenetics and Cellular Metabolism

    Science.gov (United States)

    Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well. PMID:27695375

  8. Cellular structural biology.

    Science.gov (United States)

    Ito, Yutaka; Selenko, Philipp

    2010-10-01

    While we appreciate the complexity of the intracellular environment as a general property of every living organism, we collectively lack the appropriate tools to analyze protein structures in a cellular context. In-cell NMR spectroscopy represents a novel biophysical tool to investigate the conformational and functional characteristics of biomolecules at the atomic level inside live cells. Here, we review recent in-cell NMR developments and provide an outlook towards future applications in prokaryotic and eukaryotic cells. We hope to thereby emphasize the usefulness of in-cell NMR techniques for cellular studies of complex biological processes and for structural analyses in native environments. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Cellular blue naevus

    Directory of Open Access Journals (Sweden)

    Mittal R

    2001-01-01

    Full Text Available A 31-year-old man had asymptomatic, stationary, 1.5X2 cm, shiny, smooth, dark blue nodule on dorsum of right hand since 12-14 years. In addition he had developed extensive eruption of yellow to orange papulonodular lesions on extensors of limbs and buttocks since one and half months. Investigations confirmed that yellow papules were xanthomatosis and he had associated diabetes mellitus and hyperlipidaemia. Biopsy of blue nodule confirmed the clinical diagnosis of cellular blue naevus. Cellular blue naevus is rare and its association with xanthomatosis and diabetes mellitus were interesting features of above patients which is being reported for its rarity.

  10. Lifespan extension and delay of age-related functional decline caused by Rhodiola rosea depends on dietary macronutrient balance

    Science.gov (United States)

    2013-01-01

    Background This study was conducted to evaluate the effects of rhizome powder from the herb Rhodiola rosea, a traditional Western Ukraine medicinal adaptogen, on lifespan and age-related physiological functions of the fruit fly Drosophila melanogaster. Results Flies fed food supplemented with 5.0 mg/ml and 10.0 mg/ml of R. rosea rhizome powder had a 14% to 17% higher median lifespan, whereas at 30.0 mg/ml lifespan was decreased by 9% to 12%. The preparation did not decrease fly fecundity. The effect of R. rosea supplement on lifespan was dependent on diet composition. Lifespan extension by 15% to 21% was observed only for diets with protein-to-carbohydrate ratios less than 1. Lifespan extension was also dependent on total concentration of macronutrients. Thus, for the diet with 15% yeast and 15% sucrose there was no lifespan extension, while for the diet with protein-to-carbohydrate ratio 20:1 R. rosea decreased lifespan by about 10%. Flies fed Rhodiola preparation were physically more active, less sensitive to the redox-cycling compound menadione and had a longer time of heat coma onset compared with controls. Positive effects of Rhodiola rhizome on stress resistance and locomotor activity were highest at the ‘middle age’. Conclusions The present data show that long-term food supplementation with R. rosea rhizome not only increases D. melanogaster lifespan, but also delays age-related decline of physical activity and increases stress resistance, what depends on protein-to-carbohydrate ratio of the diet. PMID:24472572

  11. Eugenia jambolana Lam. Increases lifespan and ameliorates experimentally induced neurodegeneration in C. elegans

    Directory of Open Access Journals (Sweden)

    Maria de Fátima Bezerra

    2014-09-01

    Full Text Available Summary. Type-2 diabetes mellitus (T2DM, dyslipidemia (DL and inflammation (IF are associated with reduced lifespan (LS and increased risk of neurodegenerative diseases (NDG. Dysregulation in insulin/insulin-like growth factor-1 (IGF-1 (IIS signaling, forkhead box O transcription factor (FOXO and Silent Information Regulators or Sirtuins (SIRT may be responsible. We investigated the effect of spray dried Jambolan (Eugenia jambolana Lam. fruit in Caenorhabditis elegans model for lifespan, amyloid b1-42 (Ab1-42 aggregation induced paralysis and MPP+ (1-methyl-4-phenylpyridinium induced neurodegeneration. Effect on modulating critical genes involved signaling pathways important in IIS, LS and NDG were also studied in C. elegans. Results show suggest statistically significant increase in lifespan (9-22.7% coupled with a delay in Ab1-42 induced paralysis (11.5% and MPP+ induced paralysis (38-43%. Gene expression studies indicated a significant upregulation in expression of  C. elegans homologs of foxo, sirt1, dopamine D1 receptor and suggested a non-FOXO mediated mechanism of action.Industrial relevance. Jambolan is a bioactive-rich tropical fruit with high colorant potential. Despite this fact, its perishability has hampered its market and industrial use beyond the countries where it is cultivated. Considering that drying is a popular technique able to extend fruits shelf life and concentrate their natural bioactive compounds, this research investigates the health relevance of spray dried jambolan. Here we addressed the potential of dried Jambolan fruit to extend lifespan and inhibit the progression of experimentally induced neurodegeneration using the C. elegans model. We demonstrated that this convenient fruit product was able to increase the lifespan of C. elegans. The jambolan extracts also influenced some critical genes of signaling pathways relevant to metabolic diseases, aging and neurodegeneration. Based on our results, some insight about

  12. Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans

    Science.gov (United States)

    Li, Yan-Hui; Zhang, Gai-Gai

    2016-01-01

    DAF-16, the C. elegans FOXO transcription factor, is an important determinant in aging and longevity. In this work, we manually curated FOXODB http://lyh.pkmu.cn/foxodb/, a database of FOXO direct targets. It now covers 208 genes. Bioinformatics analysis on 109 DAF-16 direct targets in C. elegans found interesting results. (i) DAF-16 and transcription factor PQM-1 co-regulate some targets. (ii) Seventeen targets directly regulate lifespan. (iii) Four targets are involved in lifespan extension induced by dietary restriction. And (iv) DAF-16 direct targets might play global roles in lifespan regulation. PMID:27027346

  13. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  14. Electromagnetic cellular interactions.

    Science.gov (United States)

    Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

    2011-05-01

    Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Cellular rehabilitation of photobiomodulation

    Science.gov (United States)

    Liu, Timon Cheng-Yi; Yuan, Jian-Qin; Wang, Yan-Fang; Xu, Xiao-Yang; Liu, Song-Hao

    2007-05-01

    Homeostasis is a term that refers to constancy in a system. A cell in homeostasis normally functions. There are two kinds of processes in the internal environment and external environment of a cell, the pathogenic processes (PP) which disrupts the old homeostasis (OH), and the sanogenetic processes (SP) which restores OH or establishes a new homeostasis (NH). Photobiomodualtion (PBM), the cell-specific effects of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems, is a kind of modulation on PP or SP so that there is no PBM on a cell in homeostasis. There are two kinds of pathways mediating PBM, the membrane endogenetic chromophores mediating pathways which often act through reactive oxygen species, and membrane proteins mediating pathways which often enhance cellular SP so that it might be called cellular rehabilitation. The cellular rehabilitation of PBM will be discussed in this paper. It is concluded that PBM might modulate the disruption of cellular homeostasis induced by pathogenic factors such as toxin until OH has been restored or NH has been established, but can not change homeostatic processes from one to another one.

  16. Cellular Response to Irradiation

    Institute of Scientific and Technical Information of China (English)

    LIU Bo; YAN Shi-Wei

    2011-01-01

    To explore the nonlinear activities of the cellular signaling system composed of one transcriptional arm and one protein-interaction arm, we use an irradiation-response module to study the dynamics of stochastic interactions.It is shown that the oscillatory behavior could be described in a unified way when the radiation-derived signal and noise are incorporated.

  17. Edible bird's nest enhances antioxidant capacity and increases lifespan in Drosophila Melanogaster.

    Science.gov (United States)

    Hu, Q; Li, G; Yao, H; He, S; Li, H; Liu, S; Wu, Y; Lai, X

    2016-04-30

    In this study, we aims to investigate the effects of edible bird's nest (EBN) on anti-aging efficacy. In order to investigate lifespan and mortality rate of flies, we treated flies with various doses of EBN. Besides, fecundity, water content and food are determined and heat-stress test is conducted after flies treating with different medium. Effects of EBN on total antioxidant activity (T-AOC), super-oxide dismutase activity (SOD), catalase activity (CAT), and malondialdehyde (MDA) were examined in drosophila melanogaster. Results indicated that flies in EBN treated group illustrated significantly lower mortality rates and longer median and maximum lifespan compared to control group (Pdrosophila melanogaster aging, attributing to the increasing antioxidant enzyme activities and decreasing content of lipid peroxidation products in drosophila melanogaster.

  18. The lifespan-promoting effect of acetic acid and Reishi polysaccharide.

    Science.gov (United States)

    Chuang, Ming-Hong; Chiou, Shyh-Horng; Huang, Chun-Hao; Yang, Wen-Bin; Wong, Chi-Huey

    2009-11-15

    Using Caenorhabditis elegans as a model organism, various natural substances and commercial health-food supplements were screened to evaluate their effects on longevity. Among the substances tested, acetic acid and Reishi polysaccharide fraction 3 (RF3) were shown to increase the expression of the lifespan and longevity-related transcription factor DAF-16 in C. elegans. We have shown that RF3 activates DAF-16 expression via TIR-1 receptor and MAPK pathway whereas acetic acid inhibits the trans-membrane receptor DAF-2 of the insulin/IGF-1 pathway to indirectly activate DAF-16 expression. In addition, a mixture of acetic acid and RF3 possesses a combined effect 30-40% greater than either substance used alone. A proteomic analysis of C. elegans using 2-DE and LC-MS/MS was then carried out, and 15 differentially expressed proteins involved in the lifespan-promoting activity were identified.

  19. Modeling of Self-Vibratory Drilling Head-Spindle System for Predictions of Bearings Lifespan

    Directory of Open Access Journals (Sweden)

    F. Forestier

    2011-01-01

    Full Text Available The machining of deep holes is limited due to inadequate chip evacuation, which induces tool breakage. To limit this drawback, retreat cycles and lubrication are used. An alternative response to the evacuation problem is based on high-speed vibratory drilling. A specific tool holder induces axial self-maintained vibration of the drill, which enables the chips to be split. The chips are thus of a small size and can be evacuated. To anticipate the potential risk of decreased spindle lifespan associated with these vibrations, a model of the behavior of the system (spindle—self-vibrating drilling head—tool is elaborated. In order to assess the dynamic behavior of the system, this study develops a rotor-based finite element model, integrated with the modelling of component interfaces. The current results indicate that the simulations are consistent with the experimental measurements. The influence of spindle speed and feed rate on bearing lifespan is highlighted.

  20. INFLUENCE OF AMYLOSE STARCH ON DEVELOPMENT AND LIFESPAN OF FRUIT FLY DROSOPHILA MELANOGASTER

    Directory of Open Access Journals (Sweden)

    Oleksandra Abrat

    2015-05-01

    Full Text Available Last years, the concept of resistant starch (RS has evoked a new interest in researchers in the context of bioavailability of starch and its use as a source of dietary fiber. Based on clinical and animal research, RS has been proposed to be the most potentially beneficial starch fraction for human health. In this study, the effects of amylose starch as a fraction of RS on development and lifespan of fruit fly Drosophila melanogaster were investigated. In both Canton S and w1118 strains, the diet with 20% amylose RS delayed fly development, increased triacylglyceride level in the body of adult insects and reduced their lifespan compared to the diet with 4% amylose starch. Thus, our data clearly demonstrate that amylose starch at high concentrations may negatively affect fruit fly.

  1. GDF11 administration does not extend lifespan in a mouse model of premature aging

    Science.gov (United States)

    Freitas-Rodríguez, Sandra; Rodríguez, Francisco; Folgueras, Alicia R.

    2016-01-01

    GDF11 has recently emerged as a powerful anti-aging candidate, found in young blood, capable of rejuvenating a number of aged tissues, such as heart, skeletal muscle and brain. However, recent reports have shown contradictory data questioning its capacity to reverse age-related tissue dysfunction. The availability of a mouse model of accelerated aging, which shares most of the features occurring in physiological aging, gives us an excellent opportunity to test in vivo therapies aimed at extending lifespan both in pathological and normal aging. On this basis, we wondered whether the proposed anti-aging functions of GDF11 would have an overall effect on longevity. We first confirmed the existence of a reduction in GDF11/8 levels in our mouse model of accelerated aging compared with wild-type littermates. However, we show herein that GDF11 daily administration does not extend lifespan of premature-aged mice. PMID:27507054

  2. [Reversal of aging and lifespan elongation. Current biomedical key publications and the implications for geriatrics].

    Science.gov (United States)

    Bollheimer, L C; Volkert, D; Bertsch, T; Sieber, C C; Büttner, R

    2013-08-01

    Biological aging means a time-dependent accumulation of changes to which a living organism is being exposed during its lifetime. Biological aging normally concurs with chronological aging the time frame of which is set by an upper limit, the lifespan (in humans approximately 120 years). New findings in experimental biogerontology are challenging both the dogma of irreversibility of biological aging and the preset species-specific limitations of life. The present overview first explains the general principle of rejuvenation and reversal of biological aging with paradigms from stem cell research. Secondly, recent key publications on artificial telomerase elongation and (alleged) lifespan enhancement by sirtuins and resveratrol will be discussed with an emphasis on the implications for (future) geriatric medicine.

  3. Subjective Well-being Across the Lifespan in Europe and Central Asia

    DEFF Research Database (Denmark)

    Bauer, Jan Michael; Levin, Victoria; Munoz Boudet, Ana Maria;

    2016-01-01

    controlling for socio-demographic characteristics, this pattern generally remains robust for most of our cross-sectional and panel analyses. Hence, despite significant heterogeneity in the pattern of well-being across the lifespan within the ECA region, we do not observe high levels of cross-country or cross......sing data from the Integrated Values Survey (IVS), the Life in Transition Survey (LiTS), and the Russia Longitudinal Monitoring Survey (RLMS), we analyse the relation between age and subjective well-being in the World Bank’s Europe and Central Asia (ECA) region and compare it to that in Western...... Europe. Although our results generally confirm previous studies’ findings of a U-shaped relation between subjective well-being and age for most of the lifecycle, we also find that well-being in ECA declines again after the 70s, giving rise to an S-shape relation across the entire lifespan. When...

  4. Preventing Age-Related Decline of Gut Compartmentalization Limits Microbiota Dysbiosis and Extends Lifespan.

    Science.gov (United States)

    Li, Hongjie; Qi, Yanyan; Jasper, Heinrich

    2016-02-10

    Compartmentalization of the gastrointestinal (GI) tract of metazoans is critical for health. GI compartments contain specific microbiota, and microbiota dysbiosis is associated with intestinal dysfunction. Dysbiosis develops in aging intestines, yet how this relates to changes in GI compartmentalization remains unclear. The Drosophila GI tract is an accessible model to address this question. Here we show that the stomach-like copper cell region (CCR) in the middle midgut controls distribution and composition of the microbiota. We find that chronic activation of JAK/Stat signaling in the aging gut induces a metaplasia of the gastric epithelium, CCR decline, and subsequent commensal dysbiosis and epithelial dysplasia along the GI tract. Accordingly, inhibition of JAK/Stat signaling in the CCR specifically prevents age-related metaplasia, commensal dysbiosis and functional decline in old guts, and extends lifespan. Our results establish a mechanism by which age-related chronic inflammation causes the decline of intestinal compartmentalization and microbiota dysbiosis, limiting lifespan.

  5. Subjective Well-being Across the Lifespan in Europe and Central Asia

    DEFF Research Database (Denmark)

    Bauer, Jan Michael; Levin, Victoria; Munoz Boudet, Ana Maria

    2016-01-01

    sing data from the Integrated Values Survey (IVS), the Life in Transition Survey (LiTS), and the Russia Longitudinal Monitoring Survey (RLMS), we analyse the relation between age and subjective well-being in the World Bank’s Europe and Central Asia (ECA) region and compare it to that in Western...... Europe. Although our results generally confirm previous studies’ findings of a U-shaped relation between subjective well-being and age for most of the lifecycle, we also find that well-being in ECA declines again after the 70s, giving rise to an S-shape relation across the entire lifespan. When...... controlling for socio-demographic characteristics, this pattern generally remains robust for most of our cross-sectional and panel analyses. Hence, despite significant heterogeneity in the pattern of well-being across the lifespan within the ECA region, we do not observe high levels of cross-country or cross...

  6. The gametic central cell of Arabidopsis determines the lifespan of adjacent accessory cells

    OpenAIRE

    Kägi, Christina; Baumann, Nadine; Nielsen, Nicola; Stierhof, York-Dieter; Groß-Hardt, Rita

    2010-01-01

    Plant germ cells develop in specialized haploid structures, termed gametophytes. The female gametophyte patterns of flowering plants are diverse, with often unknown adaptive value. Here we present the Arabidopsis fiona mutant, which forms a female gametophyte that is structurally and functionally reminiscent of a phylogenetic distant female gametophyte. The respective changes include a modified reproductive behavior of one of the female germ cells (central cell) and an extended lifespan of th...

  7. Mutation in E1, the ubiquitin activating enzyme, reduces Drosophila lifespan and results in motor impairment.

    Science.gov (United States)

    Liu, Hsiu-Yu; Pfleger, Cathie M

    2013-01-01

    Neurodegenerative diseases cause tremendous suffering for those afflicted and their families. Many of these diseases involve accumulation of mis-folded or aggregated proteins thought to play a causal role in disease pathology. Ubiquitinated proteins are often found in these protein aggregates, and the aggregates themselves have been shown to inhibit the activity of the proteasome. These and other alterations in the Ubiquitin Pathway observed in neurodegenerative diseases have led to the question of whether impairment of the Ubiquitin Pathway on its own can increase mortality or if ongoing neurodegeneration alters Ubiquitin Pathway function as a side-effect. To address the role of the Ubiquitin Pathway in vivo, we studied loss-of-function mutations in the Drosophila Ubiquitin Activating Enzyme, Uba1 or E1, the most upstream enzyme in the Ubiquitin Pathway. Loss of only one functional copy of E1 caused a significant reduction in adult lifespan. Rare homozygous hypomorphic E1 mutants reached adulthood. These mutants exhibited further reduced lifespan and showed inappropriate Ras activation in the brain. Removing just one functional copy of Ras restored the lifespan of heterozygous E1 mutants to that of wild-type flies and increased the survival of homozygous E1 mutants. E1 homozygous mutants also showed severe motor impairment. Our findings suggest that processes that impair the Ubiquitin Pathway are sufficient to cause early mortality. Reduced lifespan and motor impairment are seen in the human disease X-linked Infantile Spinal Muscular Atrophy, which is associated with mutation in human E1 warranting further analysis of these mutants as a potential animal model for study of this disease.

  8. Lifespan effects of simple and complex nutraceutical combinations fed isocalorically to mice

    OpenAIRE

    Spindler, Stephen R.; Mote, Patricia L.; Flegal, James M.

    2013-01-01

    Present data suggest that the consumption of individual dietary supplements does not enhance the health or longevity of healthy rodents or humans. It might be argued that more complex combinations of such agents might extend lifespan or health-span by more closely mimicking the complexity of micronutrients in fruits and vegetables, which appear to extend health-span and longevity. To test this hypothesis we treated long-lived, male, F1 mice with published and commercial combinations of dietar...

  9. Applying a Lifespan Developmental Perspective to Chronic Pain: Pediatrics to Geriatrics.

    Science.gov (United States)

    Walco, Gary A; Krane, Elliot J; Schmader, Kenneth E; Weiner, Debra K

    2016-09-01

    An ideal taxonomy of chronic pain would be applicable to people of all ages. Developmental sciences focus on lifespan developmental approaches, and view the trajectory of processes in the life course from birth to death. In this article we provide a review of lifespan developmental models, describe normal developmental processes that affect pain processing, and identify deviations from those processes that lead to stable individual differences of clinical interest, specifically the development of chronic pain syndromes. The goals of this review were 1) to unify what are currently separate purviews of "pediatric pain," "adult pain," and "geriatric pain," and 2) to generate models so that specific elements of the chronic pain taxonomy might include important developmental considerations. A lifespan developmental model is applied to the forthcoming Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks-American Pain Society Pain Taxonomy to ascertain the degree to which general "adult" descriptions apply to pediatric and geriatric populations, or if age- or development-related considerations need to be invoked. Copyright © 2016. Published by Elsevier Inc.

  10. Reorder Write Sequence by Hetero-Buffer to Extend SSD's Lifespan

    Institute of Scientific and Technical Information of China (English)

    Zhi-Guang Chen; Nong Xiao; Fang Liu; Yi-Mo Du

    2013-01-01

    The limited lifespan is the Achilles' heel of solid state drives (SSDs) based on NAND flash.NAND flash has two drawbacks that degrade SSDs' lifespan.One is the out-of-place update.Another is the sequential write constraint within a block.SSDs usually employ write buffer to extend their lifetime.However,existing write buffer schemes only pay attention to the first drawback,while neglect the second one.We propose a hetero-buffer architecture covering both aspects simultaneously.The hetero-buffer consists of two components,dynamic random access memory (DRAM) and the reorder area.DRAM endeavors to reduce write traffic as much as possible by pursuing a higher hit ratio (overcome the first drawback).The reorder area focuses on reordering write sequence (overcome the second drawback).Our hetero-buffer outperforms traditional write buffers because of two reasons.First,the DRAM can adopt existing superior cache replacement policy,thus achieves higher hit ratio.Second,the hetero-buffer reorders the write sequence,which has not been exploited by traditional write buffers.Besides the optimizations mentioned above,our hetero-buffer considers the work environment of write buffer,which is also neglected by traditional write buffers.By this way,the hetero-buffer is further improved.The performance is evaluated via trace-driven simulations.Experimental results show that,SSDs employing the hetero-buffer survive longer lifespan on most workloads.

  11. Heliogeophysical factors at time of death determine lifespan for people who die of cardiovascular diseases

    Science.gov (United States)

    Melnikov, Vladimir N.

    2010-09-01

    The aim of the study is to explore whether age at death from cardiovascular diseases depends on solar and geomagnetic activities. The data were collected for 1970-1978 in Novosibirsk, West Siberia, for industrial workers of Siberian origin. The Spearman correlations are computed between linearly detrended lifespan and daily or monthly physical variables to establish immediate (lag, L = 0), delayed ( L = 1-3 days) and cumulative ( L = ±30 days) influences. Significant correlations ranging from r = -0.26 to r = -0.30 for L from 0 to 3, respectively, are found for men between solar radio flux at wavelength 10.7 cm and age at death from acute myocardial infarction (AMI) but not from acute heart failure, ischemic heart disease and stroke. For AMI, women's longevity displays an opposite (direct) association with the average solar character occurred at the calendar month of death. The index of geomagnetic activity, Ap, exhibits inverse association with longevity for the AMI stratum for both sexes. GLM univariate procedure revealed higher contribution of Ap to the variance of lifespan compared to season of death. The individual age at death susceptibility to cosmic influences is found to depend upon solar activity at year of birth. It is concluded that associations between the lifespan for cardiovascular decedents and the indices of solar and geomagnetic activities at time of death and of birth are cause-of-death- and sex-specific.

  12. Effects of calorie restriction on the lifespan and healthspan of POLG mitochondrial mutator mice

    Science.gov (United States)

    Kim, Mi-Jung; Hacker, Timothy A.; Vermulst, Marc; Weindruch, Richard; Prolla, Tomas A.

    2017-01-01

    Mitochondrial DNA (mtDNA) mutations are thought to have a causative role in age-related pathologies. We have shown previously that mitochondrial mutator mice (PolgD257A/D257A), harboring a proofreading-deficient version of the mtDNA polymerase gamma (POLG), accumulate mtDNA mutations in multiple tissues and display several features of accelerated aging. Calorie restriction (CR) is known to delay the onset of age-related diseases and to extend the lifespan of a variety of species, including rodents. In the current study we investigated the effects of CR on the lifespan and healthspan of mitochondrial mutator mice. Long-term CR did not increase the median or maximum lifespan of PolgD257A/D257A mice. Furthermore, CR did not reduce mtDNA deletions in the heart and muscle, accelerated sarcopenia, testicular atrophy, nor improve the alterations in cardiac parameters that are present in aged mitochondrial mutator mice. Therefore, our findings suggest that accumulation of mtDNA mutations may interfere with the beneficial action of CR in aging retardation. PMID:28158260

  13. Entropy Generation and Human Aging: Lifespan Entropy and Effect of Physical Activity Level

    Science.gov (United States)

    Silva, Carlos; Annamalai, Kalyan

    2008-06-01

    The first and second laws of thermodynamics were applied to biochemical reactions typical of human metabolism. An open-system model was used for a human body. Energy conservation, availability and entropy balances were performed to obtain the entropy generated for the main food components. Quantitative results for entropy generation were obtained as a function of age using the databases from the U.S. Food and Nutrition Board (FNB) and Centers for Disease Control and Prevention (CDC), which provide energy requirements and food intake composition as a function of age, weight and stature. Numerical integration was performed through human lifespan for different levels of physical activity. Results were presented and analyzed. Entropy generated over the lifespan of average individuals (natural death) was found to be 11,404 kJ/ºK per kg of body mass with a rate of generation three times higher on infants than on the elderly. The entropy generated predicts a life span of 73.78 and 81.61 years for the average U.S. male and female individuals respectively, which are values that closely match the average lifespan from statistics (74.63 and 80.36 years). From the analysis of the effect of different activity levels, it is shown that entropy generated increases with physical activity, suggesting that exercise should be kept to a “healthy minimum” if entropy generation is to be minimized.

  14. Life-Span Differences in the Uses and Gratifications of Tablets: Implications for Older Adults.

    Science.gov (United States)

    Magsamen-Conrad, Kate; Dowd, John; Abuljadail, Mohammad; Alsulaiman, Saud; Shareefi, Adnan

    2015-11-01

    This study extends Uses and Gratifications theory by examining the uses and gratifications of a new technological device, the tablet computer, and investigating the differential uses and gratifications of tablet computers across the life-span. First, we utilized a six-week tablet training intervention to adapt and extend existing measures to the tablet as a technological device. Next, we used paper-based and online surveys (N=847), we confirmed four main uses of tablets: 1) Information Seeking, 2) Relationship Maintenance, 3) Style, 4) Amusement and Killing time, and added one additional use category 5) Organization. We discovered differences among the five main uses of tablets across the life-span, with older adults using tablets the least overall. Builders, Boomers, GenX and GenY all reported the highest means for information seeking. Finally, we used a structural equation model to examine how uses and gratifications predicts hours of tablet use. The study provides limitations and suggestions for future research and marketers. In particular, this study offers insight to the relevancy of theory as it applies to particular information and communication technologies and consideration of how different periods in the life-span affect tablet motivations.

  15. Hexokinase is a key regulator of energy metabolism and ROS activity in insect lifespan extension

    Science.gov (United States)

    Lin, Xian-Wu; Xu, Wei-Hua

    2016-01-01

    Developmental arrest (diapause) is a ‘non-aging’ state that is similar to the Caenorhabditis elegans dauer stage and Drosophila lifespan extension. Diapause results in low metabolic activity and a profound extension of insect lifespan. Here, we cloned the Helicoverpa armigera Hexokinase (HK) gene, a gene that is critical for the developmental arrest of this species. HK expression and activity levels were significantly increased in nondiapause-destined pupae compared with those of diapause-destined pupae. Downregulation of HK activity reduced cell viability and delayed pupal development by reducing metabolic activity and increasing ROS activity, which suggests that HK is a key regulator of insect development. We then identified the transcription factors Har-CREB, -c-Myc, and -POU as specifically binding the Har-HK promoter and regulating its activity. Intriguingly, Har-POU and -c-Myc are specific transcription factors for HK expression, whereas Har-CREB is nonspecific. Furthermore, Har-POU and -c-Myc could respond to ecdysone, which is an upstream hormone. Therefore, low ecdysone levels in diapause-destined individuals lead to low Har-POU and -c-Myc expression levels, ultimately repressing Har-HK expression and inducing entry into diapause or lifespan extension. PMID:26852422

  16. Reduction of mitoferrin results in abnormal development and extended lifespan in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Yaguang Ren

    Full Text Available Iron is essential for organisms. It is mainly utilized in mitochondria for biosynthesis of iron-sulfur clusters, hemes and other cofactors. Mitoferrin 1 and mitoferrin 2, two homologues proteins belonging to the mitochondrial solute carrier family, are required for iron delivery into mitochondria. Mitoferrin 1 is highly expressed in developing erythrocytes which consume a large amount of iron during hemoglobinization. Mitoferrin 2 is ubiquitously expressed, whose functions are less known. Zebrafish with mitoferrin 1 mutation show profound hypochromic anaemia and erythroid maturation arrests, and yeast with defects in MRS3/4, the counterparts of mitoferrin 1/2, has low mitochondrial iron levels and grows poorly by iron depletion. Mitoferrin 1 expression is up-regulated in yeast and mouse models of Fiedreich's ataxia disease and in human cell culture models of Parkinson disease, suggesting its involvement in the pathogenesis of diseases with mitochondrial iron accumulation. In this study we found that reduced mitoferrin levels in C. elegans by RNAi treatment causes pleiotropic phenotypes such as small body size, reduced fecundity, slow movement and increased sensitivity to paraquat. Despite these abnormities, lifespan was increased by 50% to 80% in N2 wild type strain, and in further studies using the RNAi sensitive strain eri-1, more than doubled lifespan was observed. The pathways or mechanisms responsible for the lifespan extension and other phenotypes of mitoferrin RNAi worms are worth further study, which may contribute to our understanding of aging mechanisms and the pathogenesis of iron disorder related diseases.

  17. Mitochondrial Inverted Repeats Strongly Correlate with Lifespan: mtDNA Inversions and Aging

    Science.gov (United States)

    Yang, Jiang-Nan; Seluanov, Andrei; Gorbunova, Vera

    2013-01-01

    Mitochondrial defects are implicated in aging and in a multitude of age-related diseases, such as cancer, heart failure, Parkinson’s disease, and Huntington’s disease. However, it is still unclear how mitochondrial defects arise under normal physiological conditions. Mitochondrial DNA (mtDNA) deletions caused by direct repeats (DRs) are implicated in the formation of mitochondrial defects, however, mitochondrial DRs show relatively weak (Pearson’s r = −0.22, p<0.002; Spearman’s ρ = −0.12, p = 0.1) correlation with maximum lifespan (MLS). Here we report a stronger correlation (Pearson’s r = −0.55, p<10–16; Spearman’s ρ = −0.52, p<10–14) between mitochondrial inverted repeats (IRs) and lifespan across 202 species of mammals. We show that, in wild type mice under normal conditions, IRs cause inversions, which arise by replication-dependent mechanism. The inversions accumulate with age in the brain and heart. Our data suggest that IR-mediated inversions are more mutagenic than DR-mediated deletions in mtDNA, and impose stronger constraint on lifespan. Our study identifies IR-induced mitochondrial genome instability during mtDNA replication as a potential cause for mitochondrial defects. PMID:24069185

  18. Mitochondrial inverted repeats strongly correlate with lifespan: mtDNA inversions and aging.

    Directory of Open Access Journals (Sweden)

    Jiang-Nan Yang

    Full Text Available Mitochondrial defects are implicated in aging and in a multitude of age-related diseases, such as cancer, heart failure, Parkinson's disease, and Huntington's disease. However, it is still unclear how mitochondrial defects arise under normal physiological conditions. Mitochondrial DNA (mtDNA deletions caused by direct repeats (DRs are implicated in the formation of mitochondrial defects, however, mitochondrial DRs show relatively weak (Pearson's r = -0.22, p<0.002; Spearman's ρ = -0.12, p = 0.1 correlation with maximum lifespan (MLS. Here we report a stronger correlation (Pearson's r = -0.55, p<10(-16; Spearman's ρ = -0.52, p<10(-14 between mitochondrial inverted repeats (IRs and lifespan across 202 species of mammals. We show that, in wild type mice under normal conditions, IRs cause inversions, which arise by replication-dependent mechanism. The inversions accumulate with age in the brain and heart. Our data suggest that IR-mediated inversions are more mutagenic than DR-mediated deletions in mtDNA, and impose stronger constraint on lifespan. Our study identifies IR-induced mitochondrial genome instability during mtDNA replication as a potential cause for mitochondrial defects.

  19. Caenorhabditis elegans Genes Affecting Interindividual Variation in Life-span Biomarker Gene Expression.

    Science.gov (United States)

    Mendenhall, Alexander; Crane, Matthew M; Tedesco, Patricia M; Johnson, Thomas E; Brent, Roger

    2017-10-01

    Genetically identical organisms grown in homogenous environments differ in quantitative phenotypes. Differences in one such trait, expression of a single biomarker gene, can identify isogenic cells or organisms that later manifest different fates. For example, in isogenic populations of young adult Caenorhabditis elegans, differences in Green Fluorescent Protein (GFP) expressed from the hsp-16.2 promoter predict differences in life span. Thus, it is of interest to determine how interindividual differences in biomarker gene expression arise. Prior reports showed that the thermosensory neurons and insulin signaling systems controlled the magnitude of the heat shock response, including absolute expression of hsp-16.2. Here, we tested whether these regulatory signals might also influence variation in hsp-16.2 reporter expression. Genetic experiments showed that the action of AFD thermosensory neurons increases interindividual variation in biomarker expression. Further genetic experimentation showed the insulin signaling system acts to decrease interindividual variation in life-span biomarker expression; in other words, insulin signaling canalizes expression of the hsp-16.2-driven life-span biomarker. Our results show that specific signaling systems regulate not only expression level, but also the amount of interindividual expression variation for a life-span biomarker gene. They raise the possibility that manipulation of these systems might offer means to reduce heterogeneity in the aging process. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Methuselah-like genes affect development, stress resistance, lifespan and reproduction in Tribolium castaneum.

    Science.gov (United States)

    Li, Chengjun; Zhang, Yi; Yun, Xiaopei; Wang, Yanyun; Sang, Ming; Liu, Xing; Hu, Xingxing; Li, Bin

    2014-10-01

    Methuselah (Mth) is associated with lifespan, stress resistance and reproduction in Drosophila melanogaster, but Mth is not present in nondrosophiline insects. A number of methuselah-likes (mthls) have been identified in nondrosophiline insects, but it is unknown whether the functions of mth are shared by mthls or are divergent from them. Five mthls have been identified in Tribolium castaneum. Although they have different developmental expression patterns, they all enhance resistance to starvation. Only mthl1 and mthl2 enhance resistance to high temperature, whereas mthl4 and mthl5 negatively regulate oxidative stress in T. castaneum. Unlike in the fly with mth mutation, knockdown of mthls, except mthl3, shortens the lifespan of T. castaneum. Moreover, mthl1 and mthl2 are critical for Tribolium development. mthl1 plays important roles in larval and pupal development and adult eclosion, while mthl2 is required for eclosion. Moreover, mthl1 and mthl2 silencing reduces the fertility of T. castaneum, and mthl1 and mthl4 are also essential for embryo development. In conclusion, mthls have a significant effect on insect development, lifespan, stress resistance and reproduction. These results provide experimental evidence for functional divergence among mthls/mth and clues for the signal transduction of Mthls.

  1. Reduction of mitoferrin results in abnormal development and extended lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Ren, Yaguang; Yang, Su; Tan, Guoqiang; Ye, Wei; Liu, Danhui; Qian, Xu; Ding, Zhongying; Zhong, Yuhong; Zhang, Jingrui; Jiang, Dandan; Zhao, Yuhong; Lu, Jianxin

    2012-01-01

    Iron is essential for organisms. It is mainly utilized in mitochondria for biosynthesis of iron-sulfur clusters, hemes and other cofactors. Mitoferrin 1 and mitoferrin 2, two homologues proteins belonging to the mitochondrial solute carrier family, are required for iron delivery into mitochondria. Mitoferrin 1 is highly expressed in developing erythrocytes which consume a large amount of iron during hemoglobinization. Mitoferrin 2 is ubiquitously expressed, whose functions are less known. Zebrafish with mitoferrin 1 mutation show profound hypochromic anaemia and erythroid maturation arrests, and yeast with defects in MRS3/4, the counterparts of mitoferrin 1/2, has low mitochondrial iron levels and grows poorly by iron depletion. Mitoferrin 1 expression is up-regulated in yeast and mouse models of Fiedreich's ataxia disease and in human cell culture models of Parkinson disease, suggesting its involvement in the pathogenesis of diseases with mitochondrial iron accumulation. In this study we found that reduced mitoferrin levels in C. elegans by RNAi treatment causes pleiotropic phenotypes such as small body size, reduced fecundity, slow movement and increased sensitivity to paraquat. Despite these abnormities, lifespan was increased by 50% to 80% in N2 wild type strain, and in further studies using the RNAi sensitive strain eri-1, more than doubled lifespan was observed. The pathways or mechanisms responsible for the lifespan extension and other phenotypes of mitoferrin RNAi worms are worth further study, which may contribute to our understanding of aging mechanisms and the pathogenesis of iron disorder related diseases.

  2. The First International Mini-Symposium on Methionine Restriction and Lifespan

    Directory of Open Access Journals (Sweden)

    Gene eAbles

    2014-05-01

    Full Text Available It has been 20 years since the Orentreich Foundation for the Advancement of Science, under the leadership Dr. Norman Orentreich, first reported that low methionine (Met ingestion by rats extends lifespan [1]. Since then, several studies have replicated the effects of dietary methionine restriction (MR in delaying age-related diseases [2–5]. We report the abstracts from the First International Mini-Symposium on Methionine Restriction and Lifespan held in Tarrytown, NY last September 2013. The goals were 1 to gather researchers with an interest in methionine restriction and lifespan, 2 to exchange knowledge, 3 to generate ideas for future investigations, and 4 to strengthen relationships within this community. The presentations highlighted the importance of research on cysteine, growth hormone (GH, and ATF4 in the paradigm of aging. In addition, the effects of dietary restriction or MR in the kidneys, liver, bones and the adipose tissue were discussed. The symposium also emphasized the value of other species, e.g. the naked mole rat, Brandt’s bat and drosophila in aging research. Overall, the symposium consolidated scientists with similar research interests and provided opportunities to conduct future collaborative studies.

  3. Implications of Methodist clergies’ average lifespan and missional lessons learned from obituaries of deceased ministers

    Directory of Open Access Journals (Sweden)

    Lehlohonolo J. Mathibe

    2015-03-01

    Full Text Available We are born, we touch the lives of others, we die – and then we are remembered. For the purpose of this article, I have assessed from obituaries the average lifespan of the clergy (ministers in the Methodist Church of South Africa (MCSA, who died between 2003 and 2014. These obituaries were published in the Yearbooks of the MCSA from 2004 to 2015. I also give attention to how the deceased ministers are remembered. The average lifespan of Methodist ministers is 72 years, and it is likely to increase to 74 years by 2023. This article discusses the implications of Methodist ministers’ average lifespan and suggests that the clergy should be encouraged and enabled to retire at the age of 60 years. The following 12 themes (or missional lessons, mainly answering the question of how the clergy are remembered, emerged from the qualitative analysis of obituaries: they were gifted preachers of the gospel of Jesus Christ; they lived a balanced life; they were humble servants in Jesus’ vineyard; they were sensitive storytellers with a deep sense of humour; they were community builders; they were leaders and meticulous in administration; they were prayer warriors; they loved and valued education; they were disciplined and principled; they enjoyed music; they worked hard for an everlasting peace on earth; and they were zealous stewards of God’s creation.

  4. Genetic Manipulation of Glycogen Allocation Affects Replicative Lifespan in E. coli.

    Science.gov (United States)

    Boehm, Alex; Arnoldini, Markus; Bergmiller, Tobias; Röösli, Thomas; Bigosch, Colette; Ackermann, Martin

    2016-04-01

    In bacteria, replicative aging manifests as a difference in growth or survival between the two cells emerging from division. One cell can be regarded as an aging mother with a decreased potential for future survival and division, the other as a rejuvenated daughter. Here, we aimed at investigating some of the processes involved in aging in the bacterium Escherichia coli, where the two types of cells can be distinguished by the age of their cell poles. We found that certain changes in the regulation of the carbohydrate metabolism can affect aging. A mutation in the carbon storage regulator gene, csrA, leads to a dramatically shorter replicative lifespan; csrA mutants stop dividing once their pole exceeds an age of about five divisions. These old-pole cells accumulate glycogen at their old cell poles; after their last division, they do not contain a chromosome, presumably because of spatial exclusion by the glycogen aggregates. The new-pole daughters produced by these aging mothers are born young; they only express the deleterious phenotype once their pole is old. These results demonstrate how manipulations of nutrient allocation can lead to the exclusion of the chromosome and limit replicative lifespan in E. coli, and illustrate how mutations can have phenotypic effects that are specific for cells with old poles. This raises the question how bacteria can avoid the accumulation of such mutations in their genomes over evolutionary times, and how they can achieve the long replicative lifespans that have recently been reported.

  5. Genetic Manipulation of Glycogen Allocation Affects Replicative Lifespan in E. coli.

    Directory of Open Access Journals (Sweden)

    Alex Boehm

    2016-04-01

    Full Text Available In bacteria, replicative aging manifests as a difference in growth or survival between the two cells emerging from division. One cell can be regarded as an aging mother with a decreased potential for future survival and division, the other as a rejuvenated daughter. Here, we aimed at investigating some of the processes involved in aging in the bacterium Escherichia coli, where the two types of cells can be distinguished by the age of their cell poles. We found that certain changes in the regulation of the carbohydrate metabolism can affect aging. A mutation in the carbon storage regulator gene, csrA, leads to a dramatically shorter replicative lifespan; csrA mutants stop dividing once their pole exceeds an age of about five divisions. These old-pole cells accumulate glycogen at their old cell poles; after their last division, they do not contain a chromosome, presumably because of spatial exclusion by the glycogen aggregates. The new-pole daughters produced by these aging mothers are born young; they only express the deleterious phenotype once their pole is old. These results demonstrate how manipulations of nutrient allocation can lead to the exclusion of the chromosome and limit replicative lifespan in E. coli, and illustrate how mutations can have phenotypic effects that are specific for cells with old poles. This raises the question how bacteria can avoid the accumulation of such mutations in their genomes over evolutionary times, and how they can achieve the long replicative lifespans that have recently been reported.

  6. Catalpol Modulates Lifespan via DAF-16/FOXO and SKN-1/Nrf2 Activation in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Hyun Won Seo

    2015-01-01

    Full Text Available Catalpol is an effective component of rehmannia root and known to possess various pharmacological properties. The present study was aimed at investigating the potential effects of catalpol on the lifespan and stress tolerance using C. elegans model system. Herein, catalpol showed potent lifespan extension of wild-type nematode under normal culture condition. In addition, survival rate of catalpol-fed nematodes was significantly elevated compared to untreated control under heat and oxidative stress but not under hyperosmolality conditions. We also found that elevated antioxidant enzyme activities and expressions of stress resistance proteins were attributed to catalpol-mediated increased stress tolerance of nematode. We further investigated whether catalpol’s longevity effect is related to aging-related factors including reproduction, food intake, and growth. Interestingly, catalpol exposure could attenuate pharyngeal pumping rate, indicating that catalpol may induce dietary restriction of nematode. Moreover, locomotory ability of aged nematode was significantly improved by catalpol treatment, while lipofuscin levels were attenuated, suggesting that catalpol may affect age-associated changes of nematode. Our mechanistic studies revealed that mek-1, daf-2, age-1, daf-16, and skn-1 are involved in catalpol-mediated longevity. These results indicate that catalpol extends lifespan and increases stress tolerance of C. elegans via DAF-16/FOXO and SKN-1/Nrf activation dependent on insulin/IGF signaling and JNK signaling.

  7. Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Portal-Celhay Cynthia

    2012-03-01

    Full Text Available Abstract Background A powerful approach to understanding complex processes such as aging is to use model organisms amenable to genetic manipulation, and to seek relevant phenotypes to measure. Caenorhabditis elegans is particularly suited to studies of aging, since numerous single-gene mutations have been identified that affect its lifespan; it possesses an innate immune system employing evolutionarily conserved signaling pathways affecting longevity. As worms age, bacteria accumulate in the intestinal tract. However, quantitative relationships between worm genotype, lifespan, and intestinal lumen bacterial load have not been examined. We hypothesized that gut immunity is less efficient in older animals, leading to enhanced bacterial accumulation, reducing longevity. To address this question, we evaluated the ability of worms to control bacterial accumulation as a functional marker of intestinal immunity. Results We show that as adult worms age, several C. elegans genotypes show diminished capacity to control intestinal bacterial accumulation. We provide evidence that intestinal bacterial load, regulated by gut immunity, is an important causative factor of lifespan determination; the effects are specified by bacterial strain, worm genotype, and biologic age, all acting in concert. Conclusions In total, these studies focus attention on the worm intestine as a locus that influences longevity in the presence of an accumulating bacterial population. Further studies defining the interplay between bacterial species and host immunity in C. elegans may provide insights into the general mechanisms of aging and age-related diseases.

  8. EFFECT ON LIFESPAN OF HIGH YIELD NONMYELOABLATING TRANSPLANTATION OF BONE MARROW FROM YOUNG TO OLD MICE

    Directory of Open Access Journals (Sweden)

    Marina eKovina

    2013-08-01

    Full Text Available Tissue renewal is a well-known phenomenon by which old and dying-off cells of various tissues of the body are replaced by progeny of local or circulating stem cells (SC. An interesting question is whether donor stem cells are capable to prolong the lifespan of an ageing organism by tissue renewal.. In this work we investigated the possible use of bone marrow SC for lifespan extension. To this purpose, chimeric C57BL/6 mice were created by transplanting bone marrow from young 1.5-month donors to 21.5-month-old recipients. Transplantation was carried out by means of a recently developed method which allowed to transplant without myeloablation up to 1.5×108 cells, that is, about 25 % of the total BM cells of the mouse. As a result, the mean survival time, counting from the age of 21.5 months, the start of the experiment, was +3.6 and +5.0 (± 0.1 months for the control and experimental groups, respectively, corresponding to a 39% ± 4% increase in the experimental group over the control. In earlier studies on BM transplantation a considerably smaller quantity of donor cells (5×106 was used, about 1 % of the total own BM cells. The recipients before transplantation were exposed to a lethal (for control animals X-ray dose which eliminated the possibility of studying the lifespan extension by this method.

  9. Lamin A, farnesylation and aging

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, Sita [Department of Biochemistry and Molecular Biology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States); Comai, Lucio, E-mail: comai@usc.edu [Department of Molecular Microbiology and Immunology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States)

    2012-01-01

    Lamin A is a component of the nuclear envelope that is synthesized as a precursor prelamin A molecule and then processed into mature lamin A through sequential steps of posttranslational modifications and proteolytic cleavages. Remarkably, over 400 distinct point mutations have been so far identified throughout the LMNA gene, which result in the development of at least ten distinct human disorders, collectively known as laminopathies, among which is the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). The majority of HGPS cases are associated with a single point mutation in the LMNA gene that causes the production of a permanently farnesylated mutant lamin A protein termed progerin. The mechanism by which progerin leads to premature aging and the classical HGPS disease phenotype as well as the relationship between this disorder and the onset of analogous symptoms during the lifespan of a normal individual are not well understood. Yet, recent studies have provided critical insights on the cellular processes that are affected by accumulation of progerin and have suggested that cellular alterations in the lamin A processing pathway leading to the accumulation of farnesylated prelamin A intermediates may play a role in the aging process in the general population. In this review we provide a short background on lamin A and its maturation pathway and discuss the current knowledge of how progerin or alterations in the prelamin A processing pathway are thought to influence cell function and contribute to human aging.

  10. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  11. Evidence That Lifelong Low Dose Rates of Ionizing Radiation Increase Lifespan in Long- and Short-Lived Dogs.

    Science.gov (United States)

    Cuttler, Jerry M; Feinendegen, Ludwig E; Socol, Yehoshua

    2017-01-01

    After the 1956 radiation scare to stop weapons testing, studies focused on cancer induction by low-level radiation. Concern has shifted to protecting "radiation-sensitive individuals." Since longevity is a measure of health impact, this analysis reexamined data to compare the effect of dose rate on the lifespans of short-lived (5% and 10% mortality) dogs and on the lifespans of dogs at 50% mortality. The data came from 2 large-scale studies. One exposed 10 groups to different γ dose rates; the other exposed 8 groups to different lung burdens of plutonium. Reexamination indicated that normalized lifespans increased more for short-lived dogs than for average dogs, when radiation was moderately above background. This was apparent by interpolating between the lifespans of nonirradiated dogs and exposed dogs. The optimum lifespan increase appeared at 50 mGy/y. The threshold for harm (decreased lifespan) was 700 mGy/y for 50% mortality dogs and 1100 mGy/y for short-lived dogs. For inhaled α-emitting particulates, longevity was remarkably increased for short-lived dogs below the threshold for harm. Short-lived dogs seem more radiosensitive than average dogs and they benefit more from low radiation. If dogs model humans, this evidence would support a change to radiation protection policy. Maintaining exposures "as low as reasonably achievable" (ALARA) appears questionable.

  12. Evidence That Lifelong Low Dose Rates of Ionizing Radiation Increase Lifespan in Long- and Short-Lived Dogs

    Science.gov (United States)

    Feinendegen, Ludwig E.; Socol, Yehoshua

    2017-01-01

    After the 1956 radiation scare to stop weapons testing, studies focused on cancer induction by low-level radiation. Concern has shifted to protecting “radiation-sensitive individuals.” Since longevity is a measure of health impact, this analysis reexamined data to compare the effect of dose rate on the lifespans of short-lived (5% and 10% mortality) dogs and on the lifespans of dogs at 50% mortality. The data came from 2 large-scale studies. One exposed 10 groups to different γ dose rates; the other exposed 8 groups to different lung burdens of plutonium. Reexamination indicated that normalized lifespans increased more for short-lived dogs than for average dogs, when radiation was moderately above background. This was apparent by interpolating between the lifespans of nonirradiated dogs and exposed dogs. The optimum lifespan increase appeared at 50 mGy/y. The threshold for harm (decreased lifespan) was 700 mGy/y for 50% mortality dogs and 1100 mGy/y for short-lived dogs. For inhaled α-emitting particulates, longevity was remarkably increased for short-lived dogs below the threshold for harm. Short-lived dogs seem more radiosensitive than average dogs and they benefit more from low radiation. If dogs model humans, this evidence would support a change to radiation protection policy. Maintaining exposures “as low as reasonably achievable” (ALARA) appears questionable.

  13. Environment Aware Cellular Networks

    KAUST Repository

    Ghazzai, Hakim

    2015-02-01

    The unprecedented rise of mobile user demand over the years have led to an enormous growth of the energy consumption of wireless networks as well as the greenhouse gas emissions which are estimated currently to be around 70 million tons per year. This significant growth of energy consumption impels network companies to pay huge bills which represent around half of their operating expenditures. Therefore, many service providers, including mobile operators, are looking for new and modern green solutions to help reduce their expenses as well as the level of their CO2 emissions. Base stations are the most power greedy element in cellular networks: they drain around 80% of the total network energy consumption even during low traffic periods. Thus, there is a growing need to develop more energy-efficient techniques to enhance the green performance of future 4G/5G cellular networks. Due to the problem of traffic load fluctuations in cellular networks during different periods of the day and between different areas (shopping or business districts and residential areas), the base station sleeping strategy has been one of the main popular research topics in green communications. In this presentation, we present several practical green techniques that provide significant gains for mobile operators. Indeed, combined with the base station sleeping strategy, these techniques achieve not only a minimization of the fossil fuel consumption but also an enhancement of mobile operator profits. We start with an optimized cell planning method that considers varying spatial and temporal user densities. We then use the optimal transport theory in order to define the cell boundaries such that the network total transmit power is reduced. Afterwards, we exploit the features of the modern electrical grid, the smart grid, as a new tool of power management for cellular networks and we optimize the energy procurement from multiple energy retailers characterized by different prices and pollutant

  14. The Investigations of Nitric Oxide Influence on Lifespan of Fruit Fly D. melanogaster Transgenic Strain dNOS4

    Directory of Open Access Journals (Sweden)

    Mamura Begmanova

    2014-12-01

    Full Text Available Introduction. Aging and longevity control are among the greatest problems in biology and medicine. The fruit fly Drosophila melanogaster is a nice model organism for longevity investigations because of its biological features. Many D. melanogaster genes have their orthologs, similar in other eukaryotes, including human. The role of nitric oxide (NO in the D. melanogaster lifespan has been analyzed.Methods. Virgin flies of dNOS4 transgenic strain were used for the experiment. This strain contains non-functional additional copies of nitric oxide synthase (NOS gene under heat shock promoter.  For promoter activation, transgenic flies on their second day of life were exposed to heat shock (37°C for an hour. After heat shock, flies were maintained on standard medium temperatures at 25°C, with females separate from males. Two types of control were used: Oregon R wild-type strain and Oregon R strain exposed to heat shock. The average lifespan was evaluated.Results. It was revealed that the longevity of females was significantly higher than males in each series of experiments (p < 0.05. The survival rate of females and males was similar in the first month of their life, but in the second month the mortality among males was much higher than among females in all series of experiments. The average lifespan of dNOS4 imago was 31 days (34 days for females and 28 days for males, maximum lifespan was 63 days. In controls, the average lifespan of Oregon R flies was 54 days (58 days for females and 50 days for males, and the maximum lifespan was 94 days. The average lifespan of Oregon R flies exposed to heat shock was 45 days (48 days for females and 41 days for males, and the maximum lifespan was 72 days. The difference between average lifespan in all studied groups is statistically significant (p < 0.05.Conclusion. Thus, NOS-transgene activation results in formation of non-functional  dNOS4-transcripts and NO deficiency. In turn, NO deficiency decreases d

  15. Cellular communication through light.

    Directory of Open Access Journals (Sweden)

    Daniel Fels

    Full Text Available Information transfer is a fundamental of life. A few studies have reported that cells use photons (from an endogenous source as information carriers. This study finds that cells can have an influence on other cells even when separated with a glass barrier, thereby disabling molecule diffusion through the cell-containing medium. As there is still very little known about the potential of photons for intercellular communication this study is designed to test for non-molecule-based triggering of two fundamental properties of life: cell division and energy uptake. The study was performed with a cellular organism, the ciliate Paramecium caudatum. Mutual exposure of cell populations occurred under conditions of darkness and separation with cuvettes (vials allowing photon but not molecule transfer. The cell populations were separated either with glass allowing photon transmission from 340 nm to longer waves, or quartz being transmittable from 150 nm, i.e. from UV-light to longer waves. Even through glass, the cells affected cell division and energy uptake in neighboring cell populations. Depending on the cuvette material and the number of cells involved, these effects were positive or negative. Also, while paired populations with lower growth rates grew uncorrelated, growth of the better growing populations was correlated. As there were significant differences when separating the populations with glass or quartz, it is suggested that the cell populations use two (or more frequencies for cellular information transfer, which influences at least energy uptake, cell division rate and growth correlation. Altogether the study strongly supports a cellular communication system, which is different from a molecule-receptor-based system and hints that photon-triggering is a fine tuning principle in cell chemistry.

  16. Failover in cellular automata

    CERN Document Server

    Kumar, Shailesh

    2010-01-01

    A cellular automata (CA) configuration is constructed that exhibits emergent failover. The configuration is based on standard Game of Life rules. Gliders and glider-guns form the core messaging structure in the configuration. The blinker is represented as the basic computational unit, and it is shown how it can be recreated in case of a failure. Stateless failover using primary-backup mechanism is demonstrated. The details of the CA components used in the configuration and its working are described, and a simulation of the complete configuration is also presented.

  17. Review of cellular mechanotransduction

    Science.gov (United States)

    Wang, Ning

    2017-06-01

    Living cells and tissues experience physical forces and chemical stimuli in the human body. The process of converting mechanical forces into biochemical activities and gene expression is mechanochemical transduction or mechanotransduction. Significant advances have been made in understanding mechanotransduction at the cellular and molecular levels over the last two decades. However, major challenges remain in elucidating how a living cell integrates signals from mechanotransduction with chemical signals to regulate gene expression and to generate coherent biological responses in living tissues in physiological conditions and diseases.

  18. Cellular automata: structures

    OpenAIRE

    Ollinger, Nicolas

    2002-01-01

    Jury : François Blanchard (Rapporteur), Marianne Delorme (Directeur), Jarkko Kari (Président), Jacques Mazoyer (Directeur), Dominique Perrin, Géraud Sénizergues (Rapporteur); Cellular automata provide a uniform framework to study an important problem of "complex systems" theory: how and why do system with a easily understandable -- local -- microscopic behavior can generate a more complicated -- global -- macroscopic behavior? Since its introduction in the 40s, a lot of work has been done to ...

  19. REDOX REGULATION OF SIRT1 IN INFLAMMATION AND CELLULAR SENESCENCE

    Science.gov (United States)

    Hwang, Jae-woong; Yao, Hongwei; Caito, Samuel; Sundar, Isaac K.; Rahman, Irfan

    2013-01-01

    Sirtuin1 (SIRT1) regulates inflammation, aging (lifespan and healthspan), calorie restriction/energetics, mitochondrial biogenesis, stress resistance, cellular senescence, endothelial functions, apoptosis/autophagy, and circadian rhythms through deacetylation of transcription factors and histones. SIRT1 level and activity are decreased in chronic inflammatory conditions and aging where oxidative stress occurs. SIRT1 is regulated by a NAD+-dependent DNA repair enzyme poly(ADP-ribose)-polymerase-1 (PARP-1), and subsequent NAD+ depletion by oxidative stresses may have consequent effects on inflammatory and stress responses as well as cellular senescence. SIRT1 has been shown to undergo covalent oxidative modifications by cigarette smoke-derived oxidants/aldehydes, leading to post-translational modifications, inactivation, and protein degradation. Furthermore, oxidant/carbonyl stress-mediated reduction of SIRT1 leads to the loss of its control on acetylation of target proteins including p53, RelA/p65 and FOXO3, thereby enhancing the inflammatory, pro-senescent and apoptotic responses, as well as endothelial dysfunction. In this review, the mechanisms of cigarette smoke/oxidant-mediated redox post-translational modifications of SIRT1 and its role in PARP1, NF-κB activation, FOXO3 and eNOS regulation, as well as chromatin remodeling/histone modifications during inflammaging are discussed. Furthermore, we also discussed various novel ways to activate SIRT1 either directly or indirectly, which may have therapeutic potential in attenuating inflammation and premature senescence involved in chronic lung diseases. PMID:23542362

  20. RNA Editing Genes Associated with Extreme Old Age in Humans and with Lifespan in C. elegans

    Science.gov (United States)

    Puca, Annibale; Solovieff, Nadia; Kojima, Toshio; Wang, Meng C.; Melista, Efthymia; Meltzer, Micah; Fischer, Sylvia E. J.; Andersen, Stacy; Hartley, Stephen H.; Sedgewick, Amanda; Arai, Yasumichi; Bergman, Aviv; Barzilai, Nir; Terry, Dellara F.; Riva, Alberto; Anselmi, Chiara Viviani; Malovini, Alberto; Kitamoto, Aya; Sawabe, Motoji; Arai, Tomio; Gondo, Yasuyuki; Steinberg, Martin H.; Hirose, Nobuyoshi; Atzmon, Gil; Ruvkun, Gary; Baldwin, Clinton T.; Perls, Thomas T.

    2009-01-01

    Background The strong familiality of living to extreme ages suggests that human longevity is genetically regulated. The majority of genes found thus far to be associated with longevity primarily function in lipoprotein metabolism and insulin/IGF-1 signaling. There are likely many more genetic modifiers of human longevity that remain to be discovered. Methodology/Principal Findings Here, we first show that 18 single nucleotide polymorphisms (SNPs) in the RNA editing genes ADARB1 and ADARB2 are associated with extreme old age in a U.S. based study of centenarians, the New England Centenarian Study. We describe replications of these findings in three independently conducted centenarian studies with different genetic backgrounds (Italian, Ashkenazi Jewish and Japanese) that collectively support an association of ADARB1 and ADARB2 with longevity. Some SNPs in ADARB2 replicate consistently in the four populations and suggest a strong effect that is independent of the different genetic backgrounds and environments. To evaluate the functional association of these genes with lifespan, we demonstrate that inactivation of their orthologues adr-1 and adr-2 in C. elegans reduces median survival by 50%. We further demonstrate that inactivation of the argonaute gene, rde-1, a critical regulator of RNA interference, completely restores lifespan to normal levels in the context of adr-1 and adr-2 loss of function. Conclusions/Significance Our results suggest that RNA editors may be an important regulator of aging in humans and that, when evaluated in C. elegans, this pathway may interact with the RNA interference machinery to regulate lifespan. PMID:20011587

  1. [The role of the pineal-thymus system in the regulation of autoimmunity, aging and lifespan].

    Science.gov (United States)

    Csaba, György

    2016-07-03

    Thymus is an immunoendocrine organ, the hormones of which mainly influence its own lymphatic elements. It has a central role in the immune system, the neonatal removal causes the collapse of immune system and the whole organism. The thymic nurse cells select the bone marrow originated lymphocytes and destroy the autoreactive ones, while thymus originated Treg cells suppress the autoreactive cells in the periphery. The involution of the organ starts after birth, however, this truly happens in the end of puberty only, as before this it is overcompensated by developmental processes. From the end of adolescence the involution allows the life, proliferation and enhanced functioning of some autoreactive cells, which gradually wear down the cells and intercellular materials, causing the aging. The enhanced and mass function of autoreactive cells lead to the autoimmune diseases and natural death. This means that the involution of thymus is not a part of the organismic involution, but an originator of it, which is manifested in the lifespan-pacemaker function. Thus, aging can be conceptualized as a thymus-commanded slow autoimmune process. The neonatal removal of pineal gland leads to the complete destruction of the thymus and the crashing down of the immune system, as well as to wasting disease. The involution of the pineal and thymus runs parallel, because the two organs form a functional unit. It is probable that the pineal gland is responsible for the involution of thymus and also regulates its lifespan determining role. However, the data reviewed here do not prove the exclusive role of the pineal-thymus system in the regulation of aging and lifespan, but only call attention to such possibility.

  2. Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk.

    Directory of Open Access Journals (Sweden)

    Cathy Slack

    2010-03-01

    Full Text Available Drosophila Lnk is the single ancestral orthologue of a highly conserved family of structurally-related intracellular adaptor proteins, the SH2B proteins. As adaptors, they lack catalytic activity but contain several protein-protein interaction domains, thus playing a critical role in signal transduction from receptor tyrosine kinases to form protein networks. Physiological studies of SH2B function in mammals have produced conflicting data. However, a recent study in Drosophila has shown that Lnk is an important regulator of the insulin/insulin-like growth factor (IGF-1 signaling (IIS pathway during growth, functioning in parallel to the insulin receptor substrate, Chico. As this pathway also has an evolutionary conserved role in the determination of organism lifespan, we investigated whether Lnk is required for normal lifespan in Drosophila. Phenotypic analysis of mutants for Lnk revealed that loss of Lnk function results in increased lifespan and improved survival under conditions of oxidative stress and starvation. Starvation resistance was found to be associated with increased metabolic stores of carbohydrates and lipids indicative of impaired metabolism. Biochemical and genetic data suggest that Lnk functions in both the IIS and Ras/Mitogen activated protein Kinase (MapK signaling pathways. Microarray studies support this model, showing transcriptional feedback onto genes in both pathways as well as indicating global changes in both lipid and carbohydrate metabolism. Finally, our data also suggest that Lnk itself may be a direct target of the IIS responsive transcription factor, dFoxo, and that dFoxo may repress Lnk expression. We therefore describe novel functions for a member of the SH2B protein family and provide the first evidence for potential mechanisms of SH2B regulation. Our findings suggest that IIS signaling in Drosophila may require the activity of a second intracellular adaptor, thereby yielding fundamental new insights into the

  3. A TRPV channel modulates C. elegans neurosecretion, larval starvation survival, and adult lifespan.

    Directory of Open Access Journals (Sweden)

    Brian H Lee

    2008-10-01

    Full Text Available For most organisms, food is only intermittently available; therefore, molecular mechanisms that couple sensation of nutrient availability to growth and development are critical for survival. These mechanisms, however, remain poorly defined. In the absence of nutrients, newly hatched first larval (L1 stage Caenorhabditis elegans halt development and survive in this state for several weeks. We isolated mutations in unc-31, encoding a calcium-activated regulator of neural dense-core vesicle release, which conferred enhanced starvation survival. This extended survival was reminiscent of that seen in daf-2 insulin-signaling deficient mutants and was ultimately dependent on daf-16, which encodes a FOXO transcription factor whose activity is inhibited by insulin signaling. While insulin signaling modulates metabolism, adult lifespan, and dauer formation, insulin-independent mechanisms that also regulate these processes did not promote starvation survival, indicating that regulation of starvation survival is a distinct program. Cell-specific rescue experiments identified a small subset of primary sensory neurons where unc-31 reconstitution modulated starvation survival, suggesting that these neurons mediate perception of food availability. We found that OCR-2, a transient receptor potential vanilloid (TRPV channel that localizes to the cilia of this subset of neurons, regulates peptide-hormone secretion and L1 starvation survival. Moreover, inactivation of ocr-2 caused a significant extension in adult lifespan. These findings indicate that TRPV channels, which mediate sensation of diverse noxious, thermal, osmotic, and mechanical stimuli, couple nutrient availability to larval starvation survival and adult lifespan through modulation of neural dense-core vesicle secretion.

  4. Low-dose rapamycin extends lifespan in a mouse model of mtDNA depletion syndrome.

    Science.gov (United States)

    Siegmund, Stephanie; Yang, Hua; Sharma, Rohit; Javors, Martin; Skinner, Owen; Mootha, Vamsi; Hirano, Michio; Schon, Eric A

    2017-09-01

    Mitochondrial disorders affecting oxidative phosphorylation (OxPhos) are caused by mutations in both the nuclear and mitochondrial genomes. One promising candidate for treatment is the drug rapamycin, which has been shown to extend lifespan in multiple animal models, and which was previously shown to ameliorate mitochondrial disease in a knock-out mouse model lacking a nuclear-encoded gene specifying an OxPhos structural subunit (Ndufs4). In that model, relatively high-dose intraperitoneal rapamycin extended lifespan and improved markers of neurological disease, via an unknown mechanism. Here, we administered low-dose oral rapamycin to a knock-in (KI) mouse model of authentic mtDNA disease, specifically, progressive mtDNA depletion syndrome, resulting from a mutation in the mitochondrial nucleotide salvage enzyme thymidine kinase 2 (TK2). Importantly, low-dose oral rapamycin was sufficient to extend Tk2KI/KI mouse lifespan significantly, and did so in the absence of detectable improvements in mitochondrial dysfunction. We found no evidence that rapamycin increased survival by acting through canonical pathways, including mitochondrial autophagy. However, transcriptomics and metabolomics analyses uncovered systemic metabolic changes pointing to a potential "rapamycin metabolic signature." These changes also implied that rapamycin may have enabled the Tk2KI/KI mice to utilize alternative energy reserves, and possibly triggered indirect signaling events that modified mortality through developmental reprogramming. From a therapeutic standpoint, our results support the possibility that low-dose rapamycin, while not targeting the underlying mtDNA defect, could represent a crucial therapy for the treatment of mtDNA-driven, and some nuclear DNA-driven, mitochondrial diseases. © The Author 2017. Published by Oxford University Press.

  5. Distinct tumor suppressor mechanisms evolve in rodent species that differ in size and lifespan

    Science.gov (United States)

    Seluanov, Andrei; Hine, Christopher; Bozzella, Michael; Hall, Amelia; Sasahara, Tais H. C.; Ribeiro, Antonio A. C. M.; Catania, Kenneth C.; Presgraves, Daven C.; Gorbunova, Vera

    2008-01-01

    SUMMARY Large, long-lived species experience more lifetime cell divisions and hence a greater risk of spontaneous tumor formation than smaller, short-lived species. Large, long-lived species are thus expected to evolve more elaborate tumor suppressor systems. In previous work, we showed that telomerase activity coevolves with body mass, but not lifespan, in rodents: telomerase activity is repressed in the somatic tissues of large rodent species but remains active in small ones. Without telomerase activity, the telomeres of replicating cells become progressively shorter until, at some critical length, cells stop dividing. Our findings therefore suggested that repression of telomerase activity mitigates the increased risk of cancer in larger bodied species but not necessarily longer-lived ones. These findings imply that other tumor suppressor mechanisms must mitigate increased cancer risk in long-lived species. Here, we examined the proliferation of fibroblasts from 15 rodent species with diverse body sizes and lifespans. We show that, consistent with repressed telomerase activity, fibroblasts from large rodents undergo replicative senescence accompanied by telomere shortening and overexpression of p16Ink4a and p21Cip1/Waf1 cycline dependent kinase inhibitors. Interestingly, small rodents with different lifespans show a striking difference: cells from small shorter-lived species display continuous rapid proliferation, whereas cells from small long-lived species display continuous slow proliferation. We hypothesize that cells of small long-lived rodents, lacking replicative senescence, have evolved alternative tumor-suppressor mechanisms that prevent inappropriate cell division in vivo and slow cell growth in vitro. Thus, large-bodied species and small but long-lived species have evolved distinct tumor suppressor mechanisms. PMID:18778411

  6. Within-population Y-linked genetic variation for lifespan in Drosophila melanogaster.

    Science.gov (United States)

    Griffin, R M; Le Gall, D; Schielzeth, H; Friberg, U

    2015-11-01

    The view that the Y chromosome is of little importance for phenotypic evolution stems from early studies of Drosophila melanogaster. This species' Y chromosome contains only 13 protein-coding genes, is almost entirely heterochromatic and is not necessary for male viability. Population genetic theory further suggests that non-neutral variation can only be maintained at the Y chromosome under special circumstances. Yet, recent studies suggest that the D. melanogaster Y chromosome trans-regulates hundreds to thousands of X and autosomal genes. This finding suggests that the Y chromosome may play a far more active role in adaptive evolution than has previously been assumed. To evaluate the potential for the Y chromosome to contribute to phenotypic evolution from standing genetic variation, we test for Y-linked variation in lifespan within a population of D. melanogaster. Assessing variation for lifespan provides a powerful test because lifespan (i) shows sexual dimorphism, which the Y is primarily predicted to contribute to, (ii) is influenced by many genes, which provides the Y with many potential regulatory targets and (iii) is sensitive to heterochromatin remodelling, a mechanism through which the Y chromosome is believed to regulate gene expression. Our results show a small but significant effect of the Y chromosome and thus suggest that the Y chromosome has the potential to respond to selection from standing genetic variation. Despite its small effect size, Y-linked variation may still be important, in particular when evolution of sexual dimorphism is genetically constrained elsewhere in the genome.

  7. Iron-Starvation-Induced Mitophagy Mediates Lifespan Extension upon Mitochondrial Stress in C. elegans.

    Science.gov (United States)

    Schiavi, Alfonso; Maglioni, Silvia; Palikaras, Konstantinos; Shaik, Anjumara; Strappazzon, Flavie; Brinkmann, Vanessa; Torgovnick, Alessandro; Castelein, Natascha; De Henau, Sasha; Braeckman, Bart P; Cecconi, Francesco; Tavernarakis, Nektarios; Ventura, Natascia

    2015-07-20

    Frataxin is a nuclear-encoded mitochondrial protein involved in the biogenesis of Fe-S-cluster-containing proteins and consequently in the functionality of the mitochondrial respiratory chain. Similar to other proteins that regulate mitochondrial respiration, severe frataxin deficiency leads to pathology in humans--Friedreich's ataxia, a life-threatening neurodegenerative disorder--and to developmental arrest in the nematode C. elegans. Interestingly, partial frataxin depletion extends C. elegans lifespan, and a similar anti-aging effect is prompted by reduced expression of other mitochondrial regulatory proteins from yeast to mammals. The beneficial adaptive responses to mild mitochondrial stress are still largely unknown and, if characterized, may suggest novel potential targets for the treatment of human mitochondria-associated, age-related disorders. Here we identify mitochondrial autophagy as an evolutionarily conserved response to frataxin silencing, and show for the first time that, similar to mammals, mitophagy is activated in C. elegans in response to mitochondrial stress in a pdr-1/Parkin-, pink-1/Pink-, and dct-1/Bnip3-dependent manner. The induction of mitophagy is part of a hypoxia-like, iron starvation response triggered upon frataxin depletion and causally involved in animal lifespan extension. We also identify non-overlapping hif-1 upstream (HIF-1-prolyl-hydroxylase) and downstream (globins) regulatory genes mediating lifespan extension upon frataxin and iron depletion. Our findings indicate that mitophagy induction is part of an adaptive iron starvation response induced as a protective mechanism against mitochondrial stress, thus suggesting novel potential therapeutic strategies for the treatment of mitochondrial-associated, age-related disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Lifespan development of attentiveness in domestic dogs: drawing parallels with humans

    Directory of Open Access Journals (Sweden)

    Lisa Jessica Wallis

    2014-02-01

    Full Text Available Attention is pivotal to consciousness, perception, cognition, and working memory in all mammals, and therefore changes in attention over the lifespan are likely to influence development and aging of all of these functions. Due to their evolutionary and developmental history, the dog is being recognised as an important species for modelling human healthspan, aging and associated diseases. In this study, we investigated the normal lifespan development of attentiveness of pet dogs in naturalistic situations, and compared the resulting cross-sectional developmental trajectories with data from previous studies in humans. We tested a sample of 145 Border collies (six months to 14 years with humans and objects or food as attention attractors, in order to assess their attentional capture, sustained and selective attention and sensorimotor abilities. Our results reveal differences in task relevance in sustained attentional performance when watching a human or a moving object, which may be explained by life-long learning processes involving such stimuli. During task-switching we found that dogs’ selective attention and sensorimotor abilities showed differences between age groups, with performance peaking at middle age. Dogs’ sensorimotor abilities showed a quadratic distribution with age and were correlated with selective attention performance. Our results support the hypothesis that the development and senescence of sensorimotor and attentional control may be fundamentally interrelated. Additionally, attentional capture, sustained attention and sensorimotor control developmental trajectories paralleled those found in humans. Given that the development of attention is similar across humans and dogs, we propose that the same regulatory mechanisms are likely to be present in both species. Finally, this cross-sectional study provides the first description of age group changes in attention over the lifespan of pet dogs.

  9. Regional scale patterns of fine root lifespan and turnover under current and future climate.

    Science.gov (United States)

    McCormack, Luke M; Eissenstat, David M; Prasad, Anantha M; Smithwick, Erica A H

    2013-06-01

    Fine root dynamics control a dominant flux of carbon from plants and into soils and mediate potential uptake and cycling of nutrients and water in terrestrial ecosystems. Understanding of these patterns is needed to accurately describe critical processes like productivity and carbon storage from ecosystem to global scales. However, limited observations of root dynamics make it difficult to define and predict patterns of root dynamics across broad spatial scales. Here, we combine species-specific estimates of fine root dynamics with a model that predicts current distribution and future suitable habitat of temperate tree species across the eastern United States (US). Estimates of fine root lifespan and turnover are based on empirical observations and relationships with fine root and whole-plant traits and apply explicitly to the fine root pool that is relatively short-lived and most active in nutrient and water uptake. Results from the combined model identified patterns of faster root turnover rates in the North Central US and slower turnover rates in the Southeastern US. Portions of Minnesota, Ohio, and Pennsylvania were also predicted to experience >10% increases in root turnover rates given potential shifts in tree species composition under future climate scenarios while root turnover rates in other portions of the eastern US were predicted to decrease. Despite potential regional changes, the average estimates of root lifespan and turnover for the entire study area remained relatively stable between the current and future climate scenarios. Our combined model provides the first empirically based, spatially explicit, and spatially extensive estimates of fine root lifespan and turnover and is a potentially powerful tool allowing researchers to identify reasonable approximations of forest fine root turnover in areas where no direct observations are available. Future efforts should focus on reducing uncertainty in estimates of root dynamics by better understanding how

  10. Lifespan Development of the Human Brain Revealed by Large-Scale Network Eigen-Entropy

    Directory of Open Access Journals (Sweden)

    Yiming Fan

    2017-09-01

    Full Text Available Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying functional connectivity patterns of the developing and aging brain. Normal brain development is characterized by continuous and significant network evolution through infancy, childhood, and adolescence, following specific maturational patterns. Normal aging is related to some resting state brain networks disruption, which are associated with certain cognitive decline. It is a big challenge to design an integral metric to track connectome evolution patterns across the lifespan, which is to understand the principles of network organization in the human brain. In this study, we first defined a brain network eigen-entropy (NEE based on the energy probability (EP of each brain node. Next, we used the NEE to characterize the lifespan orderness trajectory of the whole-brain functional connectivity of 173 healthy individuals ranging in age from 7 to 85 years. The results revealed that during the lifespan, the whole-brain NEE exhibited a significant non-linear decrease and that the EP distribution shifted from concentration to wide dispersion, implying orderness enhancement of functional connectome over age. Furthermore, brain regions with significant EP changes from the flourishing (7–20 years to the youth period (23–38 years were mainly located in the right prefrontal cortex and basal ganglia, and were involved in emotion regulation and executive function in coordination with the action of the sensory system, implying that self-awareness and voluntary control performance significantly changed during neurodevelopment. However, the changes from the youth period to middle age (40–59 years were located in the mesial temporal lobe and caudate, which are associated with long-term memory, implying that the memory of the human brain begins to decline with age during this period. Overall, the findings suggested that the human connectome

  11. Lifespan development of attentiveness in domestic dogs: drawing parallels with humans.

    Science.gov (United States)

    Wallis, Lisa J; Range, Friederike; Müller, Corsin A; Serisier, Samuel; Huber, Ludwig; Zsó, Virányi

    2014-01-01

    Attention is pivotal to consciousness, perception, cognition, and working memory in all mammals, and therefore changes in attention over the lifespan are likely to influence development and aging of all of these functions. Due to their evolutionary and developmental history, the dog is being recognized as an important species for modeling human healthspan, aging and associated diseases. In this study, we investigated the normal lifespan development of attentiveness of pet dogs in naturalistic situations, and compared the resulting cross-sectional developmental trajectories with data from previous studies in humans. We tested a sample of 145 Border collies (6 months to 14 years) with humans and objects or food as attention attractors, in order to assess their attentional capture, sustained and selective attention, and sensorimotor abilities. Our results reveal differences in task relevance in sustained attentional performance when watching a human or a moving object, which may be explained by life-long learning processes involving such stimuli. During task switching we found that dogs' selective attention and sensorimotor abilities showed differences between age groups, with performance peaking at middle age. Dogs' sensorimotor abilities showed a quadratic distribution with age and were correlated with selective attention performance. Our results support the hypothesis that the development and senescence of sensorimotor and attentional control may be fundamentally interrelated. Additionally, attentional capture, sustained attention, and sensorimotor control developmental trajectories paralleled those found in humans. Given that the development of attention is similar across humans and dogs, we propose that the same regulatory mechanisms are likely to be present in both species. Finally, this cross-sectional study provides the first description of age group changes in attention over the lifespan of pet dogs.

  12. MicroRNAs miR-203-3p, miR-664-3p and miR-708-5p are associated with median strain lifespan in mice

    Science.gov (United States)

    Lee, Benjamin P.; Burić, Ivana; George-Pandeth, Anupriya; Flurkey, Kevin; Harrison, David E.; Yuan, Rong; Peters, Luanne L.; Kuchel, George A.; Melzer, David; Harries, Lorna W.

    2017-01-01

    MicroRNAs (miRNAs) are small non-coding RNA species that have been shown to have roles in multiple processes that occur in higher eukaryotes. They act by binding to specific sequences in the 3’ untranslated region of their target genes and causing the transcripts to be degraded by the RNA-induced silencing complex (RISC). MicroRNAs have previously been reported to demonstrate altered expression in several aging phenotypes such as cellular senescence and age itself. Here, we have measured the expression levels of 521 small regulatory microRNAs (miRNAs) in spleen tissue from young and old animals of 6 mouse strains with different median strain lifespans by quantitative real-time PCR. Expression levels of 3 microRNAs were robustly associated with strain lifespan, after correction for multiple statistical testing (miR-203-3p [β-coefficient = −0.6447, p = 4.8 × 10−11], miR-664-3p [β-coefficient = 0.5552, p = 5.1 × 10−8] and miR-708-5p [β-coefficient = 0.4986, p = 1.6 × 10−6]). Pathway analysis of binding sites for these three microRNAs revealed enrichment of target genes involved in key aging and longevity pathways including mTOR, FOXO and MAPK, most of which also demonstrated associations with longevity. Our results suggests that miR-203-3p, miR-664-3p and miR-708-5p may be implicated in pathways determining lifespan in mammals. PMID:28304372

  13. [The effect of SSH&H on the lifespan and spontaneous cancer development in transgenic mice with HER-2/neu mutation].

    Science.gov (United States)

    Tyndyk, M L; Popovich, I G; Anikin, I V; Egormin, P A; Iurova, M N; Zabezhinskiĭ, M A; Anisimov, V N

    2012-01-01

    10 months old mice receiving SSH&H with daily food increased the lifespan in comparison to the control group. The maximal lifespan was increased by 1,6 months. For the long-living 10% group the mean lifespan increased by 8,7% compared to the control group (pSSH&H on the neoplastic rate in transgenic mice with HER-2/neu mutation.

  14. Cell specific radiation dosimetry in skeleton from life-span carcinogenesis studies. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Webster, S.S.J.

    1993-04-05

    The osteogenic sarcoma is the dominant life-threatening pathology in lifespan studies of beagles exposed to alpha-emitting bone-seeking radionuclides. It was deduced from these studies that certain skeletal sites are more prone to develop tumors. This project sought to determine the bone cells at risk and their cell-specific radiation dose. The cell-specific radiation dose values are related to loss and high Ra-226 and Pu-239 induced osteogenic sarcoma sites, to test different dose response hypothesis and predict the extent of effects in humans.

  15. Telomerase inhibitor Imetelstat (GRN163L limits the lifespan of human pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Katrina M Burchett

    Full Text Available Telomerase is required for the unlimited lifespan of cancer cells. The vast majority of pancreatic adenocarcinomas overexpress telomerase activity and blocking telomerase could limit their lifespan. GRN163L (Imetelstat is a lipid-conjugated N3'→P5' thio-phosphoramidate oligonucleotide that blocks the template region of telomerase. The aim of this study was to define the effects of long-term GRN163L exposure on the maintenance of telomeres and lifespan of pancreatic cancer cells. Telomere size, telomerase activity, and telomerase inhibition response to GRN163L were measured in a panel of 10 pancreatic cancer cell lines. The cell lines exhibited large differences in levels of telomerase activity (46-fold variation, but most lines had very short telomeres (2-3 kb in size. GRN163L inhibited telomerase in all 10 pancreatic cancer cell lines, with IC50 ranging from 50 nM to 200 nM. Continuous GRN163L exposure of CAPAN1 (IC50 = 75 nM and CD18 cells (IC50 = 204 nM resulted in an initial rapid shortening of the telomeres followed by the maintenance of extremely short but stable telomeres. Continuous exposure to the drug eventually led to crisis and to a complete loss of viability after 47 (CAPAN1 and 69 (CD18 doublings. Crisis In these cells was accompanied by activation of a DNA damage response (γ-H2AX and evidence of both senescence (SA-β-galactosidase activity and apoptosis (sub-G1 DNA content, PARP cleavage. Removal of the drug after long-term GRN163L exposure led to a reactivation of telomerase and re-elongation of telomeres in the third week of cultivation without GRN163L. These findings show that the lifespan of pancreatic cancer cells can be limited by continuous telomerase inhibition. These results should facilitate the design of future clinical trials of GRN163L in patients with pancreatic cancer.

  16. Telomerase inhibitor Imetelstat (GRN163L) limits the lifespan of human pancreatic cancer cells.

    Science.gov (United States)

    Burchett, Katrina M; Yan, Ying; Ouellette, Michel M

    2014-01-01

    Telomerase is required for the unlimited lifespan of cancer cells. The vast majority of pancreatic adenocarcinomas overexpress telomerase activity and blocking telomerase could limit their lifespan. GRN163L (Imetelstat) is a lipid-conjugated N3'→P5' thio-phosphoramidate oligonucleotide that blocks the template region of telomerase. The aim of this study was to define the effects of long-term GRN163L exposure on the maintenance of telomeres and lifespan of pancreatic cancer cells. Telomere size, telomerase activity, and telomerase inhibition response to GRN163L were measured in a panel of 10 pancreatic cancer cell lines. The cell lines exhibited large differences in levels of telomerase activity (46-fold variation), but most lines had very short telomeres (2-3 kb in size). GRN163L inhibited telomerase in all 10 pancreatic cancer cell lines, with IC50 ranging from 50 nM to 200 nM. Continuous GRN163L exposure of CAPAN1 (IC50 = 75 nM) and CD18 cells (IC50 = 204 nM) resulted in an initial rapid shortening of the telomeres followed by the maintenance of extremely short but stable telomeres. Continuous exposure to the drug eventually led to crisis and to a complete loss of viability after 47 (CAPAN1) and 69 (CD18) doublings. Crisis In these cells was accompanied by activation of a DNA damage response (γ-H2AX) and evidence of both senescence (SA-β-galactosidase activity) and apoptosis (sub-G1 DNA content, PARP cleavage). Removal of the drug after long-term GRN163L exposure led to a reactivation of telomerase and re-elongation of telomeres in the third week of cultivation without GRN163L. These findings show that the lifespan of pancreatic cancer cells can be limited by continuous telomerase inhibition. These results should facilitate the design of future clinical trials of GRN163L in patients with pancreatic cancer.

  17. Ovarian Reserve Assessment in Users of Oral Contraception Seeking Fertility Advice on their Reproductive Lifespan

    DEFF Research Database (Denmark)

    Petersen, K. Birch; Hvidman, H. W.; Forman, J. L.;

    2016-01-01

    STUDY QUESTION: To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced? SUMMARY ANSWER: Ovarian reserve parameters defined by anti...... and the contraceptive vaginal ring). Non-users included women with an intrauterine device (IUD) or no hormonal contraception. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 887 women, 244 (27.5%) used OC. In a linear regression analyses adjusted for age, ovarian volume was 50% lower (95% CI 45.1-53.7%), AMH was 19% lower...

  18. Ovarian reserve assessment in users of oral contraception seeking fertility advice on their reproductive lifespan

    DEFF Research Database (Denmark)

    Birch Petersen, K; Hvidman, H W; Forman, J L;

    2015-01-01

    STUDY QUESTION: To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced? SUMMARY ANSWER: Ovarian reserve parameters defined by anti...... and the contraceptive vaginal ring). Non-users included women with an intrauterine device (IUD) or no hormonal contraception. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 887 women, 244 (27.5%) used OC. In a linear regression analyses adjusted for age, ovarian volume was 50% lower (95% CI 45.1-53.7%), AMH was 19% lower...

  19. Life-span of classical solutions for one-dimensional hydromagnetic flow

    Institute of Scientific and Technical Information of China (English)

    LIU Fa-gui

    2007-01-01

    The paper concerns Cauchy problem for one-dimensional hydromagnetic dynamics with dissipative terms. When the dissipation coefficient is equal to zero it is shown that the smooth solutions develop shocks in the finite time if the initial amounts of entropy and magnetic field are smaller than those of sound waves; when it is larger than zero, and the initial amounts of entropy, this dissipation coefficient and the magnetic field in each period are smaller than those of sound waves, then the smooth solutions blow up in the finite time. Moreover, the life-span of the smooth solution is given.

  20. Survival to reproductive cessation drives variation in post-reproductive lifespan

    DEFF Research Database (Denmark)

    Proske, Beate; Burger, Oskar; Levitis, Daniel

    2014-01-01

    How many post-reproductive individuals are found in a population depends on how many individuals survive to reproductive cessation and how long they live thereafter. Post-reproductive Representation (PrR), a measure of post-reproductive lifespan intended for interspecific comparisons, allows...... the majority of variation in PrR among a group of small cohorts of rotifers, and among several historical Swedish cohorts. We emphasize that women are distinct from other primates in the proportion reaching reproductive cessation, but not in the proportion of adult life-expectancy that is post...

  1. The effect of Emblica officinalis diet on lifespan, sexual behavior, and fitness characters in Drosophila melanogaster.

    Science.gov (United States)

    Pathak, Pankaj; Prasad, B R Guru; Murthy, N Anjaneya; Hegde, S N

    2011-04-01

    Drosophila is an excellent organism to test Ayurvedic medicines. The objective of our study was to explore the potential of Emblica officinalis drug on longevity, sexual behavior, and reproductive fitness of Drosophila melanogaster using adult feeding method. Increase in the lifespan, fecundity, fertility, ovarioles number, and developmental time was observed in both parents and F1 generation, but not in the F2 generation in experimental culture (control + E. officinalis). According to the Duncan's multiple range test and ANOVA, there is a significant difference between two cultures. It was also noticed that E. officinalis influence some fitness characters in Drosophila along with sexual behavior.

  2. Cell specific radiation dosimetry in skeleton from life-span carcinogenesis studies

    Energy Technology Data Exchange (ETDEWEB)

    Webster, S.S.J.

    1993-04-05

    The osteogenic sarcoma is the dominant life-threatening pathology in lifespan studies of beagles exposed to alpha-emitting bone-seeking radionuclides. It was deduced from these studies that certain skeletal sites are more prone to develop tumors. This project sought to determine the bone cells at risk and their cell-specific radiation dose. The cell-specific radiation dose values are related to loss and high Ra-226 and Pu-239 induced osteogenic sarcoma sites, to test different dose response hypothesis and predict the extent of effects in humans.

  3. [Senescence and cellular immortality].

    Science.gov (United States)

    Trentesaux, C; Riou, J-F

    2010-11-01

    Senescence was originally described from the observation of the limited ability of normal cells to grow in culture, and may be generated by telomere erosion, accumulation of DNA damages, oxidative stress and modulation of oncogenes or tumor suppressor genes. Senescence corresponds to a cellular response aiming to control tumor progression by limiting cell proliferation and thus constitutes an anticancer barrier. Senescence is observed in pre-malignant tumor stages and disappears from malignant tumors. Agents used in standard chemotherapy also have the potential to induce senescence, which may partly explain their therapeutic activities. It is possible to restore senescence in tumors using targeted therapies that triggers telomere dysfunction or reactivates suppressor genes functions, which are essential for the onset of senescence.

  4. Engineering Cellular Metabolism.

    Science.gov (United States)

    Nielsen, Jens; Keasling, Jay D

    2016-03-10

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds, and pharmaceuticals. However, making cells into efficient factories is challenging because cells have evolved robust metabolic networks with hard-wired, tightly regulated lines of communication between molecular pathways that resist efforts to divert resources. Here, we will review the current status and challenges of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation.

  5. Cellular image classification

    CERN Document Server

    Xu, Xiang; Lin, Feng

    2017-01-01

    This book introduces new techniques for cellular image feature extraction, pattern recognition and classification. The authors use the antinuclear antibodies (ANAs) in patient serum as the subjects and the Indirect Immunofluorescence (IIF) technique as the imaging protocol to illustrate the applications of the described methods. Throughout the book, the authors provide evaluations for the proposed methods on two publicly available human epithelial (HEp-2) cell datasets: ICPR2012 dataset from the ICPR'12 HEp-2 cell classification contest and ICIP2013 training dataset from the ICIP'13 Competition on cells classification by fluorescent image analysis. First, the reading of imaging results is significantly influenced by one’s qualification and reading systems, causing high intra- and inter-laboratory variance. The authors present a low-order LP21 fiber mode for optical single cell manipulation and imaging staining patterns of HEp-2 cells. A focused four-lobed mode distribution is stable and effective in optical...

  6. Multiuser Cellular Network

    CERN Document Server

    Bao, Yi; Chen, Ming

    2011-01-01

    Modern radio communication is faced with a problem about how to distribute restricted frequency to users in a certain space. Since our task is to minimize the number of repeaters, a natural idea is enlarging coverage area. However, coverage has restrictions. First, service area has to be divided economically as repeater's coverage is limited. In this paper, our fundamental method is to adopt seamless cellular network division. Second, underlying physics content in frequency distribution problem is interference between two close frequencies. Consequently, we choose a proper frequency width of 0.1MHz and a relevantly reliable setting to apply one frequency several times. We make a few general assumptions to simplify real situation. For instance, immobile users yield to homogenous distribution; repeaters can receive and transmit information in any given frequency in duplex operation; coverage is mainly decided by antenna height. Two models are built up to solve 1000 users and 10000 users situations respectively....

  7. Extension of Drosophila lifespan by cinnamon through a sex-specific dependence on the insulin receptor substrate chico.

    Science.gov (United States)

    Schriner, Samuel E; Kuramada, Steven; Lopez, Terry E; Truong, Stephanie; Pham, Andrew; Jafari, Mahtab

    2014-12-01

    Cinnamon is a spice commonly used worldwide to flavor desserts, fruits, cereals, breads, and meats. Numerous health benefits have been attributed to its consumption, including the recent suggestion that it may decrease blood glucose levels in people with diabetes. Insulin signaling is an integral pathway regulating the lifespan of laboratory organisms, such as worms, flies, and mice. We posited that if cinnamon truly improved the clinical signs of diabetes in people that it would also act on insulin signaling in laboratory organisms and increase lifespan. We found that cinnamon did extend lifespan in the fruit fly, Drosophila melanogaster. However, it had no effect on the expression levels of the 3 aging-related Drosophila insulin-like peptides nor did it alter sugar, fat, or soluble protein levels, as would be predicted. In addition, cinnamon exhibited no protective effects in males against oxidative challenges. However, in females it did confer a protective effect against paraquat, but sensitized them to iron. Cinnamon provided no protective effect against desiccation and starvation in females, but sensitized males to both. Interestingly, cinnamon protected both sexes against cold, sensitized both to heat, and elevated HSP70 expression levels. We also found that cinnamon required the insulin receptor substrate to extend lifespan in males, but not females. We conclude that cinnamon does not extend lifespan by improving stress tolerance in general, though it does act, at least in part, through insulin signaling.

  8. A transcription elongation factor that links signals from the reproductive system to lifespan extension in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Arjumand Ghazi

    2009-09-01

    Full Text Available In Caenorhabditis elegans and Drosophila melanogaster, the aging of the soma is influenced by the germline. When germline-stem cells are removed, aging slows and lifespan is increased. The mechanism by which somatic tissues respond to loss of the germline is not well-understood. Surprisingly, we have found that a predicted transcription elongation factor, TCER-1, plays a key role in this process. TCER-1 is required for loss of the germ cells to increase C. elegans' lifespan, and it acts as a regulatory switch in the pathway. When the germ cells are removed, the levels of TCER-1 rise in somatic tissues. This increase is sufficient to trigger key downstream events, as overexpression of tcer-1 extends the lifespan of normal animals that have an intact reproductive system. Our findings suggest that TCER-1 extends lifespan by promoting the expression of a set of genes regulated by the conserved, life-extending transcription factor DAF-16/FOXO. Interestingly, TCER-1 is not required for DAF-16/FOXO to extend lifespan in animals with reduced insulin/IGF-1 signaling. Thus, TCER-1 specifically links the activity of a broadly deployed transcription factor, DAF-16/FOXO, to longevity signals from reproductive tissues.

  9. Development of a method to estimate the lifespan of proton exchange membrane fuel cell using electrochemical impedance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ju-hyung; Lee, Jong-Hak; Choi, Woojin [Department of Electrical Engineering, Soongsil University, 1-1 Sangdo-dong, Dongjak-gu, Seoul 156-743 (Korea); Park, Kyung-Won [Department of Chemical/Environmental Engineering, Soongsil University, 1-1 Sangdo-dong, Dongjak-gu, Seoul 156-743 (Korea); Sun, Hee-Young [Samsung Advanced Institute of Technology, Mt. 14-1, Nongseo-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-712 (Korea); Oh, Jae-Hyuk [Samsung Electronics, 416 Maetan-dong, Youngtong-gu, Suwon-si, Gyeonggi-do 443-370 (Korea)

    2010-09-15

    This paper proposes a new method for estimating the state and lifespan of fuel cells in operation by fuel cell equivalent impedance modeling by electrochemical impedance spectroscopy (EIS) and observing degradation. The performance change of fuel cells takes place in the form of changes in each parameter value comprising an equivalent AC impedance circuit; monitoring such changes allows for the prediction of the state and lifespan of a fuel cell. In the experiments, the AC impedance of high-temperature proton exchange membrane (PEM) fuel cells was measured at constant time intervals during their continuous operation for over 2200 h. The expression for the lifespan of a fuel cell was deduced by curve fitting the changes in each parameter to a polynomial. Electric double layer capacitance and charge transfer resistance, which show the reduction reaction of the cathode, were used as major parameters for judging the degradation; a method of using time constants is proposed to more accurately estimate the degree of degradation. In addition, an algorithm that can evaluate the soundness and lifespan of a fuel cell is proposed; it compares the measured time constant of the fuel cell being tested with that of average lifespan fuel cell. (author)

  10. Lithocholic bile acid accumulated in yeast mitochondria orchestrates a development of an anti-aging cellular pattern by causing age-related changes in cellular proteome.

    Science.gov (United States)

    Beach, Adam; Richard, Vincent R; Bourque, Simon; Boukh-Viner, Tatiana; Kyryakov, Pavlo; Gomez-Perez, Alejandra; Arlia-Ciommo, Anthony; Feldman, Rachel; Leonov, Anna; Piano, Amanda; Svistkova, Veronika; Titorenko, Vladimir I

    2015-01-01

    We have previously revealed that exogenously added lithocholic bile acid (LCA) extends the chronological lifespan of the yeast Saccharomyces cerevisiae, accumulates in mitochondria and alters mitochondrial membrane lipidome. Here, we use quantitative mass spectrometry to show that LCA alters the age-related dynamics of changes in levels of many mitochondrial proteins, as well as numerous proteins in cellular locations outside of mitochondria. These proteins belong to 2 regulons, each modulated by a different mitochondrial dysfunction; we call them a partial mitochondrial dysfunction regulon and an oxidative stress regulon. We found that proteins constituting these regulons (1) can be divided into several "clusters", each of which denotes a distinct type of partial mitochondrial dysfunction that elicits a different signaling pathway mediated by a discrete set of transcription factors; (2) exhibit 3 different patterns of the age-related dynamics of changes in their cellular levels; and (3) are encoded by genes whose expression is regulated by the transcription factors Rtg1p/Rtg2p/Rtg3p, Sfp1p, Aft1p, Yap1p, Msn2p/Msn4p, Skn7p and Hog1p, each of which is essential for longevity extension by LCA. Our findings suggest that LCA-driven changes in mitochondrial lipidome alter mitochondrial proteome and functionality, thereby enabling mitochondria to operate as signaling organelles that orchestrate an establishment of an anti-aging transcriptional program for many longevity-defining nuclear genes. Based on these findings, we propose a model for how such LCA-driven changes early and late in life of chronologically aging yeast cause a stepwise development of an anti-aging cellular pattern and its maintenance throughout lifespan.

  11. Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan.

    Science.gov (United States)

    Liu, Zhi-Jian; Hoffmeister, Karin M; Hu, Zhongbo; Mager, Donald E; Ait-Oudhia, Sihem; Debrincat, Marlyse A; Pleines, Irina; Josefsson, Emma C; Kile, Benjamin T; Italiano, Joseph; Ramsey, Haley; Grozovsky, Renata; Veng-Pedersen, Peter; Chavda, Chaitanya; Sola-Visner, Martha

    2014-05-29

    The fetal/neonatal hematopoietic system must generate enough blood cells to meet the demands of rapid growth. This unique challenge might underlie the high incidence of thrombocytopenia among preterm neonates. In this study, neonatal platelet production and turnover were investigated in newborn mice. Based on a combination of blood volume expansion and increasing platelet counts, the platelet mass increased sevenfold during the first 2 weeks of murine life, a time during which thrombopoiesis shifted from liver to bone marrow. Studies applying in vivo biotinylation and mathematical modeling showed that newborn and adult mice had similar platelet production rates, but neonatal platelets survived 1 day longer in circulation. This prolonged lifespan fully accounted for the rise in platelet counts observed during the second week of murine postnatal life. A study of pro-apoptotic and anti-apoptotic Bcl-2 family proteins showed that neonatal platelets had higher levels of the anti-apoptotic protein Bcl-2 and were more resistant to apoptosis induced by the Bcl-2/Bcl-xL inhibitor ABT-737 than adult platelets. However, genetic ablation or pharmacologic inhibition of Bcl-2 alone did not shorten neonatal platelet survival or reduce platelet counts in newborn mice, indicating the existence of redundant or alternative mechanisms mediating the prolonged lifespan of neonatal platelets. © 2014 by The American Society of Hematology.

  12. Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB.

    Science.gov (United States)

    Mair, William; Morantte, Ianessa; Rodrigues, Ana P C; Manning, Gerard; Montminy, Marc; Shaw, Reuben J; Dillin, Andrew

    2011-02-17

    Activating AMPK or inactivating calcineurin slows ageing in Caenorhabditis elegans and both have been implicated as therapeutic targets for age-related pathology in mammals. However, the direct targets that mediate their effects on longevity remain unclear. In mammals, CREB-regulated transcriptional coactivators (CRTCs) are a family of cofactors involved in diverse physiological processes including energy homeostasis, cancer and endoplasmic reticulum stress. Here we show that both AMPK and calcineurin modulate longevity exclusively through post-translational modification of CRTC-1, the sole C. elegans CRTC. We demonstrate that CRTC-1 is a direct AMPK target, and interacts with the CREB homologue-1 (CRH-1) transcription factor in vivo. The pro-longevity effects of activating AMPK or deactivating calcineurin decrease CRTC-1 and CRH-1 activity and induce transcriptional responses similar to those of CRH-1 null worms. Downregulation of crtc-1 increases lifespan in a crh-1-dependent manner and directly reducing crh-1 expression increases longevity, substantiating a role for CRTCs and CREB in ageing. Together, these findings indicate a novel role for CRTCs and CREB in determining lifespan downstream of AMPK and calcineurin, and illustrate the molecular mechanisms by which an evolutionarily conserved pathway responds to low energy to increase longevity.

  13. A comprehensive approach to the molecular determinants of lifespan using a Boolean model of geroconversion.

    Science.gov (United States)

    Verlingue, Loic; Dugourd, Aurélien; Stoll, Gautier; Barillot, Emmanuel; Calzone, Laurence; Londoño-Vallejo, Arturo

    2016-09-09

    Altered molecular responses to insulin and growth factors (GF) are responsible for late-life shortening diseases such as type-2 diabetes mellitus (T2DM) and cancers. We have built a network of the signaling pathways that control S-phase entry and a specific type of senescence called geroconversion. We have translated this network into a Boolean model to study possible cell phenotype outcomes under diverse molecular signaling conditions. In the context of insulin resistance, the model was able to reproduce the variations of the senescence level observed in tissues related to T2DM's main morbidity and mortality. Furthermore, by calibrating the pharmacodynamics of mTOR inhibitors, we have been able to reproduce the dose-dependent effect of rapamycin on liver degeneration and lifespan expansion in wild-type and HER2-neu mice. Using the model, we have finally performed an in silico prospective screen of the risk-benefit ratio of rapamycin dosage for healthy lifespan expansion strategies. We present here a comprehensive prognostic and predictive systems biology tool for human aging.

  14. Migratory management and environmental conditions affect lifespan and oxidative stress in honey bees

    Science.gov (United States)

    Simone-Finstrom, Michael; Li-Byarlay, Hongmei; Huang, Ming H.; Strand, Micheline K.; Rueppell, Olav; Tarpy, David R.

    2016-01-01

    Most pollination in large-scale agriculture is dependent on managed colonies of a single species, the honey bee Apis mellifera. More than 1 million hives are transported to California each year just to pollinate the almonds, and bees are trucked across the country for various cropping systems. Concerns have been raised about whether such “migratory management” causes bees undue stress; however to date there have been no longer-term studies rigorously addressing whether migratory management is detrimental to bee health. To address this issue, we conducted field experiments comparing bees from commercial and experimental migratory beekeeping operations to those from stationary colonies to quantify effects on lifespan, colony health and productivity, and levels of oxidative damage for individual bees. We detected a significant decrease in lifespan of migratory adult bees relative to stationary bees. We also found that migration affected oxidative stress levels in honey bees, but that food scarcity had an even larger impact; some detrimental effects of migration may be alleviated by a greater abundance of forage. In addition, rearing conditions affect levels of oxidative damage incurred as adults. This is the first comprehensive study on impacts of migratory management on the health and oxidative stress of honey bees. PMID:27554200

  15. Lifespan is unrelated to investment in reproduction in populations of mammals and birds in captivity.

    Science.gov (United States)

    Ricklefs, Robert E; Cadena, Carlos Daniel

    2007-10-01

    We examined the relationship between number of offspring produced to a certain age and subsequent longevity in captive zoo populations of 18 species of mammal and 12 species of bird. The age cut-offs in each analysis were set to include 50%, 75% and 90% of the offspring produced in each of the population samples. Only one of 68 regressions was significant, and its slope was positive. In addition, we examined the relationship between age at first reproduction up to a certain age and longevity after that age, generally 5 years (3-8), among 17 species of mammal and 12 species of bird. Only one of these regressions had a significantly positive slope, indicating that early reproduction rarely reduces lifespan. Overall, we found no evidence that producing offspring in a zoo environment influences the age at death. Thus, although trade-offs might apply in natural populations under resource limitation, neither pregnancy, growth of the foetus and lactation in mammals, nor egg production in birds, reduces lifespan in the absence of such stress. If genetically based or other intrinsic antagonistic pleiotropy underlies the evolution of senescence, it was not evident in our analyses.

  16. Uneven futures of human lifespans: reckonings from Gompertz mortality rates, climate change, and air pollution.

    Science.gov (United States)

    Finch, Caleb E; Beltrán-Sánchez, Hiram; Crimmins, Eileen M

    2014-01-01

    The past 200 years have enabled remarkable increases in human lifespans through improvements in the living environment that have nearly eliminated infections as a cause of death through improved hygiene, public health, medicine, and nutrition. We argue that the limit to lifespan may be approaching. Since 1997, no one has exceeded Jeanne Calment's record of 122.5 years, despite an exponential increase of centenarians. Moreover, the background mortality may be approaching a lower limit. We calculate from Gompertz coefficients that further increases in longevity to approach a life expectancy of 100 years in 21st century cohorts would require 50% slower mortality rate accelerations, which would be a fundamental change in the rate of human aging. Looking into the 21st century, we see further challenges to health and longevity from the continued burning of fossil fuels that contribute to air pollution as well as global warming. Besides increased heat waves to which elderly are vulnerable, global warming is anticipated to increase ozone levels and facilitate the spread of pathogens. We anticipate continuing socioeconomic disparities in life expectancy.

  17. Asymmetry in stimulus and response conflict processing across the adult lifespan: ERP and EMG evidence.

    Science.gov (United States)

    Killikelly, Clare; Szűcs, Dénes

    2013-01-01

    Several studies have shown that conflict processing improves from childhood to adulthood and declines from adulthood to old age. However the neural mechanisms underlying this lifespan asymmetry were previously unexplored. We combined event-related potentials (ERPs) and electromyography (EMG) to examine lifespan changes in stimulus and response conflict processing using a modified Stroop task. We used a Stroop task that a priori dissociated stimulus and response conflict. Delayed P3b latency and increased amplitude revealed that middle age adults have a deficit in stimulus processing. Additionally a sustained P3a across frontal and central electrodes occurred only in middle age adults indicating the recruitment of frontal activity. Conversely, decreased lateralized readiness potential (LRP) amplitude and increased EMG activity in the incorrect hand in adolescents reveal protracted development of response processing into late adolescence. The N450, a measure of conflict processing, was found to be sensitive to both stimulus and response conflict. Altogether these results provide evidence for asymmetrical differences in stimulus and response conflict processing across adolescence, young adulthood and middle age.

  18. Crocus sativus L. protects against SDS‑induced intestinal damage and extends lifespan in Drosophila melanogaster.

    Science.gov (United States)

    Liu, Zonglin; Chen, Yuchen; Zhang, Hong; Jin, Li Hua

    2016-12-01

    Medicinal plants are important sources of potentially therapeutic biochemical drugs. Crocus sativus L. has been used to treat various diseases in China, the Republic of Korea and Japan. The present study investigated the protective effect of C. sativus L. extract in Drosophila melanogaster intestinal immunity. Wild‑type flies were fed standard cornmeal‑yeast medium and used as controls, and flies supplemented with 1% C. sativus L. aqueous extract in standard medium were used as the experimental group. Following the ingestion of the various toxic compounds, the survival rate of the flies was determined. Cell viability and levels of reactive oxygen species (ROS) were detected using 7‑amino‑actinomycin D and dihydroethidium staining, respectively. The present study demonstrated that aqueous extracts of C. sativus L. may significantly increase the lifespan and survival rate of adult flies. Additionally, C. sativus L. may decrease epithelial cell death and ROS levels, resulting in improved intestinal morphology. These findings indicated that C. sativus L. had a protective effect against intestinal injury and may extend the lifespan of Drosophila. Therefore, the findings of the present study may improve the understanding of clinical researchers on the complex effects of C. sativus L. in intestinal disorders.

  19. An optimal inventory policy under certainty distributed demand for cutting tools with stochastically distributed lifespan

    Directory of Open Access Journals (Sweden)

    Cun Rong Li

    2015-12-01

    Full Text Available Traditional inventory policy was deeply investigated for various kinds of demand in different industrial sectors. More extensive explorations on inventory policy, including the combination with manufacturing process, detailed attributes of the purchased products, etc. was conducted by many researchers. During manufacturing process, lifespan of cutting tools have significant impact on both the quantity of inventory and production cost. In this paper, the impact of maximum allowable stopping time for cutting tools on production-inventory policy under general production demands was investigated. An optimal inventory policy with general demand (OIPGD was developed with which the allowable stopping time for tools, order-up-to-level inventory, and order cycle can be optimally determined by an exhaustive searching algorithm. Examples with different distributions on tool lifespan and production demand is presented to show the implementation of the OIPGD model. The results and the sensitivity analysis about the parameters show that optimized combination of selection for tool allowable stopping time, order-up-to-level, and order cycle time can dramatically minimize the total cost of the whole inventory activity.

  20. Conditional abrogation of Atm in osteoclasts extends osteoclast lifespan and results in reduced bone mass.

    Science.gov (United States)

    Hirozane, Toru; Tohmonda, Takahide; Yoda, Masaki; Shimoda, Masayuki; Kanai, Yae; Matsumoto, Morio; Morioka, Hideo; Nakamura, Masaya; Horiuchi, Keisuke

    2016-09-28

    Ataxia-telangiectasia mutated (ATM) kinase is a central component involved in the signal transduction of the DNA damage response (DDR) and thus plays a critical role in the maintenance of genomic integrity. Although the primary functions of ATM are associated with the DDR, emerging data suggest that ATM has many additional roles that are not directly related to the DDR, including the regulation of oxidative stress signaling, insulin sensitivity, mitochondrial homeostasis, and lymphocyte development. Patients and mice lacking ATM exhibit growth retardation and lower bone mass; however, the mechanisms underlying the skeletal defects are not fully understood. In the present study, we generated mutant mice in which ATM is specifically inactivated in osteoclasts. The mutant mice did not exhibit apparent developmental defects but showed reduced bone mass due to increased osteoclastic bone resorption. Osteoclasts lacking ATM were more resistant to apoptosis and showed a prolonged lifespan compared to the controls. Notably, the inactivation of ATM in osteoclasts resulted in enhanced NF-κB signaling and an increase in the expression of NF-κB-targeted genes. The present study reveals a novel function for ATM in regulating bone metabolism by suppressing the lifespan of osteoclasts and osteoclast-mediated bone resorption.

  1. Immunomodulation by classical conditioning in NZB/W (F1) mice: Lifespan and diurnal variation

    Science.gov (United States)

    Miguel, Mario André Leocadio; Menna-Barreto, Luiz

    2016-01-01

    Systemic Lupus Eritematosus (SLE) is a systemic inflammatory disease often treated with the agent cyclophosphamide (CY), known by provoking important adverse reactions to the organism. Ader and Cohen have demonstrated an alternative way of administrating this agent based on pavlovian conditioning, in order to reduce the aggression caused by CY. Considering the influence of the temporal organization on learning and memory processes, the purpose of this study was to understand the temporal aspects involved in the conditioned immunomodulation. In a search for circadian modulation, we selected NZB/W (F1) female mice, a strain that spontaneously develop SLE. Divided into two major groups, the animals were submitted, in different phases of day, to a classical conditioning immunomodulation protocol, consisting in weekly parings of saccharin solution and CY injections. The success of the paradigm was evaluated by comparing lifespan among the groups. Simultaneously, it was monitored the water intake behavior, in order to correlate the stability of two rhythmic parameters, amplitude and spectral power density of the 24-h rhythm, with the progression of SLE. Our results indicate that mice could benefit from the conditioning task performed either in the light phase or in the dark phase of the LD cycle, as expressed by an increased lifespan. Concerning the rhythmic parameters, there was evidence of association between the rhythmic stability and the evolution of SLE, demonstrated by the maintenance of healthy levels of amplitude and spectral potency of the 24-h rhythm in animals exposed to the conditioning paradigm. PMID:27226820

  2. Sensitivity of primary fibroblasts in culture to atmospheric oxygen does not correlate with species lifespan

    Science.gov (United States)

    Patrick, Alison; Seluanov, Michael; Hwang, Chaewon; Tam, Jonathan; Khan, Tanya; Morgenstern, Ari; Wiener, Lauren; Vazquez, Juan M.; Zafar, Hiba; Wen, Robert; Muratkalyeva, Malika; Doerig, Katherine; Zagorulya, Maria; Cole, Lauren; Catalano, Sophia; Lobo Ladd, Aliny AB; Coppi, A. Augusto; Coşkun, Yüksel; Tian, Xiao; Ablaeva, Julia; Nevo, Eviatar; Gladyshev, Vadim N.; Zhang, Zhengdong D.; Vijg, Jan; Seluanov, Andrei; Gorbunova, Vera

    2016-01-01

    Differences in the way human and mouse fibroblasts experience senescence in culture had long puzzled researchers. While senescence of human cells is mediated by telomere shortening, Parrinello et al. demonstrated that senescence of mouse cells is caused by extreme oxygen sensitivity. It was hypothesized that the striking difference in oxygen sensitivity between mouse and human cells explains their different rates of aging. To test if this hypothesis is broadly applicable, we cultured cells from 16 rodent species with diverse lifespans in 3% and 21% oxygen and compared their growth rates. Unexpectedly, fibroblasts derived from laboratory mouse strains were the only cells demonstrating extreme sensitivity to oxygen. Cells from hamster, muskrat, woodchuck, capybara, blind mole rat, paca, squirrel, beaver, naked mole rat and wild-caught mice were mildly sensitive to oxygen, while cells from rat, gerbil, deer mouse, chipmunk, guinea pig and chinchilla showed no difference in the growth rate between 3% and 21% oxygen. We conclude that, although the growth of primary fibroblasts is generally improved by maintaining cells in 3% oxygen, the extreme oxygen sensitivity is a peculiarity of laboratory mouse strains, possibly related to their very long telomeres, and fibroblast oxygen sensitivity does not directly correlate with species' lifespan. PMID:27163160

  3. Life-span development of self-esteem and its effects on important life outcomes.

    Science.gov (United States)

    Orth, Ulrich; Robins, Richard W; Widaman, Keith F

    2012-06-01

    We examined the life-span development of self-esteem and tested whether self-esteem influences the development of important life outcomes, including relationship satisfaction, job satisfaction, occupational status, salary, positive and negative affect, depression, and physical health. Data came from the Longitudinal Study of Generations. Analyses were based on 5 assessments across a 12-year period of a sample of 1,824 individuals ages 16 to 97 years. First, growth curve analyses indicated that self-esteem increases from adolescence to middle adulthood, reaches a peak at about age 50 years, and then decreases in old age. Second, cross-lagged regression analyses indicated that self-esteem is best modeled as a cause rather than a consequence of life outcomes. Third, growth curve analyses, with self-esteem as a time-varying covariate, suggested that self-esteem has medium-sized effects on life-span trajectories of affect and depression, small to medium-sized effects on trajectories of relationship and job satisfaction, a very small effect on the trajectory of health, and no effect on the trajectory of occupational status. These findings replicated across 4 generations of participants--children, parents, grandparents, and their great-grandparents. Together, the results suggest that self-esteem has a significant prospective impact on real-world life experiences and that high and low self-esteem are not mere epiphenomena of success and failure in important life domains. 2012 APA, all rights reserved

  4. SIRT1 in the brain—connections with aging-associated disorders and lifespan

    Science.gov (United States)

    Ng, Fanny; Wijaya, Laura; Tang, Bor Luen

    2015-01-01

    The silent mating type information regulation 2 proteins (sirtuins) 1 of class III histone deacetylases (HDACs) have been associated with health span and longevity. SIRT1, the best studied member of the mammalian sirtuins, has a myriad of roles in multiple tissues and organs. However, a significant part of SIRT1’s role that impinges on aging and lifespan may lie in its activities in the central nervous system (CNS) neurons. Systemically, SIRT1 influences energy metabolism and circadian rhythm through its activity in the hypothalamic nuclei. From a cell biological perspective, SIRT1 is a crucial component of multiple interconnected regulatory networks that modulate dendritic and axonal growth, as well as survival against stress. This neuronal cell autonomous activity of SIRT1 is also important for neuronal plasticity, cognitive functions, as well as protection against aging-associated neuronal degeneration and cognitive decline. We discuss recent findings that have shed light on the various activities of SIRT1 in the brain, which collectively impinge on aging-associated disorders and lifespan. PMID:25805970

  5. SIRT1 in the Brain – Connections with Aging-associated Disorders and Lifespan

    Directory of Open Access Journals (Sweden)

    Fanny eNg

    2015-03-01

    Full Text Available The silent mating type information regulation 2 proteins (sirtuins 1 of class III histone deacetylases have been associated with health span and longevity. SIRT1, the best studied member of the mammalian sirtuins, has a myriad of roles in multiple tissues and organs. However, a significant part of SIRT1’s role that impinges on aging and lifespan may lie in its activities in the central nervous system (CNS neurons. Systemically, SIRT1 influences energy metabolism and circadian rhythm through its activity in the hypothalamic nuclei. From a cell biological perspective, SIRT1 is a crucial component of multiple interconnected regulatory networks that modulate dendritic and axonal growth, as well as survival against stress. This neuronal cell autonomous activity of SIRT1 is also important for neuronal plasticity, cognitive functions, as well as protection against aging-associated neuronal degeneration and cognitive decline. We discuss recent findings that have shed light on the various activities of SIRT1 in the brain, which collectively impinge on aging-associated disorders and lifespan.

  6. Extension of Drosophila lifespan by Rosa damascena associated with an increased sensitivity to heat.

    Science.gov (United States)

    Schriner, Samuel E; Katoozi, Niki S; Pham, Kevin Q; Gazarian, Maral; Zarban, Asghar; Jafari, Mahtab

    2012-04-01

    Rosa damascena, or Damask rose, is a rose hybrid commonly harvested for rose oil used in perfumery and for rose water used to flavor food. The petal extract of R. damascena was recently found to decrease Drosophila melanogaster mortality without impairing reproductive fitness or metabolic rate. Here, we report that R. damascena extended both mean and maximum lifespan of the fly. The extract also protected against oxidative stress in flies, predominantly in females. However, it did not alter mitochondrial respiration or content, superoxide production, or the major antioxidant defenses, superoxide dismutase and catalase. The extract increased survival in both sexes when exposed to reduced iron, though surprisingly, it sensitized both sexes to heat stress (survival at 37°C), and appeared to down-regulate the major heat shock protein HSP70 and the small mitochondrial heat shock protein HSP22, at 25°C and after heat shock (4 h at 37°C). We hypothesize that R. damascena extends lifespan by protecting against iron, which concomitantly leads to decreased HSP expression and compromising heat tolerance.

  7. Korean mistletoe (Viscum album coloratum) extract extends the lifespan of nematodes and fruit flies.

    Science.gov (United States)

    Lee, Shin-Hae; An, Hyo-Sun; Jung, Yong Woo; Lee, Eun-Ji; Lee, Hye-Yeon; Choi, Eun-Seok; An, Seon Woo; Son, Heehwa; Lee, Seung-Jae; Kim, Jong-Bae; Min, Kyung-Jin

    2014-04-01

    Viscum album coloratum (Korean mistletoe) is a semi-parasitic plant that grows on various trees and has a variety of biological functions such as immunomodulation, apoptosis, and anti-tumor activity. In this study, we investigated the effects of Korean mistletoe extract (KME) on lifespan in experimental models using Caenorhabditis elegans and Drosophila melanogaster. Supplementation of KME at 50 μg/ml extended the mean survival time by 9.61 and 19.86 % in worms and flies, respectively. The longevity benefit of KME was not due to reduced feeding, reproduction, and/or locomotion in flies and worms. The supplementation of KME also did not increase resistance to various stresses including heat shock, oxidative, or starvation stresses. Furthermore, KME did not further extend the lifespan of flies fed a dietary restricted diet but did increase the expression of Sir2, one of the target genes of dietary restriction, suggesting that KME may function as a putative dietary restriction mimetic. These results also suggest that the longevity promoting effects of KME may be an example of mild stress-induced hormesis.

  8. Short-term memory predictions across the lifespan: monitoring span before and after conducting a task.

    Science.gov (United States)

    Bertrand, Julie Marilyne; Moulin, Chris John Anthony; Souchay, Céline

    2017-05-01

    Our objective was to explore metamemory in short-term memory across the lifespan. Five age groups participated in this study: 3 groups of children (4-13 years old), and younger and older adults. We used a three-phase task: prediction-span-postdiction. For prediction and postdiction phases, participants reported with a Yes/No response if they could recall in order a series of images. For the span task, they had to actually recall such series. From 4 years old, children have some ability to monitor their short-term memory and are able to adjust their prediction after experiencing the task. However, accuracy still improves significantly until adolescence. Although the older adults had a lower span, they were as accurate as young adults in their evaluation, suggesting that metamemory is unimpaired for short-term memory tasks in older adults. •We investigate metamemory for short-term memory tasks across the lifespan. •We find younger children cannot accurately predict their span length. •Older adults are accurate in predicting their span length. •People's metamemory accuracy was related to their short-term memory span.

  9. Brain structure across the lifespan: the influence of stress and mood

    Directory of Open Access Journals (Sweden)

    Jose Miguel Soares

    2014-11-01

    Full Text Available Normal brain aging is an inevitable and heterogeneous process characterized by a selective pattern of structural changes. Such heterogeneity arises as a consequence of cumulative effects over the lifespan, including stress and mood effects, which drive different micro- and macro-structural alterations in the brain. Investigating these differences in healthy age-related changes is a major challenge for the comprehension of the cognitive status. Herein we addressed the impact of normal aging, stress, mood and their interplay in the brain gray and white matter structure. We showed the critical impact of age in the white matter volume and how stress and mood influence brain volumetry across the lifespan. Moreover, we found a more profound effect of the interaction of aging/stress/mood on structures located in the left hemisphere. These findings help to clarify some divergent results associated with the aging decline and to enlighten the association between abnormal volumetric alterations and several states that may lead to psychiatric disorders.

  10. Beat Synchronization across the Lifespan: Intersection of Development and Musical Experience.

    Science.gov (United States)

    Thompson, Elaine C; White-Schwoch, Travis; Tierney, Adam; Kraus, Nina

    2015-01-01

    Rhythmic entrainment, or beat synchronization, provides an opportunity to understand how multiple systems operate together to integrate sensory-motor information. Also, synchronization is an essential component of musical performance that may be enhanced through musical training. Investigations of rhythmic entrainment have revealed a developmental trajectory across the lifespan, showing synchronization improves with age and musical experience. Here, we explore the development and maintenance of synchronization in childhood through older adulthood in a large cohort of participants (N = 145), and also ask how it may be altered by musical experience. We employed a uniform assessment of beat synchronization for all participants and compared performance developmentally and between individuals with and without musical experience. We show that the ability to consistently tap along to a beat improves with age into adulthood, yet in older adulthood tapping performance becomes more variable. Also, from childhood into young adulthood, individuals are able to tap increasingly close to the beat (i.e., asynchronies decline with age), however, this trend reverses from younger into older adulthood. There is a positive association between proportion of life spent playing music and tapping performance, which suggests a link between musical experience and auditory-motor integration. These results are broadly consistent with previous investigations into the development of beat synchronization across the lifespan, and thus complement existing studies and present new insights offered by a different, large cross-sectional sample.

  11. Positive effect of porphyrans on the lifespan and vitality of Drosophila melanogaster

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The effects of degraded porphyran (P1) and natural porphyran (P) on the lifespan and vitality of Drosophila melanogaster are studied. The porphyrans, added daily to the food medium at 0.2% and 1% concentrations, can significantly increase the lifespan in average of 55.79 and 58.23 d in 0.2% P1 diet females and 1% P1 diet_males, extending by 12.29% and 8.60% over the corresponding controls,respectively. The effects of porphyrans on D. melanogaster in heat-stress condition were also examined,and found a remarkable increase in survival time. The results which are consistently associated with the use of porphyrans are related to their free radical scavenger action. Considerable increase in vitality demonstrated that vitalities of middle-aged fly (assessed by measuring their mating capacity) was observed after porphyrans addition. Therefore, porphyrans are effective in reducing the rate of aging, and P1 in low molecular weight is better than natural P.

  12. The SAGA Histone Deubiquitinase Module Controls Yeast Replicative Lifespan via Sir2 Interaction

    Directory of Open Access Journals (Sweden)

    Mark A. McCormick

    2014-07-01

    Full Text Available We have analyzed the yeast replicative lifespan of a large number of open reading frame (ORF deletions. Here, we report that strains lacking genes SGF73, SGF11, and UBP8 encoding SAGA/SLIK complex histone deubiquitinase module (DUBm components are exceptionally long lived. Strains lacking other SAGA/SALSA components, including the acetyltransferase encoded by GCN5, are not long lived; however, these genes are required for the lifespan extension observed in DUBm deletions. Moreover, the SIR2-encoded histone deacetylase is required, and we document both a genetic and physical interaction between DUBm and Sir2. A series of studies assessing Sir2-dependent functions lead us to propose that DUBm strains are exceptionally long lived because they promote multiple prolongevity events, including reduced rDNA recombination and altered silencing of telomere-proximal genes. Given that ataxin-7, the human Sgf73 ortholog, causes the neurodegenerative disease spinocerebellar ataxia type 7, our findings indicate that the genetic and epigenetic interactions between DUBm and SIR2 will be relevant to neurodegeneration and aging.

  13. Mitochondrial electron transport chain dysfunction during development does not extend lifespan in Drosophila melanogaster.

    Science.gov (United States)

    Rera, Michael; Monnier, Véronique; Tricoire, Hervé

    2010-02-01

    Since the initial identification of reactive oxygen species (ROS) as the major factor in aging, many studies have provided evidence for the central role of mitochondria in longevity. A few years ago, an unexpected finding showed that the inactivation of the mitochondrial respiratory chain (MRC) in Caenorhabditis elegans, during the developmental stages only, extended lifespan. Activation of this mitochondrial pathway affecting aging (MIT) is associated with several phenotypic features: increased longevity, increased time of development, decreased fertility/fecundity and reduced adult size. Here, we investigated this pathway in another model organism, Drosophila melanogaster. To assess the role of mitochondrial activity in the Drosophila aging process, we partially inactivated the MRC using RNA interference (RNAi) during larval stages. Developmental perturbation of the respiratory process prolonged development, increased lethality during developmental stage, reduced both fecundity and fertility and slightly reduced individual weight. However, in contrast to the nematode, this genetic intervention either shortened or had no effect on lifespan, depending on the level of gene inactivation. Thus, the effects of MRC disruption during development on aging differ between species. We discuss the possible origins of such differences.

  14. Patterns of philopatry and longevity contribute to the evolution of post-reproductive lifespan in mammals.

    Science.gov (United States)

    Nichols, H J; Zecherle, L; Arbuckle, K

    2016-02-01

    While menopause has long been known as a characteristic trait of human reproduction, evidence for post-reproductive lifespan (PRLS) has recently been found in other mammals. Adaptive and non-adaptive hypotheses have been proposed to explain the evolution of PRLS, but formal tests of these are rare. We use a phylogenetic approach to evaluate hypotheses for the evolution of PRLS among mammals. In contrast to theoretical models predicting that PRLS may be promoted by male philopatry (which increases relatedness between a female and her group in old age), we find little evidence that male philopatry led to the evolution of a post-reproductive period. However, the proportion of life spent post-reproductive was related to lifespan and patterns of philopatry, suggesting that the duration of PRLS may be impacted by both non-adaptive and adaptive processes. Finally, the proportion of females experiencing PRLS was higher in species with male philopaty and larger groups, in accordance with adaptive models of PRLS. We suggest that the origin of PRLS primarily follows the non-adaptive 'mismatch' scenario, but that patterns of philopatry may subsequently confer adaptive benefits of late-life helping. © 2016 The Authors.

  15. The lifespan of 3D radial solutions to the non-isentropic relativistic Euler equations

    Science.gov (United States)

    Wei, Changhua

    2017-10-01

    This paper investigates the lower bound of the lifespan of three-dimensional spherically symmetric solutions to the non-isentropic relativistic Euler equations, when the initial data are prescribed as a small perturbation with compact support to a constant state. Based on the structure of the hyperbolic system, we show the almost global existence of the smooth solutions to Eulerian flows (polytropic gases and generalized Chaplygin gases) with genuinely nonlinear characteristics. While for the Eulerian flows (Chaplygin gas and stiff matter) with mild linearly degenerate characteristics, we show the global existence of the radial solutions, moreover, for the non-strictly hyperbolic system (pressureless perfect fluid) satisfying the mild linearly degenerate condition, we prove the blowup phenomenon of the radial solutions and show that the lifespan of the solutions is of order O(ɛ ^{-1}), where ɛ denotes the width of the perturbation. This work can be seen as a complement of our work (Lei and Wei in Math Ann 367:1363-1401, 2017) for relativistic Chaplygin gas and can also be seen as a generalization of the classical Eulerian fluids (Godin in Arch Ration Mech Anal 177:497-511, 2005, J Math Pures Appl 87:91-117, 2007) to the relativistic Eulerian fluids.

  16. The effects of oral clefts on hospital use throughout the lifespan

    Directory of Open Access Journals (Sweden)

    Wehby George L

    2012-03-01

    Full Text Available Abstract Background Oral clefts are one of the most common birth defects worldwide. They require multiple healthcare interventions and add significant burden on the health and quality of life of affected individuals. However, not much is known about the long term effects of oral clefts on health and healthcare use of affected individuals. In this study, we evaluate the effects of oral clefts on hospital use throughout the lifespan. Methods We estimate two-part regression models for hospital admission and length of stay for several age groups up to 68 years of age. The study employs unique secondary population-based data from several administrative inpatient, civil registration, demographic and labor market databases for 7,670 individuals born with oral clefts between 1936 and 2002 in Denmark, and 220,113 individuals without oral clefts from a 5% random sample of the total birth population from 1936 to 2002. Results Oral clefts significantly increase hospital use for most ages below 60 years by up to 233% for children ages 0-10 years and 16% for middle age adults. The more severe cleft forms (cleft lip with palate have significantly larger effects on hospitalizations than less severe forms. Conclusions The results suggest that individuals with oral clefts have higher hospitalization risks than the general population throughout most of the lifespan.

  17. Logic and belief across the lifespan: the rise and fall of belief inhibition during syllogistic reasoning.

    Science.gov (United States)

    De Neys, Wim; Van Gelder, Elke

    2009-01-01

    Popular reasoning theories postulate that the ability to inhibit inappropriate beliefs lies at the heart of the human reasoning engine. Given that people's inhibitory capacities are known to rise and fall across the lifespan, we predicted that people's deductive reasoning performance would show similar curvilinear age trends. A group of children (12-year-olds), young adults (20-year-olds), and older adults (65+-year-olds) were presented with a classic syllogistic reasoning task and a decision-making questionnaire. Results indicated that on syllogisms where beliefs and logic conflicted, reasoning performance showed the expected curvilinear age trend: Reasoning performance initially increased from childhood to early adulthood but declined again in later life. On syllogisms where beliefs and logic were consistent and sound reasoning did not require belief inhibition, however, age did not affect performance. Furthermore, across the lifespan we observed that the better people were at resisting intuitive temptations in the decision-making task, the less they were biased by their beliefs on the conflict syllogisms. As with the effect of age, one's ability to override intuitions in the decision-making task did not mediate reasoning performance on the no-conflict syllogisms. Results lend credence to the postulated central role of inhibitory processing in those situations where beliefs and logic conflict.

  18. Staphylococcus saprophyticus surface-associated protein (Ssp) is associated with lifespan reduction in Caenorhabditis elegans.

    Science.gov (United States)

    Szabados, Florian; Mohner, Amelie; Kleine, Britta; Gatermann, Sören G

    2013-10-01

    Staphylococcal lipases have been proposed as pathogenicity factors. In Staphylococcus saprophyticus the surface-associated protein (Ssp) has been previously characterized as a cell wall-associated true lipase. A S. saprophyticus Δssp::ermB mutant has been described as less virulent in an in vivo model of urinary tract infection compared with its wild-type. This is the first report showing that S. saprophyticus induced a lifespan reduction in Caenorhabditis elegans similar to that of S. aureus RN4220. In two S. saprophyticus Δssp::ermB mutants lifespan reduction in C. elegans was partly abolished. In order to attribute virulence to the lipase activity itself and distinguish this phenomenon from the presence of the Ssp-protein, the conserved active site of the lipase was modified by site-directed ligase-independent mutagenesis and lipase activity-deficient mutants were constructed. These results indicate that the Ssp is associated with pathogenicity in C. elegans and one could speculate that the lipase activity itself is responsible for this virulence.

  19. The influence of executive functions on spatial biases varies during the lifespan

    Directory of Open Access Journals (Sweden)

    Fiia Takio

    2014-10-01

    Full Text Available Many perceptual processes, such as language or face perception, are asymmetrically organised in the hemispheres already in childhood. These asymmetries induce behaviourally observable spatial biases in which the observer perceives stimuli in one of the hemispaces more efficiently or more frequently than in the other one. Another source for spatial biases is spatial attention which is also asymmetrically organised in the hemispheres. The bias induced by attention is directed towards the right side, which is clearly demonstrated by patients with neglect but also in lesser degree by healthy observers in cognitively loading situations. Recent findings indicate that children and older adults show stronger spatial biases than young adults. We discuss how the development of executive functions might contribute to the manifestation of spatial biases during the lifespan. We present a model in which the interaction between the asymmetrical perceptual processes, the age-related development of the lateralised spatial attention and the development of the executive functions influence spatial perceptual performance and in which the development and decline of the executive processes during the lifespan modify the spatial biases.

  20. Lifespan and Aggregate Size Variables in Specifications of Mortality or Survivorship

    Science.gov (United States)

    Epelbaum, Michael

    2014-01-01

    A specification of mortality or survivorship provides respective explicit details about mortality's or survivorship's relationships with one or more other variables (e.g., age, sex, etc.). Previous studies have discovered and analyzed diverse specifications of mortality or survivorship; these discoveries and analyses suggest that additional specifications of mortality or survivorship have yet to be discovered and analyzed. In consistency with previous research, multivariable limited powered polynomials regression analyses of mortality and survivorship of selected humans (Swedes, 1760–2008) and selected insects (caged medflies) show age-specific, historical-time-specific, environmental-context-specific, and sex-specific mortality and survivorship. These analyses also present discoveries of hitherto unknown lifespan-specific, contemporary-aggregate-size-specific, and lifespan-aggregate-size-specific mortality and survivorship. The results of this investigation and results of previous research help identify variables for inclusion in regression models of mortality or survivorship. Moreover, these results and results of previous research strengthen the suggestion that additional specifications of mortality or survivorship have yet to be discovered and analyzed, and they also suggest that specifications of mortality and survivorship indicate corresponding specifications of frailty and vitality. Furthermore, the present analyses reveal the usefulness of a multivariable limited powered polynomials regression model-building approach. This article shows that much has yet to be learned about specifications of mortality or survivorship of diverse kinds of individuals in diverse times and places. PMID:24454719

  1. Birth mass is the key to understanding the negative correlation between lifespan and body size in dogs.

    Science.gov (United States)

    Fan, Rong; Olbricht, Gayla; Baker, Xavior; Hou, Chen

    2016-12-08

    Larger dog breeds live shorter than the smaller ones, opposite of the mass-lifespan relationship observed across mammalian species. Here we use data from 90 dog breeds and a theoretical model based on the first principles of energy conservation and life history tradeoffs to explain the negative correlation between longevity and body size in dogs. We found that the birth/adult mass ratio of dogs scales negatively with adult size, which is different than the weak interspecific scaling in mammals. Using the model, we show that this ratio, as an index of energy required for growth, is the key to understanding why the lifespan of dogs scales negatively with body size. The model also predicts that the difference in mass-specific lifetime metabolic energy usage between dog breeds is proportional to the difference in birth/adult mass ratio. Empirical data on lifespan, body mass, and metabolic scaling law of dogs strongly supports this prediction.

  2. miR-124/ATF-6, a novel lifespan extension pathway of Astragalus polysaccharide in Caenorhabditis elegans.

    Science.gov (United States)

    Wang, Ning; Liu, Jing; Xie, Fang; Gao, Xu; Ye, Jian-Han; Sun, Lu-Yao; Wei, Ran; Ai, Jing

    2015-02-01

    MicroRNAs (miRNAs), especially evolutionarily conserved miRNAs play critical roles in regulating various biological process. However, the functions of conserved miRNAs in longevity are still largely unknown. Astragalus polysaccharide (APS) was recently shown to extend lifespan of Caenorhabditis elegans, but its molecular mechanisms have not been fully understood. In the present study, we characterize that microRNA mediated a novel longevity pathway of APS in C. elegans. We found that APS markedly extended the lifespan of C. elegans at the second and the fourth stages. A highly conserved miRNA miR-124 was significantly upregulated in APS-treated C. elegans. Overexpression miR-124 caused the lifespan extension of C. elegans and vice versa, indicating miR-124 regulates the longevity of C. elegans. Using luciferase assay, atf-6 was established as a target gene of miR-124 which acting on three binding sites at atf-6 3'UTR. Consistently, agomir-cel-miR-124 was also shown to inhibit ATF-6 expression in C. elegans. APS-treated C. elegans showed the down-regulation of atf-6 at protein level. Furthermore, the knockdown of atf-6 by RNAi extended the lifespan of C. elegans, indicating atf-6 regulated by miR-124 contributes to lifespan extension. Taken together, miR-124 regulating ATF-6 is a new potential longevity signal pathway, which underlies the lifespan-extending effects of APS in C. elegans. © 2014 Wiley Periodicals, Inc.

  3. Cellular bioluminescence imaging.

    Science.gov (United States)

    Welsh, David K; Noguchi, Takako

    2012-08-01

    Bioluminescence imaging of live cells has recently been recognized as an important alternative to fluorescence imaging. Fluorescent probes are much brighter than bioluminescent probes (luciferase enzymes) and, therefore, provide much better spatial and temporal resolution and much better contrast for delineating cell structure. However, with bioluminescence imaging there is virtually no background or toxicity. As a result, bioluminescence can be superior to fluorescence for detecting and quantifying molecules and their interactions in living cells, particularly in long-term studies. Structurally diverse luciferases from beetle and marine species have been used for a wide variety of applications, including tracking cells in vivo, detecting protein-protein interactions, measuring levels of calcium and other signaling molecules, detecting protease activity, and reporting circadian clock gene expression. Such applications can be optimized by the use of brighter and variously colored luciferases, brighter microscope optics, and ultrasensitive, low-noise cameras. This article presents a review of how bioluminescence differs from fluorescence, its applications to cellular imaging, and available probes, optics, and detectors. It also gives practical suggestions for optimal bioluminescence imaging of single cells.

  4. Cellular neurothekeoma with melanocytosis.

    Science.gov (United States)

    Wu, Ren-Chin; Hsieh, Yi-Yueh; Chang, Yi-Chin; Kuo, Tseng-Tong

    2008-02-01

    Cellular neurothekeoma (CNT) is a benign dermal tumor mainly affecting the head and neck and the upper extremities. It is characterized histologically by interconnecting fascicles of plump spindle or epithelioid cells with ample cytoplasm infiltrating in the reticular dermis. The histogenesis of CNT has been controversial, although it is generally regarded as an immature counterpart of classic/myxoid neurothekeoma, a tumor with nerve sheath differentiation. Two rare cases of CNT containing melanin-laden cells were described. Immunohistochemical study with NKI/C3, vimentin, epithelial membrane antigen, smooth muscle antigen, CD34, factor XIIIa, collagen type IV, S100 protein and HMB-45 was performed. Both cases showed typical growth pattern of CNT with interconnecting fascicles of epithelioid cells infiltrating in collagenous stroma. One of the nodules contained areas exhibiting atypical cytological features. Melanin-laden epithelioid or dendritic cells were diffusely scattered throughout one nodule, and focally present in the peripheral portion of the other nodule. Both nodules were strongly immunoreactive to NKI/C3 and vimentin, but negative to all the other markers employed. CNT harboring melanin-laden cells may pose diagnostic problems because of their close resemblance to nevomelanocytic lesions and other dermal mesenchymal tumors. These peculiar cases may also provide further clues to the histogenesis of CNT.

  5. Regulation of cellular senescence by the essential caveolar component PTRF/Cavin-1

    Institute of Scientific and Technical Information of China (English)

    Lin Bai; Xiaoli Deng; Juanjuan Li; Miao Wang; Qian Li; Wei An; Deli A; Yu-Sheng Cong

    2011-01-01

    Polymerase I and transcript release factor (PTRF, also known as Cavin-1) is an essential component in the biogenesis and function of caveolae. Here, we show that PTRF expression is increased in senescent human fibroblasts.Importantly, overexpression of PTRF induced features characteristic of cellular senescence, whereas reduced PTRF expression extended the cellular replicative lifespan. Interestingly, we found that PTRF localized primarily to the nuclei of young and quiescent WI-38 human fibroblasts, but translocated to the cytosol and plasma membrane during cellular senescence. Furthermore, electron microscopic analysis demonstrated an increased number of caveolar structures in senescent and PTRF-transfected WI-38 cells. Our data suggest that the role of PTRF in cellular senes cence is dependent on its targeting to caveolae and its interaction with caveolin-l, which appeared to be regulated by the phosphorylation of PTRF. Taken together, our findings identify PTRF as a novel regulator of cellular senescence that acts through the p53/p21 and caveolar pathways.

  6. Discussion of Teaching of Human Lifespan Development%人体发育学教学实践探讨

    Institute of Scientific and Technical Information of China (English)

    赵杰; 李卫东; 李国标; 陈洁

    2014-01-01

    人体发育学是康复治疗学专业的一门专业基础课。本文对人体发育学的课程内容、教学方法、考试模式3个方面进行探讨。%Human lifespan development is a basic course of the specialty of rehabilitation therapy. This paper discussed the teaching of human lifespan development in sections of course content, teaching methods and examination pattern.

  7. Acacetin 7-O-α-l-rhamnopyranosyl (1-2) β-D-xylopyranoside Elicits Life-span Extension and Stress Resistance in Caenorhabditis elegans.

    Science.gov (United States)

    Asthana, Jyotsna; Yadav, Deepti; Pant, Aakanksha; Yadav, A K; Gupta, M M; Pandey, Rakesh

    2016-09-01

    The advancements in the field of gerontology have unraveled the signaling pathways that regulate life span, suggesting that it might be feasible to modulate aging. To this end, we isolated a novel phytomolecule Acacetin 7-O-α-l-rhamnopyranosyl (1-2) β-D-xylopyranoside (ARX) from Premna integrifolia and evaluated its antiaging effects in Caenorhabditis elegans The spectral data analysis revealed the occurrence of a new compound ARX. Out of the three tested pharmacological doses of ARX, viz. 5, 25, and 50 µM, the 25-µM dose was able to extend life span in C. elegans by more than 39%. The present study suggests that ARX affects bacterial metabolism, which in turn leads to dietary restriction (DR)-like effects in the worms. The effect of ARX on worms with mutations (mev-1, eat-2, sir-2.1, skn-1, daf-16, and hsf-1) indicates that ARX-mediated life-span extension involves mechanisms associated with DR and maintenance of cellular redox homeostasis. This study is the first time report on longevity-promoting activity of ARX in C. elegans mediated by stress and DR-regulating genes. This novel phytomolecule can contribute in designing therapeutics for managing aging and age-related diseases.

  8. SIRT1 overexpression antagonizes cellular senescence with activated ERK/S6k1 signaling in human diploid fibroblasts.

    Directory of Open Access Journals (Sweden)

    Jing Huang

    Full Text Available Sir2, a NAD-dependent deacetylase, modulates lifespan in yeasts, worms and flies. The SIRT1, mammalian homologue of Sir2, regulates signaling for favoring survival in stress. But whether SIRT1 has the function to influence cell viability and senescence under non-stressed conditions in human diploid fibroblasts is far from unknown. Our data showed that enforced SIRT1 expression promoted cell proliferation and antagonized cellular senescence with the characteristic features of delayed Senescence-Associated beta-galactosidase (SA-beta-gal staining, reduced Senescence-Associated Heterochromatic Foci (SAHF formation and G1 phase arrest, increased cell growth rate and extended cellular lifespan in human fibroblasts, while dominant-negative SIRT1 allele (H363Y did not significantly affect cell growth and senescence but displayed a bit decreased lifespan. Western blot results showed that SIRT1 reduced the expression of p16(INK4A and promoted phosphorylation of Rb. Our data also exposed that overexpression of SIRT1 was accompanied by enhanced activation of ERK and S6K1 signaling. These effects were mimicked in both WI38 cells and 2BS cells by concentration-dependent resveratrol, a SIRT1 activator. It was noted that treatment of SIRT1-.transfected cells with Rapamycin, a mTOR inhibitor, reduced the phosphorylation of S6K1 and the expression of Id1, implying that SIRT1-induced phosphorylation of S6K1 may be partly for the decreased expression of p16(INK4A and promoted phosphorylation of Rb in 2BS. It was also observed that the expression of SIRT1 and phosphorylation of ERK and S6K1 was declined in senescent 2BS. These findings suggested that SIRT1-promoted cell proliferation and antagonized cellular senescence in human diploid fibroblasts may be, in part, via the activation of ERK/ S6K1 signaling.

  9. Reduced costs of reproduction in females mediate a shift from a male-biased to a female-biased lifespan in humans.

    Science.gov (United States)

    Bolund, Elisabeth; Lummaa, Virpi; Smith, Ken R; Hanson, Heidi A; Maklakov, Alexei A

    2016-04-18

    The causes underlying sex differences in lifespan are strongly debated. While females commonly outlive males in humans, this is generally less pronounced in societies before the demographic transition to low mortality and fertility rates. Life-history theory suggests that reduced reproduction should benefit female lifespan when females pay higher costs of reproduction than males. Using unique longitudinal demographic records on 140,600 reproducing individuals from the Utah Population Database, we demonstrate a shift from male-biased to female-biased adult lifespans in individuals born before versus during the demographic transition. Only women paid a cost of reproduction in terms of shortened post-reproductive lifespan at high parities. Therefore, as fertility decreased over time, female lifespan increased, while male lifespan remained largely stable, supporting the theory that differential costs of reproduction in the two sexes result in the shifting patterns of sex differences in lifespan across human populations. Further, our results have important implications for demographic forecasts in human populations and advance our understanding of lifespan evolution.

  10. The presence of protective cytotoxic T lymphocytes does not correlate with shorter lifespans of productively infected cells in HIV-1 infection

    NARCIS (Netherlands)

    Spits, Hilde B; Mudrikova, Tania; Schellens, Ingrid M M; Wensing, Annemarie M J; Prins, Jan M; Feuth, Thijs; Spierings, Erik; Nijhuis, Monique; van Baarle, Debbie; Borghans, José A M

    2016-01-01

    OBJECTIVES AND DESIGN: CD8+ cytotoxic T lymphocytes (CTL) are important in the control of HIV infection. Although CTL are thought to reduce the lifespan of productively infected cells, CD8+ T-cell depletion in simian immunodeficiency virus-infected rhesus-macaques showed no effect on the lifespan of

  11. Development of Glutamatergic Proteins in Human Visual Cortex across the Lifespan.

    Science.gov (United States)

    Siu, Caitlin R; Beshara, Simon P; Jones, David G; Murphy, Kathryn M

    2017-06-21

    Traditionally, human primary visual cortex (V1) has been thought to mature within the first few years of life, based on anatomical studies of synapse formation, and establishment of intracortical and intercortical connections. Human vision, however, develops well beyond the first few years. Previously, we found prolonged development of some GABAergic proteins in human V1 (Pinto et al., 2010). Yet as >80% of synapses in V1 are excitatory, it remains unanswered whether the majority of synapses regulating experience-dependent plasticity and receptive field properties develop late, like their inhibitory counterparts. To address this question, we used Western blotting of postmortem tissue from human V1 (12 female, 18 male) covering a range of ages. Then we quantified a set of postsynaptic glutamatergic proteins (PSD-95, GluA2, GluN1, GluN2A, GluN2B), calculated indices for functional pairs that are developmentally regulated (GluA2:GluN1; GluN2A:GluN2B), and determined interindividual variability. We found early loss of GluN1, prolonged development of PSD-95 and GluA2 into late childhood, protracted development of GluN2A until ∼40 years, and dramatic loss of GluN2A in aging. The GluA2:GluN1 index switched at ∼1 year, but the GluN2A:GluN2B index continued to shift until ∼40 year before changing back to GluN2B in aging. We also identified young childhood as a stage of heightened interindividual variability. The changes show that human V1 develops gradually through a series of five orchestrated stages, making it likely that V1 participates in visual development and plasticity across the lifespan.SIGNIFICANCE STATEMENT Anatomical structure of human V1 appears to mature early, but vision changes across the lifespan. This discrepancy has fostered two hypotheses: either other aspects of V1 continue changing, or later changes in visual perception depend on extrastriate areas. Previously, we showed that some GABAergic synaptic proteins change across the lifespan, but most

  12. Free fall and cellular automata

    Directory of Open Access Journals (Sweden)

    Pablo Arrighi

    2016-03-01

    Full Text Available Three reasonable hypotheses lead to the thesis that physical phenomena can be described and simulated with cellular automata. In this work, we attempt to describe the motion of a particle upon which a constant force is applied, with a cellular automaton, in Newtonian physics, in Special Relativity, and in General Relativity. The results are very different for these three theories.

  13. About Strongly Universal Cellular Automata

    Directory of Open Access Journals (Sweden)

    Maurice Margenstern

    2013-09-01

    Full Text Available In this paper, we construct a strongly universal cellular automaton on the line with 11 states and the standard neighbourhood. We embed this construction into several tilings of the hyperbolic plane and of the hyperbolic 3D space giving rise to strongly universal cellular automata with 10 states.

  14. Reactive Programming of Cellular Automata

    OpenAIRE

    Boussinot, Frédéric

    2004-01-01

    Implementation of cellular automata using reactive programming gives a way to code cell behaviors in an abstract and modular way. Multiprocessing also becomes possible. The paper describes the implementation of cellular automata with the reactive programming language LOFT, a thread-based extension of C. Self replicating loops considered in artificial life are coded to show the interest of the approach.

  15. MIMO Communication for Cellular Networks

    CERN Document Server

    Huang, Howard; Venkatesan, Sivarama

    2012-01-01

    As the theoretical foundations of multiple-antenna techniques evolve and as these multiple-input multiple-output (MIMO) techniques become essential for providing high data rates in wireless systems, there is a growing need to understand the performance limits of MIMO in practical networks. To address this need, MIMO Communication for Cellular Networks presents a systematic description of MIMO technology classes and a framework for MIMO system design that takes into account the essential physical-layer features of practical cellular networks. In contrast to works that focus on the theoretical performance of abstract MIMO channels, MIMO Communication for Cellular Networks emphasizes the practical performance of realistic MIMO systems. A unified set of system simulation results highlights relative performance gains of different MIMO techniques and provides insights into how best to use multiple antennas in cellular networks under various conditions. MIMO Communication for Cellular Networks describes single-user,...

  16. Cellular automata analysis and applications

    CERN Document Server

    Hadeler, Karl-Peter

    2017-01-01

    This book focuses on a coherent representation of the main approaches to analyze the dynamics of cellular automata. Cellular automata are an inevitable tool in mathematical modeling. In contrast to classical modeling approaches as partial differential equations, cellular automata are straightforward to simulate but hard to analyze. In this book we present a review of approaches and theories that allow the reader to understand the behavior of cellular automata beyond simulations. The first part consists of an introduction of cellular automata on Cayley graphs, and their characterization via the fundamental Cutis-Hedlund-Lyndon theorems in the context of different topological concepts (Cantor, Besicovitch and Weyl topology). The second part focuses on classification results: What classification follows from topological concepts (Hurley classification), Lyapunov stability (Gilman classification), and the theory of formal languages and grammars (Kůrka classification). These classifications suggest to cluster cel...

  17. The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans

    Science.gov (United States)

    Apfeld, Javier; O'Connor, Greg; McDonagh, Tom; DiStefano, Peter S.; Curtis, Rory

    2004-01-01

    Although limiting energy availability extends lifespan in many organisms, it is not understood how lifespan is coupled to energy levels. We find that the AMP:ATP ratio, a measure of energy levels, increases with age in Caenorhabditis elegans and can be used to predict life expectancy. The C. elegans AMP-activated protein kinase α subunit AAK-2 is activated by AMP and functions to extend lifespan. In addition, either an environmental stressor that increases the AMP:ATP ratio or mutations that lower insulin-like signaling extend lifespan in an aak-2-dependent manner. Thus, AAK-2 is a sensor that couples lifespan to information about energy levels and insulin-like signals. PMID:15574588

  18. Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal.

    Science.gov (United States)

    Burkewitz, Kristopher; Morantte, Ianessa; Weir, Heather J M; Yeo, Robin; Zhang, Yue; Huynh, Frank K; Ilkayeva, Olga R; Hirschey, Matthew D; Grant, Ana R; Mair, William B

    2015-02-26

    Low energy states delay aging in multiple species, yet mechanisms coordinating energetics and longevity across tissues remain poorly defined. The conserved energy sensor AMP-activated protein kinase (AMPK) and its corresponding phosphatase calcineurin modulate longevity via the CREB regulated transcriptional coactivator (CRTC)-1 in C. elegans. We show that CRTC-1 specifically uncouples AMPK/calcineurin-mediated effects on lifespan from pleiotropic side effects by reprogramming mitochondrial and metabolic function. This pro-longevity metabolic state is regulated cell nonautonomously by CRTC-1 in the nervous system. Neuronal CRTC-1/CREB regulates peripheral metabolism antagonistically with the functional PPARα ortholog, NHR-49, drives mitochondrial fragmentation in distal tissues, and suppresses the effects of AMPK on systemic mitochondrial metabolism and longevity via a cell-nonautonomous catecholamine signal. These results demonstrate that while both local and distal mechanisms combine to modulate aging, distal regulation overrides local contribution. Targeting central perception of energetic state is therefore a potential strategy to promote healthy aging.

  19. Connections Matter: Social Networks and Lifespan Health in Primate Translational Models

    Science.gov (United States)

    McCowan, Brenda; Beisner, Brianne; Bliss-Moreau, Eliza; Vandeleest, Jessica; Jin, Jian; Hannibal, Darcy; Hsieh, Fushing

    2016-01-01

    Humans live in societies full of rich and complex relationships that influence health. The ability to improve human health requires a detailed understanding of the complex interplay of biological systems that contribute to disease processes, including the mechanisms underlying the influence of social contexts on these biological systems. A longitudinal computational systems science approach provides methods uniquely suited to elucidate the mechanisms by which social systems influence health and well-being by investigating how they modulate the interplay among biological systems across the lifespan. In the present report, we argue that nonhuman primate social systems are sufficiently complex to serve as model systems allowing for the development and refinement of both analytical and theoretical frameworks linking social life to health. Ultimately, developing systems science frameworks in nonhuman primate models will speed discovery of the mechanisms that subserve the relationship between social life and human health. PMID:27148103

  20. Nutrition through the life-span. Part 1: preconception, pregnancy and infancy.

    Science.gov (United States)

    Shepherd, Alison Anne

    Good nutrition throughout the life-span is fundamental if infants are to grow into healthy adults with subsequent progression through to old age. However, with an alarming increase in both the rates of obesity and malnutrition, it would seem prudent to suggest that infants, children and adults are not achieving an adequate nutritional status. This article is part one of a two-part series which aims to educate nurses by giving some guidelines on how such individuals may achieve a healthy nutritional status right through from preconception, pregnancy, infancy and childhood, through to adulthood and old age. It should always be remembered that although nurses are in a prime position to identify and treat malnutrition, it is not just a nursing responsibility. Safe and effective nutritional care can only be delivered if all those involved in the care of the patient - dieticians, nutritionists, doctors and pharmacists - are working together.

  1. Chlorophyll enhances oxidative stress tolerance in Caenorhabditis elegans and extends its lifespan

    Science.gov (United States)

    Wang, Erjia

    2016-01-01

    Green vegetables are thought to be responsible for several beneficial properties such as antioxidant, anti-mutagenic, and detoxification activities. It is not known whether these effects are due to chlorophyll which exists in large amounts in many foods or result from other secondary metabolites. In this study, we used the model system Caenorhabditis elegans to investigate the anti-oxidative and anti-aging effects of chlorophyll in vivo. We found that chlorophyll significantly improves resistance to oxidative stress. It also enhances the lifespan of C. elegans by up to 25% via activation of the DAF-16/FOXO-dependent pathway. The results indicate that chlorophyll is absorbed by the worms and is thus bioavailable, constituting an important prerequisite for antioxidant and longevity-promoting activities inside the body. Our study thereby supports the view that green vegetables may also be beneficial for humans. PMID:27077003

  2. Diet across the Lifespan and the Association with Breast Density in Adulthood

    Directory of Open Access Journals (Sweden)

    Jessica Lindgren

    2013-01-01

    Full Text Available Studies have shown inconsistent results regarding the association between dietary factors across the lifespan and breast density and breast cancer in women. Breast density is a strong risk factor for breast cancer, and the mechanism through which it influences cancer risk remains unclear. Breast density has been shown to be modifiable, potentially through dietary modifications. The goal of this paper is to summarize the current studies on diet and diet-related factors across all ages, determine which dietary factors show the strongest association with breast density, the most critical age of exposure, and identify future directions. We identified 28 studies, many of which are cross-sectional, and found that the strongest associations are among vitamin D, calcium, dietary fat, and alcohol in premenopausal women. Longitudinal studies with repeated dietary measures as well as the examination of overall diet over time are needed to confirm these findings.

  3. Loss of NDG-4 extends lifespan and stress resistance in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Brejning, Jeanette; Nørgaard, Steffen; Schøler, Lone Vedel

    2014-01-01

    NDG-4 is a predicted transmembrane acyltransferase protein that acts in the distribution of lipophilic factors. Consequently, ndg-4 mutants lay eggs with a pale appearance due to lack of yolk, and they are resistant to sterility caused by dietary supplementation with the long-chain omega-6...... polyunsaturated fatty acid dihommogamma-linolenic acid (DGLA). Two other proteins, NRF-5 and NRF-6, a homolog of a mammalian secreted lipid binding protein and a NDG-4 homolog, respectively, have previously been shown to function in the same lipid transport pathway. Here, we report that mutation of the NDG-4...... hormone receptor NHR-80 (HNF4 homolog) is required for longevity in germline less animals. We find that NHR-80 is also required for longevity of ndg-4 mutants. Moreover, we find that nrf-5 and nrf-6 mutants also have extended lifespan and increased stress resistance, suggesting that altered lipid...

  4. Applying the genetic theories of ageing to the cytoplasm: cytoplasmic genetic covariation for fitness and lifespan.

    Science.gov (United States)

    Dowling, D K; Maklakov, A A; Friberg, U; Hailer, F

    2009-04-01

    Two genetic models exist to explain the evolution of ageing - mutation accumulation (MA) and antagonistic pleiotropy (AP). Under MA, a reduced intensity of selection with age results in accumulation of late-acting deleterious mutations. Under AP, late-acting deleterious mutations accumulate because they confer beneficial effects early in life. Recent studies suggest that the mitochondrial genome is a major player in ageing. It therefore seems plausible that the MA and AP models will be relevant to genomes within the cytoplasm. This possibility has not been considered previously. We explore whether patterns of covariation between fitness and ageing across 25 cytoplasmic lines, sampled from a population of Drosophila melanogaster, are consistent with the genetic associations predicted under MA or AP. We find negative covariation for fitness and the rate of ageing, and positive covariation for fitness and lifespan. Notably, the direction of these associations is opposite to that typically predicted under AP.

  5. REMARKS ON THE LIFESPAN FOR THE SOLUTION TO NONLINEAR WAVE EQUATIONS IN THREE SPACE DIMENSIONS

    Institute of Scientific and Technical Information of China (English)

    杨晗; 刘法贵

    2003-01-01

    The authors consider the Cauchy problem for the following nonlinear waveequationsutt - △u = | vl2,vtt - △v = (△u)2,u(0, x) = εuo(x), ut(0, x) = ε(x),v(0, x) = εvo(x), vt(0, x) = εv1(x),where x ∈ R3, t ≥ 0, ε> 0 is a small parameter, and obtain the sharp bounds for thelifespan of solution to (0.1). Specially, it is proved that there exist two constants C1 andC2, which are independent of ε, then the lifespan T(ε) satisfies the folowing inequalitiesC1 ≤ limε→0ε In T(ε) ≤ C2.

  6. Effects of Synthetic Diets Enriched in Specific Nutrients on Drosophila Development, Body Fat, and Lifespan.

    Directory of Open Access Journals (Sweden)

    Tânia Reis

    Full Text Available Gene-diet interactions play a crucial but poorly understood role in susceptibility to obesity. Accordingly, the development of genetically tractable model systems to study the influence of diets in obesity-prone genetic backgrounds is a focus of current research. Here I present a modified synthetic Drosophila diet optimized for timely larval development, a stage dedicated to energy storage. Specifically increasing the levels of individual macronutrients-carbohydrate, lipid, or protein-resulted in markedly different organismal effects. A high-carbohydrate diet adversely affected the timing of development, size, early lifespan and body fat. Strikingly, quadrupling the amount of dietary lipids had none of these effects. Diets rich in protein appeared to be the most beneficial, as larvae developed faster, with no change in size, into long-lived adults. I believe this synthetic diet will significantly facilitate the study of gene-diet interactions in organismal energy balance.

  7. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents.

    Science.gov (United States)

    Ryu, Dongryeol; Mouchiroud, Laurent; Andreux, Pénélope A; Katsyuba, Elena; Moullan, Norman; Nicolet-Dit-Félix, Amandine A; Williams, Evan G; Jha, Pooja; Lo Sasso, Giuseppe; Huzard, Damien; Aebischer, Patrick; Sandi, Carmen; Rinsch, Chris; Auwerx, Johan

    2016-08-01

    The biological effects of urolithins remain poorly characterized, despite wide-spread human exposure via the dietary consumption of their metabolic precursors, the ellagitannins, which are found in the pomegranate fruit, as well as in nuts and berries. We identified urolithin A (UA) as a first-in-class natural compound that induces mitophagy both in vitro and in vivo following oral consumption. In C. elegans, UA prevented the accumulation of dysfunctional mitochondria with age and extended lifespan. Likewise, UA prolonged normal activity during aging in C. elegans, including mobility and pharyngeal pumping, while maintaining mitochondrial respiratory capacity. These effects translated to rodents, where UA improved exercise capacity in two different mouse models of age-related decline of muscle function, as well as in young rats. Our findings highlight the health benefits of urolithin A and its potential application in strategies to improve mitochondrial and muscle function.

  8. Brain in macro experiential context: biocultural co-construction of lifespan neurocognitive development.

    Science.gov (United States)

    Li, Shu-Chen

    2009-01-01

    For more than a century, neuroscientists have recognized that the brain is an open, adaptive system and that the organism's experiences are environmentally contextualized. However, the proposition that socio-cultural contexts may exert reciprocal influences on neurobiological mechanisms is rarely considered and could not be empirically explored until very recently. This article reviews the emerging trend of interdisciplinary research aiming at exploring the effects of socio-cultural influences on human brain functioning. Recent co-constructive views of brain development and functioning and empirical evidence of developmental plasticity at different levels are reviewed. Empirical findings that are indicative of reciprocal influences of social contexts, culture-specific language environment, and expertise training are highlighted. The quest to understand how individual brains get personalized through lifespan development that takes place in the macro socio-cultural experiential context is still at an embryonic stage. Nevertheless, studies reviewed here indicate that new conceptual and empirical opportunities for this endeavor are emerging.

  9. Effects of Synthetic Diets Enriched in Specific Nutrients on Drosophila Development, Body Fat, and Lifespan.

    Science.gov (United States)

    Reis, Tânia

    2016-01-01

    Gene-diet interactions play a crucial but poorly understood role in susceptibility to obesity. Accordingly, the development of genetically tractable model systems to study the influence of diets in obesity-prone genetic backgrounds is a focus of current research. Here I present a modified synthetic Drosophila diet optimized for timely larval development, a stage dedicated to energy storage. Specifically increasing the levels of individual macronutrients-carbohydrate, lipid, or protein-resulted in markedly different organismal effects. A high-carbohydrate diet adversely affected the timing of development, size, early lifespan and body fat. Strikingly, quadrupling the amount of dietary lipids had none of these effects. Diets rich in protein appeared to be the most beneficial, as larvae developed faster, with no change in size, into long-lived adults. I believe this synthetic diet will significantly facilitate the study of gene-diet interactions in organismal energy balance.

  10. Self-Reported Ageism Across the Lifespan: Role of Aging Knowledge.

    Science.gov (United States)

    Cherry, Katie E; Brigman, Susan; Lyon, Bethany A; Blanchard, Blakeley; Walker, Erin J; Smitherman, Emily A

    2016-10-01

    The authors examined the prevalence of self-reported ageist behaviors in a lifespan sample ranging in age from 13 to 91 years. Participants completed the Relating to Older People Evaluation (Cherry & Palmore). Results indicated that adolescents and young adults reported fewer ageist behaviors overall than did middle-aged and older adults. Positive ageist behaviors were more frequent than negative ageist behaviors for people of all ages. Women endorsed positive ageism items more often than men, although men and women did not differ in frequency of negative ageist behaviors. Follow-up analyses on participants' responses to two knowledge of aging measures, the Facts on Aging Quiz and the Knowledge of Memory Aging Questionnaire, showed that knowledge of aging was significantly correlated with negative ageist behaviors, after controlling for age and gender. Implications of these findings for current views of ageism (positive and negative) are discussed.

  11. Arm-Gal4 inheritance influences development and lifespan in Drosophila melanogaster.

    Science.gov (United States)

    Slade, F A; Staveley, B E

    2015-10-19

    The UAS-Gal4 ectopic expression system is a widely used and highly valued tool that allows specific gene expression in Drosophila melanogaster. Yeast transcription factor Gal4 can be directed using D. melanogaster transcriptional control elements, and is often assumed to have little effect on the organism. By evaluation of the consequences of maternal and paternal inheritance of a Gal4 transgene under the transcriptional regulation of armadillo control elements (arm-Gal4), we demonstrated that Gal4 expression could be detrimental to development and longevity. Male progeny expressing arm-Gal4 in the presence of UAS-lacZ transgene had reduced numbers and size of ommatidia, compared to flies expressing UAS-lacZ transgene under the control of other Gal4 transgenes. Aged at 25°C, the median life span of male flies with maternally inherited elav-Gal4 was 70 days, without a responding transgene or with UAS-lacZ. The median life span of maternally inherited arm-Gal4 male flies without a responding transgene was 48 days, and 40 days with the UAS-lacZ transgene. A partial rescue of this phenotype was observed with the expression of UAS-lacZ under paternal arm-Gal4 control, having an average median lifespan of 60 days. This data suggests that arm-Gal4 has detrimental effects on Drosophila development and lifespan that are directly dependent upon parental inheritance, and that the benign responder and reporter gene UAS-lacZ may influence D. melanogaster development. These findings should be taken into consideration during the design and execution of UAS-Gal4 expression experiments.

  12. Equations to describe brain size across the continuum of human lifespan.

    Science.gov (United States)

    Borzage, Matthew; Blüml, Stefan; Seri, Istvan

    2014-01-01

    Equations fitting the normative values for gender-specific brain size changes are available. However, these equations do not fit for all age ranges across the human lifespan and particularly have failed to examine the fit across the continuum of prenatal and postnatal human life. We sought to develop a parametric equation that best describes the changes in gender-specific brain size as a function of age across the continuum of prenatal and postnatal human life. Brain weight and brain volume data retrieved from the literature were combined to perform a meta-analysis. Additions to previously published findings included collecting a dataset that spanned the continuum of human lifespan, logarithmic transformation of the data and utilization of the Birch equation. We used Akaike's Information Criterion (AIC) for quantitative evaluation of the new equations. A total of 2,011 brain weight data points spanning from 10 weeks of fetal gestation to over 90 years of age were retrieved. Using our approach, we developed equations with improved fits and lower or similar AIC values compared to the published equations. The new equations are modifications of the basic Birch model. These equations are the first to describe the gender-specific brain weight changes through the continuum of both prenatal and postnatal human life while achieving a level of accuracy similar to or better than the previous, more age-restricted models. The new equations are improved compared to previously used equations and may be useful to those who study brain development, particularly researchers interested in prenatal and postnatal brain size.

  13. Loss of glial lazarillo, a homolog of apolipoprotein D, reduces lifespan and stress resistance in Drosophila.

    Science.gov (United States)

    Sanchez, Diego; López-Arias, Begoña; Torroja, Laura; Canal, Inmaculada; Wang, Xiaohui; Bastiani, Michael J; Ganfornina, Maria D

    2006-04-01

    The vertebrate Apolipoprotein D (ApoD) is a lipocalin secreted from subsets of neurons and glia during neural development and aging . A strong correlation exists between ApoD overexpression and numerous nervous system pathologies as well as obesity, diabetes, and many forms of cancer . However, the exact relationship between the function of ApoD and the pathophysiology of these diseases is still unknown. We have generated loss-of-function Drosophila mutants for the Glial Lazarillo (GLaz) gene , a homolog of ApoD in the fruit fly, mainly expressed in subsets of adult glial cells. The absence of GLaz reduces the organism's resistance to oxidative stress and starvation and shortens male lifespan. The mutant flies exhibit a smaller body mass due to a lower amount of neutral lipids stored in the fat body. Apoptotic neural cell death increases in aged flies or upon paraquat treatment, which also impairs neural function as assessed by behavioral tests. The higher sensitivity to oxidative stress and starvation and the reduced fat storage revert to control levels when a GFP-GLaz fusion protein is expressed under the control of the GLaz natural promoter. Finally, GLaz mutants have a higher concentration of lipid peroxidation products, pointing to a lipid peroxidation protection or scavenging as the mechanism of action for this lipocalin. In agreement with Walker et al. (, in this issue of Current Biology), who analyze the effects of overexpressing GLaz, we conclude that GLaz has a protective role in stress situations and that its absence reduces lifespan and accelerates neurodegeneration.

  14. Older people with incurable cancer: Existential meaning-making from a life-span perspective.

    Science.gov (United States)

    Haug, Sigrid Helene Kjørven; Danbolt, Lars J; Kvigne, Kari; DeMarinis, Valerie

    2016-02-01

    An increasing number of older people in Western countries are living with incurable cancer, receiving palliative care from specialized healthcare contexts. The aim of our article was to understand how they experience the existential meaning-making function in daily living from a life-span perspective. Some 21 participants (12 men and 9 women), aged 70-88, were interviewed in a semistructured framework. They were recruited from somatic hospitals in southeastern Norway. We applied the model of selective optimization with compensation (SOC) from life-span developmental psychology in a deductive manner to explore the participants' life-oriented adaptive strategies. A meaning component was added to the SOC model. The participants experienced the existential meaning-making function on two levels. On a superordinate level, it was an important component for interpreting and coordinating the adaptive strategies of SOC for reaching the most important goals in daily living. The existential meaning-making framework provided for a comprehensive understanding of resilience, allowing for both restoration and growth components to be identified. The second level was related to strategy, in that the existential meaning-making function was involved in a complex interaction with behavioral resources and resilience, leading to continuation of goals and more realistic goal adjustments. A few experienced existential meaning-making dysfunction. The modified SOC model was seen as applicable for palliative care in specialized healthcare contexts. Employing the existential meaning-making framework with its complementary understanding of resilience as growth potential to the SOC model's restoration potential can help older people to identify how they make meaning and how this influences their adaptation process to being incurably sick.

  15. The developmental trajectory of hippocampus across the human lifespan based on multimodal neuroimaging

    Directory of Open Access Journals (Sweden)

    Xiu WANG

    2014-04-01

    Full Text Available Background During the last 2 decades, more and more functional MRI (fMRI researches have increasingly focused on both structures and functions of the hippocampal region to discover the relationship between hippocampus and memory. In order to reveal the normative pattern of individual development or aging processes of the hippocampus or further memory-related disease prediction, an investigation on such a brain structure's trajectory across the human lifespan is necessary.  Methods Regional volume is the most commonly used variable for the structural change of normal brain. The regional homogeneity (ReHo and amplitude of low-frequency fluctuation (ALFF are the two test-retest reliable metrics for detection of functional changes. We here investigate ReHo, ALFF and fractional ALFF (fALFF based upon both structural and resting state fMRI of 125 subjects from 7 to 85 years old.  Results As results, significant age-related decreases were detected for volumes of bilateral hippocampus (corrected Ps = 0.000. In contrast, ALFF (corrected P = 0.034, β = -0.314, fALFF (corrected P = 0.059, β = - 0.687 and ReHo (corrected P = 0.005, β = - 0.330 demonstrated a trend of negative linear correlation with age in the left hippocampus.  Conclusions Our findings partly reflect the structure-function relationship of the hippocampus during the human lifespan. doi: 10.3969/j.issn.1672-6731.2014.04.006

  16. New Genes Tied to Endocrine, Metabolic, and Dietary Regulation of Lifespan from a Caenorhabditis elegans Genomic RNAi Screen.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available Most of our knowledge about the regulation of aging comes from mutants originally isolated for other phenotypes. To ask whether our current view of aging has been affected by selection bias, and to deepen our understanding of known longevity pathways, we screened a genomic Caenorhabditis elegans RNAi library for clones that extend lifespan. We identified 23 new longevity genes affecting signal transduction, the stress response, gene expression, and metabolism and assigned these genes to specific longevity pathways. Our most important findings are (i that dietary restriction extends C. elegans' lifespan by down-regulating expression of key genes, including a gene required for methylation of many macromolecules, (ii that integrin signaling is likely to play a general, evolutionarily conserved role in lifespan regulation, and (iii that specific lipophilic hormones may influence lifespan in a DAF-16/FOXO-dependent fashion. Surprisingly, of the new genes that have conserved sequence domains, only one could not be associated with a known longevity pathway. Thus, our current view of the genetics of aging has probably not been distorted substantially by selection bias.

  17. Extended lifespan, reduced body size and leg skeletal muscle mass, and decreased mitochondrial function in clk-1 transgenic mice.

    Science.gov (United States)

    Takahashi, Kazuhide; Noda, Yoshihiro; Ohsawa, Ikuroh; Shirasawa, Takuji; Takahashi, Mayumi

    2014-10-01

    Mutational inactivation of clk-1, which encodes an enzyme necessary for the biosynthesis of coenzyme Q (CoQ), extends the lifespan of Caenorhabditis elegans. However, whether mammalian clk-1 regulates the lifespan of mice is not known because clk-1-deficiencies are embryonic lethal. Here, we investigated the lifespan of clk-1 transgenic mice (Tg96/I), which were rescued from embryonic lethality via the transgenic expression of mouse clk-1. Tg96/I mice lived longer and had smaller bodies than wild-type mice, but Tg96/I mice had CoQ levels equivalent to wild-type mice. The small-sized Tg96/I mice exhibited reduced whole-body oxygen consumption (VO2) during the dark period, and lean leg skeletal muscles with reduced mitochondrial VO2 and ATP content compared with wild-type mice. These findings indicate a close relationship between lifespan extension and decreased mitochondrial function, which was induced by the transgenic expression of clk-1, in leg skeletal muscles that exhibit high metabolic activity.

  18. A cross-cultural study of the lifespan distributions of life script events and autobiographical memories of life story events

    DEFF Research Database (Denmark)

    Zaragoza Scherman, Alejandra; Salgado, Sinué; Shao, Zhifang

    of major transitional life events in an idealized life course. By comparing the lifespan distribution of life scripts events and memories of life story events, we can determine the degree to which the cultural life script serves as a recall template for autobiographical memories, especially of positive...

  19. Tissue-level leaf toughness, but not lamina thickness, predicts sapling leaf lifespan and shade tolerance of tropical tree species

    NARCIS (Netherlands)

    Kitajima, K.; Poorter, L.

    2010-01-01

    Leaf toughness is thought to enhance physical defense and leaf lifespan. Here, we evaluated the relative importance of tissue-level leaf traits vs lamina thickness, as well as their ontogenetic changes, for structure-level leaf toughness and regeneration ecology of 19 tropical tree species. We

  20. Lifespan and Reproductive Senescence in a Free-Ranging Ring-Tailed Lemur (Lemur catta) Population at Berenty, Madagascar.

    Science.gov (United States)

    Ichino, Shinichiro; Soma, Takayo; Miyamoto, Naomi; Chatani, Kaoru; Sato, Hiroki; Koyama, Naoki; Takahata, Yukio

    2015-01-01

    The lifespan and age-specific fecundity of female ring-tailed lemurs (Lemur catta) were estimated from a 24-year longitudinal dataset based on individual identification at Berenty Reserve, Madagascar. The mean lifespan of females in 10-year (1989-1998) birth cohorts was 4.9 ± 4.9 years (n = 77), and the longest recorded lifespan in the population was 20 years. The mortality rate of adult females increased to ≥20% at 10-11 years old and reached 33-50% at 12-15 years old. Although the birth rate of old females (12-17 years old) was 72.0%, slightly lower than that of prime adult females (4-11 years old), i.e. 80.2%, no significant difference was found between them. Half of the females who reached the age of 12 years gave birth in the last year of their life. The oldest mother to give birth was 17 years old. These results suggest that most females can maintain reproductive performance in their later life and that there is no evidence for a postreproductive lifespan in this species. © 2015 S. Karger AG, Basel.

  1. Resistance to oxidative stress induced by paraquat correlates well with both decreased and increased lifespan in Drosophila melanogaster

    NARCIS (Netherlands)

    Vermeulen, CJ; Van De Zande, L; Bijlsma, R

    2005-01-01

    There is increasing support for the notion that genetic variation for lifespan, both within and between species, is correlated with variation in the efficiency of the free radical scavenging system and the ability to withstand oxidative stress. In Drosophila, resistance to dietary paraquat, a free r

  2. Assessment of Lifespan Functioning Attainment (ALFA) scale: A quantitative interview for self-reported current and functional decline in schizophrenia.

    Science.gov (United States)

    Joseph, Jamie; Kremen, William S; Glatt, Stephen J; Franz, Carol E; Chandler, Sharon D; Liu, Xiaohua; Johnson, Barbara K; Tsuang, Ming T; Twamley, Elizabeth W

    2015-06-01

    Schizophrenia has been characterized as a disorder with poor outcomes across various functional domains, especially social and occupational functioning. Although these outcomes have been investigated based on patients' current functioning, few studies have considered the assessment of functional outcomes across the lifespan in schizophrenia. We developed a novel and brief scale of adulthood lifespan functioning, the Assessment of Lifespan Functioning Attainment (ALFA). We assessed current functioning and percentage of pre- and post-psychosis onset engagement for five functional domains including paid employment, living independently, romantic partnerships, close friendships, and recreational engagement with others. Pre-to post-psychosis functional decline was observed for all domains, with paid employment having the greatest decline (d = 2.68) and living independently having the least decline (d = .59). Our exploratory factor analysis suggests that a single factor accounted for the most variance in Pre-Psychosis Functioning in ALFA domains. Two factors explain the majority of variance in Post-Psychosis Functioning and Pre-to-Post Psychosis Decline: a sociability factor (close friendships and recreational engagement with others) and an independence factor (paid employment, living independently, romantic relationships). To our knowledge, this is the first study to report on a self-reported quantitative assessment of adult lifespan functioning in schizophrenia. The ALFA scale may be a useful tool for future research on functional outcomes in schizophrenia.

  3. A Steroidal Saponin from Ophiopogon japonicus Extends the Lifespan of Yeast via the Pathway Involved in SOD and UTH1

    Science.gov (United States)

    Sun, Kaiyue; Cao, Shining; Pei, Liang; Matsuura, Akira; Xiang, Lan; Qi, Jianhua

    2013-01-01

    Nolinospiroside F is a steroidal saponin isolated from Ophiopogon japonicus (O. japonicus). In this study, we found that nolinospiroside F significantly extends the replicative lifespan of K6001 yeast at doses of 1, 3 and 10 μM, indicating that it has an anti-aging effect. This may be attributed to its anti-oxidative effect, as nolinospiroside F could increase yeast survival under oxidative stress conditions and decrease the level of malondialdehyde (MDA), an oxidative stress biomarker. It could also increase anti-oxidative stress genes, SOD1 and SOD2, expression, and the activity of superoxide dismutase (SOD). It increase the activity of SIRT1, an upstream inducer of SOD2 expression. In sod1 and sod2 mutant yeast strains, nolinospiroside F failed to extend their replicative lifespan. These results indicate that SOD participates in the anti-aging effect of nolinospiroside F. Furthermore, nolinospiroside F inhibited the expression of UTH1, a yeast-aging gene that is involved in the oxidative stress of yeast, and failed to extend the replicative lifespan of uth1 or skn7 mutant yeast cells. SKN7 is the transcriptional activator of UTH1. We also demonstrate that SOD and UTH1 regulate each other’s expression. Together, these results suggest that SOD and UTH1 genes are required for and play interactive roles in nolinospiroside F-mediated yeast lifespan extension. PMID:23439553

  4. The cost of mating: influences of life history traits and mating strategies on lifespan in two closely related Yponomeuta species

    NARCIS (Netherlands)

    Bakker, A.C.; Campos Louçã, J.; Roessingh, P.; Menken, S.B.J.

    2011-01-01

    Theory predicts that in monandrous butterfly species males should not invest in a long lifespan because receptive females quickly disappear from the mating population. In polyandrous species, however, it pays for males to invest in longevity, which increases the number of mating opportunities and

  5. Diacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating TOR signaling in Drosophila and C. elegans.

    Science.gov (United States)

    Lin, Yen-Hung; Chen, Yi-Chun; Kao, Tzu-Yu; Lin, Yi-Chun; Hsu, Tzu-En; Wu, Yi-Chun; Ja, William W; Brummel, Theodore J; Kapahi, Pankaj; Yuh, Chiou-Hwa; Yu, Lin-Kwei; Lin, Zhi-Han; You, Ru-Jing; Jhong, Yi-Ting; Wang, Horng-Dar

    2014-08-01

    Target of rapamycin (TOR) signaling is a nutrient-sensing pathway controlling metabolism and lifespan. Although TOR signaling can be activated by a metabolite of diacylglycerol (DAG), phosphatidic acid (PA), the precise genetic mechanism through which DAG metabolism influences lifespan remains unknown. DAG is metabolized to either PA via the action of DAG kinase or 2-arachidonoyl-sn-glycerol by diacylglycerol lipase (DAGL). Here, we report that in Drosophila and Caenorhabditis elegans, overexpression of diacylglycerol lipase (DAGL/inaE/dagl-1) or knockdown of diacylglycerol kinase (DGK/rdgA/dgk-5) extends lifespan and enhances response to oxidative stress. Phosphorylated S6 kinase (p-S6K) levels are reduced following these manipulations, implying the involvement of TOR signaling. Conversely, DAGL/inaE/dagl-1 mutants exhibit shortened lifespan, reduced tolerance to oxidative stress, and elevated levels of p-S6K. Additional results from genetic interaction studies are consistent with the hypothesis that DAG metabolism interacts with TOR and S6K signaling to affect longevity and oxidative stress resistance. These findings highlight conserved metabolic and genetic pathways that regulate aging.

  6. Target of rapamycin signalling mediates the lifespan-extending effects of dietary restriction by essential amino acid alteration

    NARCIS (Netherlands)

    Emran, S.; Yang, M.Y.; He, X.L.; Zandveld, J.; Piper, M.D.W.

    2014-01-01

    Dietary restriction (DR), defined as a moderate reduction in food intake short of malnutrition, has been shown to extend healthy lifespan in a diverse range of organisms, from yeast to primates. Reduced signalling through the insulin/IGF-like (IIS) and Target of Rapamycin (TOR) signalling pathways a

  7. Resistance to oxidative stress induced by paraquat correlates well with both decreased and increased lifespan in Drosophila melanogaster

    NARCIS (Netherlands)

    Vermeulen, CJ; Van De Zande, L; Bijlsma, R

    2005-01-01

    There is increasing support for the notion that genetic variation for lifespan, both within and between species, is correlated with variation in the efficiency of the free radical scavenging system and the ability to withstand oxidative stress. In Drosophila, resistance to dietary paraquat, a free

  8. How changes in subjective general health predict future time perspective, and development and generativity motives over the lifespan

    NARCIS (Netherlands)

    Kooij, D.T.A.M.; Voorde, F.C. van de

    2011-01-01

    In this study, we used the lifespan theories of selection optimization and compensation (SOC) and the socio-emotional selectivity theory (SST) to integrate the disengagement and activity perspectives on aging and to explain intra-individual changes in work motivation. A two-wave longitudinal survey

  9. Exploring the Processes of Self-Development Encountered by Adult Returners to Higher Education: A Lifespan Psychology Perspective

    Science.gov (United States)

    Mercer, Jenny

    2010-01-01

    Evidence indicates that non-traditional adult returners describe returning to education as a period of self-development and growth. However, lifespan psychology perspectives also show that successful growth and change involves periods of conflict. This paper will explore both the nature of self-development and conflicts experienced by a sample of…

  10. Event-based prospective memory across the lifespan: Do all age groups benefit from salient prospective memory cues?

    NARCIS (Netherlands)

    Kretschmer-Trendowicz, A.; Altgassen, A.M.

    2016-01-01

    The present study investigated effects of cognitive control demands on prospective memory (PM) performance across the lifespan. Four different age groups (children, adolescents, young adults, old adults) worked on a computer-based picture categorization task as ongoing activity, while PM cue salienc

  11. Repeated intra-specific divergence in lifespan and ageing of African annual fishes along an aridity gradient

    DEFF Research Database (Denmark)

    Blažek, Radim; Polačik, Matej; Kačer, Petr

    2016-01-01

    to extended lifespan and slower ageing as a consequence of condition-dependent survival. Using within-species contrasts of eight natural populations of Nothobranchius fishes in common garden experiments, we demonstrate that populations originating from dry regions (with short life expectancy) had shorter...

  12. The Lifespan Self-Esteem Scale: Initial Validation of a New Measure of Global Self-Esteem.

    Science.gov (United States)

    Harris, Michelle A; Donnellan, M Brent; Trzesniewski, Kali H

    2017-02-21

    This article introduces the Lifespan Self-Esteem Scale (LSE), a short measure of global self-esteem suitable for populations drawn from across the lifespan. Many existing measures of global self-esteem cannot be used across multiple developmental periods due to changes in item content, response formats, and other scale characteristics. This creates a need for a new lifespan scale so that changes in global self-esteem over time can be studied without confounding maturational changes with alterations in the measure. The LSE is a 4-item measure with a 5-point response format using items inspired by established self-esteem scales. The scale is essentially unidimensional and internally consistent, and it converges with existing self-esteem measures across ages 5 to 93 (N = 2,714). Thus, the LSE appears to be a useful measure of global self-esteem suitable for use across the lifespan as well as contexts where a short measure is desirable, such as populations with short attention spans or large projects assessing multiple constructs. Moreover, the LSE is one of the first global self-esteem scales to be validated for children younger than age 8, which provides the opportunity to broaden the field to include research on early formation and development of global self-esteem, an area that has previously been limited.

  13. Macromitophagy is a longevity assurance process that in chronologically aging yeast limited in calorie supply sustains functional mitochondria and maintains cellular lipid homeostasis

    Science.gov (United States)

    Burstein, Michelle T.; Koupaki, Olivia; Gomez-Perez, Alejandra; Levy, Sean; Pluska, Lukas; Mattie, Sevan; Rafeh, Rami; Iouk, Tatiana; Sheibani, Sara; Greenwood, Michael; Vali, Hojatollah; Titorenko, Vladimir I.

    2013-01-01

    Macromitophagy controls mitochondrial quality and quantity. It involves the sequestration of dysfunctional or excessive mitochondria within double-membrane autophagosomes, which then fuse with the vacuole/lysosome to deliver these mitochondria for degradation. To investigate a physiological role of macromitophagy in yeast, we examined how the atg32Δ-dependent mutational block of this process influences the chronological lifespan of cells grown in a nutrient-rich medium containing low (0.2%) concentration of glucose. Under these longevity-extending conditions of caloric restriction (CR) yeast cells are not starving. We also assessed a role of macromitophagy in lifespan extension by lithocholic acid (LCA), a bile acid that prolongs yeast longevity under CR conditions. Our findings imply that macromitophagy is a longevity assurance process underlying the synergistic beneficial effects of CR and LCA on yeast lifespan. Our analysis of how the atg32Δ mutation influences mitochondrial morphology, composition and function revealed that macromitophagy is required to maintain a network of healthy mitochondria. Our comparative analysis of the membrane lipidomes of organelles purified from wild-type and atg32Δ cells revealed that macromitophagy is required for maintaining cellular lipid homeostasis. We concluded that macromitophagy defines yeast longevity by modulating vital cellular processes inside and outside of mitochondria. PMID:23553280

  14. Task Group 7B: Cellular and Molecular Mechanisms of Biological Aging: The Roles of Nature, Nurture and Chance in the Maintenance of Human Healthspan

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz-Ulrich; Arya, Suresh; Grant, Christine; Miller, Linda; Ono, Santa Jeremy; Patil, Chris; Shay, Jerry; Topol, Eric; Torry, Michael; Weier, Heinz-Ulrich G.; Tse, Iris; Lin, Su-Ju; Miller, Richard

    2007-11-14

    The degree to which an individual organism maintains healthspan and lifespan is a function of complex interactions between genetic inheritance ('nature'), environment, including cultural inheritance (nurture) and stochastic events ('luck' or 'chance'). This task group will focus upon the role of chance because it is so poorly understood and because it appears to be of major importance in the determination of individual variations in healthspan and lifespan within species. The major factor determining variations in healthspan and lifespan between species is genetic inheritance. Broader aspects of cellular and molecular mechanisms of biological aging will also be considered, given their importance for understanding the cellular and molecular basis of successful aging. The task force will consider the cellular and molecular basis for nature, nurture and chance in healthspan and life span determination. On the basis of comparisons between identical and non-identical twins, geneticists have estimated that genes control no more than about a quarter of the inter-individual differences in lifespan (Herskind 1996). Twin studies of very old individuals, however, show substantially greater genetic contributions to Healthspan (McClearn 2004; Reed 2003). The environment clearly plays an important role in the length and the quality of life. Tobacco smoke, for example has the potential to impact upon multiple body systems in ways that appear to accelerate the rates at which those systems age (Bernhard 2007). To document the role of chance events on aging, one must rigorously control both the genetic composition of an organism and its environment. This has been done to a remarkable degree in a species of nematodes, Caenorhabditis elegans (Vanfleteren 1998). The results confirm hundreds of previous studies with a wide range of species, especially those with inbred rodents housed under apparently identical but less well controlled environments. One

  15. Task Group 7B: Cellular and Molecular Mechanisms of Biological Aging: The Roles of Nature, Nurture and Chance in the Maintenance of Human Healthspan

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz-Ulrich; Arya, Suresh; Grant, Christine; Miller, Linda; Ono, Santa Jeremy; Patil, Chris; Shay, Jerry; Topol, Eric; Torry, Michael; Weier, Heinz-Ulrich G.; Tse, Iris; Lin, Su-Ju; Miller, Richard

    2007-11-14

    The degree to which an individual organism maintains healthspan and lifespan is a function of complex interactions between genetic inheritance ('nature'), environment, including cultural inheritance (nurture) and stochastic events ('luck' or 'chance'). This task group will focus upon the role of chance because it is so poorly understood and because it appears to be of major importance in the determination of individual variations in healthspan and lifespan within species. The major factor determining variations in healthspan and lifespan between species is genetic inheritance. Broader aspects of cellular and molecular mechanisms of biological aging will also be considered, given their importance for understanding the cellular and molecular basis of successful aging. The task force will consider the cellular and molecular basis for nature, nurture and chance in healthspan and life span determination. On the basis of comparisons between identical and non-identical twins, geneticists have estimated that genes control no more than about a quarter of the inter-individual differences in lifespan (Herskind 1996). Twin studies of very old individuals, however, show substantially greater genetic contributions to Healthspan (McClearn 2004; Reed 2003). The environment clearly plays an important role in the length and the quality of life. Tobacco smoke, for example has the potential to impact upon multiple body systems in ways that appear to accelerate the rates at which those systems age (Bernhard 2007). To document the role of chance events on aging, one must rigorously control both the genetic composition of an organism and its environment. This has been done to a remarkable degree in a species of nematodes, Caenorhabditis elegans (Vanfleteren 1998). The results confirm hundreds of previous studies with a wide range of species, especially those with inbred rodents housed under apparently identical but less well controlled environments. One

  16. Cellular systems biology profiling applied to cellular models of disease.

    Science.gov (United States)

    Giuliano, Kenneth A; Premkumar, Daniel R; Strock, Christopher J; Johnston, Patricia; Taylor, Lansing

    2009-11-01

    Building cellular models of disease based on the approach of Cellular Systems Biology (CSB) has the potential to improve the process of creating drugs as part of the continuum from early drug discovery through drug development and clinical trials and diagnostics. This paper focuses on the application of CSB to early drug discovery. We discuss the integration of protein-protein interaction biosensors with other multiplexed, functional biomarkers as an example in using CSB to optimize the identification of quality lead series compounds.

  17. Cordyceps sinensis oral liquid prolongs the lifespan of the fruit fly, Drosophila melanogaster, by inhibiting oxidative stress.

    Science.gov (United States)

    Zou, Yingxin; Liu, Yuxiang; Ruan, Minghua; Feng, Xu; Wang, Jiachun; Chu, Zhiyong; Zhang, Zesheng

    2015-10-01

    This study investigated the effect of Cordyceps sinensis oral liquid (CSOL) on the lifespan of Drosophila melanogaster (fruit fly). Following the lifelong treatment of fruit flies with CSOL, lifespan was examined. The activity of copper-zinc-containing superoxide dismutase 1 (SOD1), manganese-containing superoxide dismutase 2 (SOD2) and catalase (CAT), as well as the lipofuscin (LF) content were determined. The mRNA levels of SOD1, SOD2 and CAT were quantified by qPCR. Hydrogen peroxide (H2O2) and paraquat were used to mimic the effects of damage caused by acute oxidative stress. D-galactose was used to mimic chronic pathological aging. CSOL significantly prolonged the lifespan of the fruit flies under physiological conditions. The activity of SOD1 and CAT was upregulated, and LF accumulation was inhibited by CSOL. CSOL had no effect on the transcriptional levels (mRNA) of these enzymes. The survival time of the fruit flies which were negatively affected by exposure to H2O2 or paraquat was significantly prolonged by CSOL. In fruit flies pathologically aged by epxosure to D-galactose, CSOL also significantly prolonged their lifespan, upregulated the activity of SOD1 and CAT, and inhibited LF accumulation. The findings of our study indicate that CSOL prolongs the lifespan of fruit flies through an anti-oxidative stress pathway involving the upregulation of SOD1 and CAT activity and the inhibition of LF accumulation. CSOL may thus be explored as a novel agent for slowing the human aging process.

  18. The interplay between protein L-isoaspartyl methyltransferase activity and insulin-like signaling to extend lifespan in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Shilpi Khare

    Full Text Available The protein L-isoaspartyl-O-methyltransferase functions to initiate the repair of isomerized aspartyl and asparaginyl residues that spontaneously accumulate with age in a variety of organisms. Caenorhabditis elegans nematodes lacking the pcm-1 gene encoding this enzyme display a normal lifespan and phenotype under standard laboratory growth conditions. However, significant defects in development, egg laying, dauer survival, and autophagy have been observed in pcm-1 mutant nematodes when deprived of food and when exposed to oxidative stress. Interestingly, overexpression of this repair enzyme in both Drosophila and C. elegans extends adult lifespan under thermal stress. In this work, we show the involvement of the insulin/insulin-like growth factor-1 signaling (IIS pathway in PCM-1-dependent lifespan extension in C. elegans. We demonstrate that reducing the levels of the DAF-16 downstream transcriptional effector of the IIS pathway by RNA interference reduces the lifespan extension resulting from PCM-1 overexpression. Using quantitative real-time PCR analysis, we show the up-regulation of DAF-16-dependent stress response genes in the PCM-1 overexpressor animals compared to wild-type and pcm-1 mutant nematodes under mild thermal stress conditions. Additionally, similar to other long-lived C. elegans mutants in the IIS pathway, including daf-2 and age-1 mutants, PCM-1 overexpressor adult animals display increased resistance to severe thermal stress, whereas pcm-1 mutant animals survive less long under these conditions. Although we observe a higher accumulation of damaged proteins in pcm-1 mutant nematodes, the basal level of isoaspartyl residues detected in wild-type animals was not reduced by PCM-1 overexpression. Our results support a signaling role for the protein L-isoaspartyl methyltransferase in lifespan extension that involves the IIS pathway, but that may be independent of its function in overall protein repair.

  19. A mild impairment of mitochondrial electron transport has sex-specific effects on lifespan and aging in mice.

    Directory of Open Access Journals (Sweden)

    Bryan G Hughes

    Full Text Available Impairments of various aspects of mitochondrial function have been associated with increased lifespan in various model organisms ranging from Caenorhabditis elegans to mice. For example, disruption of the function of the 'Rieske' iron-sulfur protein (RISP of complex III of the mitochondrial electron transport chain can result in increased lifespan in the nematode worm C. elegans. However, the mechanisms by which impaired mitochondrial function affects aging remain under investigation, including whether or not they require decreased electron transport. We have generated knock-in mice with a loss-of-function Risp mutation that is homozygous lethal. However, heterozygotes (Risp(+/P224S were viable and had decreased levels of RISP protein and complex III enzymatic activity. This decrease was sufficient to impair mitochondrial respiration and to decrease overall metabolic rate in males, but not females. These defects did not appear to exert an overtly deleterious effect on the health of the mutants, since young Risp(+/P224S mice are outwardly normal, with unaffected performance and fertility. Furthermore, biomarkers of oxidative stress were unaffected in both young and aged animals. Despite this, the average lifespan of male Risp(+/P224S mice was shortened and aged Risp(+/P224S males showed signs of more rapidly deteriorating health. In spite of these differences, analysis of Gompertz mortality parameters showed that Risp heterozygosity decreased the rate of increase of mortality with age and increased the intrinsic vulnerability to death in both sexes. However, the intrinsic vulnerability was increased more dramatically in males, which resulted in their shortened lifespan. For females, the slower acceleration of age-dependent mortality results in significantly increased survival of Risp(+/P224S mice in the second half of lifespan. These results demonstrate that even relatively small perturbations of the mitochondrial electron transport chain can

  20. Estimation of lifespan and economy parameters of steam-turbine power units in thermal power plants using varying regimes

    Science.gov (United States)

    Aminov, R. Z.; Shkret, A. F.; Garievskii, M. V.

    2016-08-01

    The use of potent power units in thermal and nuclear power plants in order to regulate the loads results in intense wear of power generating equipment and reduction in cost efficiency of their operation. We review the methodology of a quantitative assessment of the lifespan and wear of steam-turbine power units and estimate the effect of various operation regimes upon their efficiency. To assess the power units' equipment wear, we suggest using the concept of a turbine's equivalent lifespan. We give calculation formulae and an example of calculation of the lifespan of a steam-turbine power unit for supercritical parameters of steam for different options of its loading. The equivalent lifespan exceeds the turbine's assigned lifespan only provided daily shutdown of the power unit during the night off-peak time. We obtained the engineering and economical indices of the power unit operation for different loading regulation options in daily and weekly diagrams. We proved the change in the prime cost of electric power depending on the operation regimes and annual daily number of unloading (non-use) of the power unit's installed capacity. According to the calculation results, the prime cost of electric power for the assumed initial data varies from 11.3 cents/(kW h) in the basic regime of power unit operation (with an equivalent operation time of 166700 hours) to 15.5 cents/(kW h) in the regime with night and holiday shutdowns. The reduction of using the installed capacity of power unit at varying regimes from 3.5 to 11.9 hours per day can increase the prime cost of energy from 4.2 to 37.4%. Furthermore, repair and maintenance costs grow by 4.5% and by 3 times, respectively, in comparison with the basic regime. These results indicate the need to create special maneuverable equipment for working in the varying section of the electric load diagram.

  1. Cellular dynamics of memory B cell populations: IgM+ and IgG+ memory B cells persist indefinitely as quiescent cells1

    Science.gov (United States)

    Jones, Derek D.; Wilmore, Joel R.; Allman, David

    2015-01-01

    Despite their critical role in long-term immunity, the lifespan of individual memory B cells remains poorly defined. Using a tetracycline-regulated pulse-chase system, we measured population turnover rates and individual half-lives of pre-established antigen-induced immunoglobulin (Ig) class-switched and IgM-positive memory B cells over 402 days. Our results indicate that, once established, both IgG-positive and less frequent IgM-positive memory populations are exceptionally stable, with little evidence of attrition or cellular turnover. Indeed, the vast majority of cells in both pools exhibited half-lives that appear to exceed the lifespan of the mouse, contrasting dramatically with mature naïve B cells. These results indicate that recall antibody responses are mediated by stable pools of extremely long-lived cells, and suggest that antigen-experienced B cells employ remarkably efficient survival mechanisms. PMID:26438523

  2. A Course in Cellular Bioengineering.

    Science.gov (United States)

    Lauffenburger, Douglas A.

    1989-01-01

    Gives an overview of a course in chemical engineering entitled "Cellular Bioengineering," dealing with how chemical engineering principles can be applied to molecular cell biology. Topics used are listed and some key references are discussed. Listed are 85 references. (YP)

  3. Novel Materials for Cellular Nanosensors

    DEFF Research Database (Denmark)

    Sasso, Luigi

    The monitoring of cellular behavior is useful for the advancement of biomedical diagnostics, drug development and the understanding of a cell as the main unit of the human body. Micro- and nanotechnology allow for the creation of functional devices that enhance the study of cellular dynamics...... by providing platforms that offer biocompatible surfaces for the cell culturing in lab-on-chip devices integrated with optimized nanosensors with high specificities and sensitivities towards cellular analytes. In this project, novel materials were investigated with a focus on providing suitable surface...... modifications for electrochemical nanosensors for the detection of analytes released from cells. Two type of materials were investigated, each pertaining to the two different aspects of such devices: peptide nanostructures were studied for the creation of cellular sensing substrates that mimic in vivo surfaces...

  4. Energy Landscape of Cellular Networks

    Science.gov (United States)

    Wang, Jin

    2008-03-01

    Cellular Networks are in general quite robust and perform their biological functions against the environmental perturbations. Progresses have been made from experimental global screenings, topological and engineering studies. However, there are so far few studies of why the network should be robust and perform biological functions from global physical perspectives. In this work, we will explore the global properties of the network from physical perspectives. The aim of this work is to develop a conceptual framework and quantitative physical methods to study the global nature of the cellular network. The main conclusion of this presentation is that we uncovered the underlying energy landscape for several small cellular networks such as MAPK signal transduction network and gene regulatory networks, from the experimentally measured or inferred inherent chemical reaction rates. The underlying dynamics of these networks can show bi-stable as well as oscillatory behavior. The global shapes of the energy landscapes of the underlying cellular networks we have studied are robust against perturbations of the kinetic rates and environmental disturbances through noise. We derived a quantitative criterion for robustness of the network function from the underlying landscape. It provides a natural explanation of the robustness and stability of the network for performing biological functions. We believe the robust landscape is a global universal property for cellular networks. We believe the robust landscape is a quantitative realization of Darwinian principle of natural selection at the cellular network level. It may provide a novel algorithm for optimizing the network connections, which is crucial for the cellular network design and synthetic biology. Our approach is general and can be applied to other cellular networks.

  5. Mathematical Modeling of Cellular Metabolism.

    Science.gov (United States)

    Berndt, Nikolaus; Holzhütter, Hermann-Georg

    2016-01-01

    Cellular metabolism basically consists of the conversion of chemical compounds taken up from the extracellular environment into energy (conserved in energy-rich bonds of organic phosphates) and a wide array of organic molecules serving as catalysts (enzymes), information carriers (nucleic acids), and building blocks for cellular structures such as membranes or ribosomes. Metabolic modeling aims at the construction of mathematical representations of the cellular metabolism that can be used to calculate the concentration of cellular molecules and the rates of their mutual chemical interconversion in response to varying external conditions as, for example, hormonal stimuli or supply of essential nutrients. Based on such calculations, it is possible to quantify complex cellular functions as cellular growth, detoxification of drugs and xenobiotic compounds or synthesis of exported molecules. Depending on the specific questions to metabolism addressed, the methodological expertise of the researcher, and available experimental information, different conceptual frameworks have been established, allowing the usage of computational methods to condense experimental information from various layers of organization into (self-) consistent models. Here, we briefly outline the main conceptual frameworks that are currently exploited in metabolism research.

  6. Maintenance of cellular ATP level by caloric restriction correlates chronological survival of budding yeast

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Joon-Seok; Lee, Cheol-Koo, E-mail: cklee2005@korea.ac.kr

    2013-09-13

    Highlights: •CR decreases total ROS and mitochondrial superoxide during the chronological aging. •CR does not affect the levels of oxidative damage on protein and DNA. •CR contributes extension of chronological lifespan by maintenance of ATP level -- Abstract: The free radical theory of aging emphasizes cumulative oxidative damage in the genome and intracellular proteins due to reactive oxygen species (ROS), which is a major cause for aging. Caloric restriction (CR) has been known as a representative treatment that prevents aging; however, its mechanism of action remains elusive. Here, we show that CR extends the chronological lifespan (CLS) of budding yeast by maintaining cellular energy levels. CR reduced the generation of total ROS and mitochondrial superoxide; however, CR did not reduce the oxidative damage in proteins and DNA. Subsequently, calorie-restricted yeast had higher mitochondrial membrane potential (MMP), and it sustained consistent ATP levels during the process of chronological aging. Our results suggest that CR extends the survival of the chronologically aged cells by improving the efficiency of energy metabolism for the maintenance of the ATP level rather than reducing the global oxidative damage of proteins and DNA.

  7. Hierarchical Cellular Structures in High-Capacity Cellular Communication Systems

    CERN Document Server

    Jain, R K; Agrawal, N K

    2011-01-01

    In the prevailing cellular environment, it is important to provide the resources for the fluctuating traffic demand exactly in the place and at the time where and when they are needed. In this paper, we explored the ability of hierarchical cellular structures with inter layer reuse to increase the capacity of mobile communication network by applying total frequency hopping (T-FH) and adaptive frequency allocation (AFA) as a strategy to reuse the macro and micro cell resources without frequency planning in indoor pico cells [11]. The practical aspects for designing macro- micro cellular overlays in the existing big urban areas are also explained [4]. Femto cells are inducted in macro / micro / pico cells hierarchical structure to achieve the required QoS cost effectively.

  8. Moderately lower temperatures greatly extend the lifespan of Brachionus manjavacas (Rotifera): Thermodynamics or gene regulation?

    Science.gov (United States)

    Johnston, Rachel K; Snell, Terry W

    2016-06-01

    Environmental temperature greatly affects lifespan in a wide variety of animals, but the exact mechanisms underlying this effect are still largely unknown. A moderate temperature decrease from 22°C to 16°C extends the lifespan of the monogonont rotifer Brachionus manjavacas by up to 163%. Thermodynamic effects on metabolism contribute to this increase in longevity, but are not the only cause. When rotifers are exposed to 16°C for four days and then transfered to 22°C, they survive until day 13 at nearly identical rates as rotifers maintained at 16°C continuously. This persistence of the higher survival for nine days after transfer to 22°C suggests that low temperature exposure alters the expression of genes that affect the rate of aging. The relative persistence of the gene regulation effect suggests that it may play an even larger role in slowing aging than the thermodynamic effects. The life extending effects of these short-term low temperature treatments are largest when the exposure happens early in the life cycle, demonstrating the importance of early development. There is no advantage to lowering the temperature below 16°C to 11° or 5°C. Rotifers exposed to 16°C also displayed increased resistance to heat, starvation, oxidative and osmotic stress. Reproductive rates at 16°C were lower than those at 22°C, but because they reproduce longer, there is no significant change in the lifetime fecundity of females. To investigate which genes contribute to these effects, the expression of specific temperature sensing genes was knocked down using RNAi. Of 12 genes tested, RNAi knockdown of four eliminated the survival enhancing effects of the four-day cold treatment: TRP7, forkhead box C, Y-box factor, and ribosomal protein S6. This demonstrates that active gene regulation is an important factor in temperature mediated life extension, and that these particular genes play an integral role in these pathways. As a thermoresponsive sensor, TRP7 may be

  9. Soil Productive Lifespans: Rethinking Soil Sustainability for the 21st Century

    Science.gov (United States)

    Evans, Daniel

    2017-04-01

    The ability for humans to sustainably manage the natural resources on which they depend has been one of the existential challenges facing mankind since the dawn of civilisation. Given the demands from this century's unprecedented global population and the unremitting course of climatic change, that challenge has soared in intensity. Sustainability, in this context, refers to agricultural practices which meet the needs of the present without compromising the ability of future generations to meet their own needs. Ensuring sustainability is arguably of greatest importance when resources, such as soil, are non-renewable. However, there is as yet no tool to evaluate how sustainable conservation strategies are in the long-term. Up to now, many pedologists have assessed sustainability in binary terms, questioning whether management is sustainable or not. In truth, one can never determine whether a practice is ultimately sustainable because of the indefinite nature implied by "future generations". We suggest that a more useful assessment of sustainability for the 21st century should avoid binary questions and instead ask: how sustainable are soils? Indeed, how many future generations can soils provide for? Although the use of modelling is by no means a novelty for the discipline, there are very few holistic models that encompass the fluxes and dynamic relationships between both mass and quality concomitantly. We therefore propose a new conceptual framework - the Soil Productive Lifespan (SPL) - that employs empirically derived residence times of both soil mass and quality, together with pathways of environmental change, to forecast the length of time a soil profile can provide the critical functions. Although mass and quality are considered synergistically, the SPL model allows one to assess whether mass or quality alone presents the greatest limiting factor in the productive lifespans of soils. As a result, more targeted conservation strategies can be designed. Ultimately

  10. Handedness throughout the lifespan: Cross-sectional view on sex differences as asymmetries change

    Directory of Open Access Journals (Sweden)

    Mukundhan eSivagnanasunderam

    2015-01-01

    Full Text Available Manual asymmetries has been studied by many researchers, however contradictory findings still exist as to whether preferred manual asymmetries increases with age or do we become more ambidextrous. Recently it was shown that perhaps there is a third option, that there is no increase or decrease in laterality but rather preferred manual asymmetries remains consistent throughout adulthood. Another related finding is that females appear to have an advantage in some handedness tasks, such as the Grooved Pegboard. When a larger pegboard is used, sex differences may reverse as males may perform better when larger pegs and a larger trajectory are required. However, it is not fully understood if these sex differences arise from an early age and continue throughout life. Therefore we sought to explore sex differences in preferred hand dominance throughout the lifespan. In order to explore preferred hand dominance during the lifespan we examined 76 children (19 4 to 5 year olds, 12 female, M age = 4.73; 34 6 to 8 year olds, 12 female, M age = 6.97; 23 9 to 12 year olds, 14 female, M age = 10.83 in Experiment 1 and 35 healthy young right-handed adults (15 female, M age = 20.91 and 37 healthy older right-handed adults (20 female, M age = 72.3 in Experiment 2. Individuals were tested using a standard size (small and modified Grooved Pegboard (larger pegboard. Our study demonstrates that hand asymmetries are present early in life (children 4 to 5 years old at that these differences attenuate as a function of age until adulthood (Experiment 1. Furthermore, our results demonstrate that as we age (Experiment 2, asymmetries may increase (small and large pegboards, decrease (Annett, or stay the same (finger tapping. As well we demonstrated that the sex differences could not be entirely accounted for by hand size. Therefore, asymmetries as regard to the aging process, seems to be task specific which may account for the conflicting findings in research.

  11. Prognosis of Different Cellular Generations

    Directory of Open Access Journals (Sweden)

    Preetish Ranjan

    2013-04-01

    Full Text Available Technological advancement in mobile telephony from 1G to 3G, 4G and 5G has a very axiomatic fact that made an entire world a global village. The cellular system employs a different design approach and technology that most commercial radio and television system use. In the cellular system, the service area is divided into cells and a transmitter is designed to serve an individual cell. The system seeks to make efficient use of available channels by using low-power transmitters to allow frequency reuse at a smaller distance. Maximizing the number of times each channel can be reused in a given geographical area is the key to an efficient cellular system design. During the past three decades, the world has seen significant changes in telecommunications industry. There have been some remarkable aspects to the rapid growth in wireless communications, as seen by the large expansion in mobile systems. This paper focuses on “Past, Present & Future of Cellular Telephony” and some light has been thrown upon the technologies of the cellular systems, namely 1G, 2G, 2.5G, 3G and future generations like 4G and 5G systems as well.

  12. Continuum representations of cellular solids

    Energy Technology Data Exchange (ETDEWEB)

    Neilsen, M.K.

    1993-09-01

    Cellular materials consist of interconnected struts or plates which form cells. The struts or plates are constructed from a variety of metals, polymers, ceramics and wood products. Cellular materials are often used in impact limiters for shipping containers to protect the contents from accidental impact events. These materials exhibit a variety of complex behavior when subjected to crushing loads. This research focuses on the development of continuum representations of cellular solids that can be used in the finite element analysis of shipping container accidents. A significant portion of this work is the development of a new methodology to relate localized deformations to appropriate constitutive descriptions. This methodology provides the insight needed to select constitutive descriptions for cellular solids that capture the localized deformations that are observed experimentally. Constitutive relations are developed for two different cellular materials, aluminum honeycomb and polyurethane foam. These constitutive relations are based on plasticity and continuum damage theories. Plasticity is used to describe the permanent deformation exhibited by both aluminum honeycomb and polyurethane foam. Continuum damage is needed to capture the change in elastic parameters due to cracking of the polyurethane cell wall materials. The new constitutive description of polyurethane foam is implemented in both static and dynamic finite element codes, and analytical and numerical predictions are compared with available experimental data.

  13. Classifying cellular automata using grossone

    Science.gov (United States)

    D'Alotto, Louis

    2016-10-01

    This paper proposes an application of the Infinite Unit Axiom and grossone, introduced by Yaroslav Sergeyev (see [7] - [12]), to the development and classification of one and two-dimensional cellular automata. By the application of grossone, new and more precise nonarchimedean metrics on the space of definition for one and two-dimensional cellular automata are established. These new metrics allow us to do computations with infinitesimals. Hence configurations in the domain space of cellular automata can be infinitesimally close (but not equal). That is, they can agree at infinitely many places. Using the new metrics, open disks are defined and the number of points in each disk computed. The forward dynamics of a cellular automaton map are also studied by defined sets. It is also shown that using the Infinite Unit Axiom, the number of configurations that follow a given configuration, under the forward iterations of cellular automaton maps, can now be computed and hence a classification scheme developed based on this computation.

  14. The neurobiology of depression--revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms.

    Science.gov (United States)

    Albert, Paul R; Benkelfat, Chawki; Descarries, Laurent

    2012-09-05

    The serotonin (5-HT) hypothesis of depression dates from the 1960s. It originally postulated that a deficit in brain serotonin, corrected by antidepressant drugs, was the origin of the illness. Nowadays, it is generally accepted that recurring mood disorders are brain diseases resulting from the combination, to various degrees, of genetic and other biological as well as environmental factors, evolving through the lifespan. All areas of neuroscience, from genes to behaviour, molecules to mind, and experimental to clinical, are actively engaged in attempts at elucidating the pathophysiology of depression and the mechanisms underlying the efficacy of antidepressant treatments. This first of two special issues of Philosophical Transactions B seeks to provide an overview of current developments in the field, with an emphasis on cellular and molecular mechanisms, and how their unravelling opens new perspectives for future research.

  15. Influence of sex and stress exposure across the lifespan on endophenotypes of depression: focus on behavior, glucocorticoids and hippocampus

    Directory of Open Access Journals (Sweden)

    Aarthi Raksha Gobinath

    2015-01-01

    Full Text Available Sex differences exist in vulnerability, symptoms and treatment of many neuropsychiatric disorders. In this review we discuss both preclinical and clinical research that investigates how sex influences depression endophenotypes at the behavioral, neuroendocrine, and neural levels across the lifespan. Chronic exposure to stress is a risk factor for depression and we discuss how stress during the prenatal, postnatal, and adolescent periods differentially affects males and females depending on the method of stress and metric examined. Given that the integrity of the hippocampus is compromised in depression, we specifically focus on sex differences in how hippocampal plasticity is affected by stress and depression across the lifespan. In addition, we examine how female physiology predisposes depression in adulthood, specifically in postpartum and perimenopausal periods. Finally, we discuss the underrepresentation of women in both preclinical and clinical research and how this limits our understanding of sex differences in vulnerability, presentation, and treatment of depression.

  16. The free-radical damage theory: Accumulating evidence against a simple link of oxidative stress to ageing and lifespan.

    Science.gov (United States)

    Speakman, John R; Selman, Colin

    2011-04-01

    Recent work on a small European cave salamander (Proteus anguinus) has revealed that it has exceptional longevity, yet it appears to have unexceptional defences against oxidative damage. This paper comes at the end of a string of other studies that are calling into question the free-radical damage theory of ageing. This theory rose to prominence in the 1990s as the dominant theory for why we age and die. Despite substantial correlative evidence to support it, studies in the last five years have raised doubts over its importance. In particular, these include studies of mice with the major antioxidant genes knocked out (both singly and in combination), which show the expected elevation in oxidative damage but no impact on lifespan. Combined, these findings raise fundamental questions over whether the free-radical damage theory remains useful for understanding the ageing process, and variation in lifespan and life histories.

  17. Influence of sex and stress exposure across the lifespan on endophenotypes of depression: focus on behavior, glucocorticoids, and hippocampus

    Science.gov (United States)

    Gobinath, Aarthi R.; Mahmoud, Rand; Galea, Liisa A.M.

    2015-01-01

    Sex differences exist in vulnerability, symptoms, and treatment of many neuropsychiatric disorders. In this review, we discuss both preclinical and clinical research that investigates how sex influences depression endophenotypes at the behavioral, neuroendocrine, and neural levels across the lifespan. Chronic exposure to stress is a risk factor for depression and we discuss how stress during the prenatal, postnatal, and adolescent periods differentially affects males and females depending on the method of stress and metric examined. Given that the integrity of the hippocampus is compromised in depression, we specifically focus on sex differences in how hippocampal plasticity is affected by stress and depression across the lifespan. In addition, we examine how female physiology predisposes depression in adulthood, specifically in postpartum and perimenopausal periods. Finally, we discuss the underrepresentation of women in both preclinical and clinical research and how this limits our understanding of sex differences in vulnerability, presentation, and treatment of depression. PMID:25610363

  18. The alkaloid compound harmane increases the lifespan of Caenorhabditis elegans during bacterial infection, by modulating the nematode's innate immune response

    DEFF Research Database (Denmark)

    Jakobsen, Henrik; Bojer, Martin Saxtorph; Marinus, Martin G.

    2013-01-01

    The nematode Caenorhabditis elegans has in recent years been proven to be a powerful in vivo model for testing antimicrobial compounds. We report here that the alkaloid compound Harmane (2-methyl-β-carboline) increases the lifespan of nematodes infected with a human pathogen, the Shiga toxin......-producing Escherichia coli O157:H7 strain EDL933 and several other bacterial pathogens. This was shown to be unrelated to the weak antibiotic effect of Harmane. Using GFP-expressing E. coli EDL933, we showed that Harmane does not lower the colonization burden in the nematodes. We also found that the expression...... of the putative immune effector gene F35E12.5 was up-regulated in response to Harmane treatment. This indicates that Harmane stimulates the innate immune response of the nematode; thereby increasing its lifespan during bacterial infection. Expression of F35E12.5 is predominantly regulated through the p38 MAPK...

  19. Better Living through Chemistry: Caloric Restriction (CR) and CR Mimetics Alter Genome Function to Promote Increased Health and Lifespan

    Science.gov (United States)

    Gillespie, Zoe E.; Pickering, Joshua; Eskiw, Christopher H.

    2016-01-01

    Caloric restriction (CR), defined as decreased nutrient intake without causing malnutrition, has been documented to increase both health and lifespan across numerous organisms, including humans. Many drugs and other compounds naturally occurring in our diet (nutraceuticals) have been postulated to act as mimetics of caloric restriction, leading to a wave of research investigating the efficacy of these compounds in preventing age-related diseases and promoting healthier, longer lifespans. Although well studied at the biochemical level, there are still many unanswered questions about how CR and CR mimetics impact genome function and structure. Here we discuss how genome function and structure are influenced by CR and potential CR mimetics, including changes in gene expression profiles and epigenetic modifications and their potential to identify the genetic fountain of youth. PMID:27588026

  20. NAD(+) Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair.

    Science.gov (United States)

    Fang, Evandro Fei; Kassahun, Henok; Croteau, Deborah L; Scheibye-Knudsen, Morten; Marosi, Krisztina; Lu, Huiming; Shamanna, Raghavendra A; Kalyanasundaram, Sumana; Bollineni, Ravi Chand; Wilson, Mark A; Iser, Wendy B; Wollman, Bradley N; Morevati, Marya; Li, Jun; Kerr, Jesse S; Lu, Qiping; Waltz, Tyler B; Tian, Jane; Sinclair, David A; Mattson, Mark P; Nilsen, Hilde; Bohr, Vilhelm A

    2016-10-11

    Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive neurodegeneration and cerebellar ataxia. A-T is causally linked to defects in ATM, a master regulator of the response to and repair of DNA double-strand breaks. The molecular basis of cerebellar atrophy and neurodegeneration in A-T patients is unclear. Here we report and examine the significance of increased PARylation, low NAD(+), and mitochondrial dysfunction in ATM-deficient neurons, mice, and worms. Treatments that replenish intracellular NAD(+) reduce the severity of A-T neuropathology, normalize neuromuscular function, delay memory loss, and extend lifespan in both animal models. Mechanistically, treatments that increase intracellular NAD(+) also stimulate neuronal DNA repair and improve mitochondrial quality via mitophagy. This work links two major theories on aging, DNA damage accumulation, and mitochondrial dysfunction through nuclear DNA damage-induced nuclear-mitochondrial signaling, and demonstrates that they are important pathophysiological determinants in premature aging of A-T, pointing to therapeutic interventions. Published by Elsevier Inc.

  1. Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome.

    Directory of Open Access Journals (Sweden)

    Wilson C Fok

    Full Text Available Rapamycin was found to increase (11% to 16% the lifespan of male and female C57BL/6J mice most likely by reducing the increase in the hazard for mortality (i.e., the rate of aging term in the Gompertz mortality analysis. To identify the pathways that could be responsible for rapamycin's longevity effect, we analyzed the transcriptome of liver from 25-month-old male and female mice fed rapamycin starting at 4 months of age. Few changes (4,500 changed significantly in females. Using multidimensional scaling and heatmap analyses, the male mice fed rapamycin were found to segregate into two groups: one group that is almost identical to control males (Rapa-1 and a second group (Rapa-2 that shows a change in gene expression (>4,000 transcripts with more than 60% of the genes shared with female mice fed Rapa. Using ingenuity pathway analysis, 13 pathways were significantly altered in both Rapa-2 males and rapamycin-fed females with mitochondrial function as the most significantly changed pathway. Our findings show that rapamycin has a major effect on the transcriptome and point to several pathways that would likely impact the longevity.

  2. Lifespan of mountain ranges scaled by feedbacks between landsliding and erosion by rivers.

    Science.gov (United States)

    Egholm, David L; Knudsen, Mads F; Sandiford, Mike

    2013-06-27

    An important challenge in geomorphology is the reconciliation of the high fluvial incision rates observed in tectonically active mountain ranges with the long-term preservation of significant mountain-range relief in ancient, tectonically inactive orogenic belts. River bedrock erosion and sediment transport are widely recognized to be the principal controls on the lifespan of mountain ranges. But the factors controlling the rate of erosion and the reasons why they seem to vary significantly as a function of tectonic activity remain controversial. Here we use computational simulations to show that the key to understanding variations in the rate of erosion between tectonically active and inactive mountain ranges may relate to a bidirectional coupling between bedrock river incision and landslides. Whereas fluvial incision steepens surrounding hillslopes and increases landslide frequency, landsliding affects fluvial erosion rates in two fundamentally distinct ways. On the one hand, large landslides overwhelm the river transport capacity and cause upstream build up of sediment that protects the river bed from further erosion. On the other hand, in delivering abrasive agents to the streams, landslides help accelerate fluvial erosion. Our models illustrate how this coupling has fundamentally different implications for rates of fluvial incision in active and inactive mountain ranges. The coupling therefore provides a plausible physical explanation for the preservation of significant mountain-range relief in old orogenic belts, up to several hundred million years after tectonic activity has effectively ceased.

  3. How does male ritual behavior vary across the lifespan? An examination of Fijian kava ceremonies.

    Science.gov (United States)

    Shaver, John H; Sosis, Richard

    2014-03-01

    Ritual behaviors of some form exist in every society known to anthropologists. Despite this universality, we have little understanding of how ritual behavior varies within populations or across the lifespan, nor the determinants of this variation. Here we test hypotheses derived from life history theory by using behavioral observations and oral interview data concerning participant variation in Fijian kava-drinking ceremonies. We predicted that substantial variation in the frequency and duration of participation would result from (1) trade-offs with reproduction and (2) the intrinsic status differences between ritual participants. We demonstrate that when controlling for household composition, men with young offspring participated less frequently and exhibited greater variance in their time spent at ceremonies than men without young children. However, men with a larger number of total dependents in their household participated more frequently than those with fewer. Moreover, we found that men's ascribed rank, level of education, and reliance on wage labor all significantly predict their frequency of attendance. We also found that the number of dependents a man has in his household is positively correlated with total food production, and the amount of kava he cultivates. In general, these results suggest that ritual participation is part of an important strategy employed by Fijian men for both achieving status and developing social alliances. Variation in participation in kava ceremonies by Fijian men therefore reflects the constraints of their current life history condition and their inherited rank.

  4. Conceptualization of the Life-Span Development Theory: Relevance for Sexual and Reproductive Health in Ghana

    Directory of Open Access Journals (Sweden)

    Baba Musah Iddrisu

    2013-06-01

    Full Text Available Sexual and reproductive health issues continue to generate concerns in contemporarysociety because it is essential to individuals, couples and families, as well as the social andeconomic development of communities and nations. The concept of sexual andreproductive health (SRH provides a comprehensive and integrated approach to healthneeds related to sexuality and reproduction when viewed from the lens of lifespandevelopment theory. It is a public health concern, human rights issue and is indispensableto the attainment of the Millennium Development Goals because three out of the eightgoals are directly related to SRH, while the others have a close relationship with health.The 1994 International Conference on Population and Development in Cairo provided animpetus for program planners, family planning researchers, service providers, policymakers and other stakeholders to recognize the importance of SRH internationally.Nonetheless, the global situation depicts clear inequities between developed anddeveloping regions. Also, women bear the major share of the burden of sexual andreproductive ill health compared to men. It is essential to close these regional and gendergaps since SRH is vital to our quality of life, as other major aspects of health. This paper,which is an exploration of the literature, highlights the (a importance of SRH across thehuman lifespan, (b determinants of SRH in Ghana, and (c challenges associated withSRH issues in Ghana. Also, implications of SRH for public health education, policy,practice and research are discussed.

  5. Polyhydroxy fullerenes (fullerols or fullerenols: beneficial effects on growth and lifespan in diverse biological models.

    Directory of Open Access Journals (Sweden)

    Jie Gao

    Full Text Available Recent toxicological studies on carbon nanomaterials, including fullerenes, have led to concerns about their safety. Functionalized fullerenes, such as polyhydroxy fullerenes (PHF, fullerols, or fullerenols, have attracted particular attention due to their water solubility and toxicity. Here, we report surprisingly beneficial and/or specific effects of PHF on model organisms representing four kingdoms, including the green algae Pseudokirchneriella subcapitata, the plant Arabidopsis thaliana, the fungus Aspergillus niger, and the invertebrate Ceriodaphnia dubia. The results showed that PHF had no acute or chronic negative effects on the freshwater organisms. Conversely, PHF could surprisingly increase the algal culture density over controls at higher concentrations (i.e., 72% increase by 1 and 5 mg/L of PHF and extend the lifespan and stimulate the reproduction of Daphnia (e.g. about 38% by 20 mg/L of PHF. We also show that at certain PHF concentrations fungal growth can be enhanced and Arabidopsis thaliana seedlings exhibit longer hypocotyls, while other complex physiological processes remain unaffected. These findings may open new research fields in the potential applications of PHF, e.g., in biofuel production and aquaculture. These results will form the basis of further research into the mechanisms of growth stimulation and life extension by PHF.

  6. The 50s cliff: perceptuo-motor learning rates across the lifespan.

    Science.gov (United States)

    Coats, Rachel O; Wilson, Andrew D; Snapp-Childs, Winona; Fath, Aaron J; Bingham, Geoffrey P

    2014-01-01

    We recently found that older adults show reduced learning rates when learning a new pattern of coordinated rhythmic movement. The purpose of this study was to extend that finding by examining the performance of all ages across the lifespan from the 20 s through to the 80 s to determine how learning rates change with age. We tested whether adults could learn to produce a novel coordinated rhythmic movement (90° relative phase) in a visually guided unimanual task. We determined learning rates to quantify changes in learning with age and to determine at what ages the changes occur. We found, as before, that learning rates of participants in their 70 s and 80 s were half those of participants in their 20 s. We also found a gradual slow decline in learning rate with age until approximately age 50, when there was a sudden drop to a reduced learning rate for the 60 though 80 year olds. We discuss possible causes for the "50 s cliff" in perceptuo-motor learning rates and suggest that age related deficits in perception of complex motions may be the key to understanding this result.

  7. Effects of testosterone and 5alpha-dihydrotestosterone on luteal lifespan in dairy heifers.

    Science.gov (United States)

    Silvia, W J; Jacobs, A L; Hayes, S H

    1989-11-01

    Endogenous concentrations of testosterone increase approximately 7 d prior to estrus in cattle and goats. Inhibition of testosterone synthesis results in a delay of luteal regression in both species. The purpose of this experiment was to determine if treatment with testosterone or 5alpha-dihydrotestosterone (DHT), 2 to 6 d prior to the endogenous rise in testosterone, would result in premature luteal regression. Sixteen heifers were randomly assigned to one of three treatment groups: 1) Control (n = 6); 2) testosterone (100 mug, n = 5); or 3) DHT (100 mug, n = 5). Each heifer received a single injection of the appropriate steriod on Day 8, 9, 10, 11 or 12 post estrus. Jugular venous blood samples were collected at frequent intervals for 24 h to quantify testosterone, and then daily for 14 d to quantify progesterone. Concentrations of testosterone increased within 15 min of injection of testosterone, and reached a maximum at 30 min. Concentrations were maintained at > 2 ng/ml throughout the first 24 h after injection. Based on concentrations of progesterone, neither androgen had any effect on the lifespan of the corpus luteum or the level of luteal function.

  8. Oxygen availability strongly affects chronological lifespan and thermotolerance in batch cultures of Saccharomyces cerevisiae

    Science.gov (United States)

    Bisschops, Markus M.; Vos, Tim; Martínez-Moreno, Rubén; Cortés, Pilar T.; Pronk, Jack T.; Daran-Lapujade, Pascale

    2015-01-01

    Stationary-phase (SP) batch cultures of Saccharomyces cerevisiae, in which growth has been arrested by carbon-source depletion, are widely applied to study chronological lifespan, quiescence and SP-associated robustness. Based on this type of experiments, typically performed under aerobic conditions, several roles of oxygen in aging have been proposed. However, SP in anaerobic yeast cultures has not been investigated in detail. Here, we use the unique capability of S. cerevisiae to grow in the complete absence of oxygen to directly compare SP in aerobic and anaerobic bioreactor cultures. This comparison revealed strong positive effects of oxygen availability on adenylate energy charge, longevity and thermotolerance during SP. A low thermotolerance of anaerobic batch cultures was already evident during the exponential growth phase and, in contrast to the situation in aerobic cultures, was not substantially increased during transition into SP. A combination of physiological and transcriptome analysis showed that the slow post-diauxic growth phase on ethanol, which precedes SP in aerobic, but not in anaerobic cultures, endowed cells with the time and resources needed for inducing longevity and thermotolerance. When combined with literature data on acquisition of longevity and thermotolerance in retentostat cultures, the present study indicates that the fast transition from glucose excess to SP in anaerobic cultures precludes acquisition of longevity and thermotolerance. Moreover, this study demonstrates the importance of a preceding, calorie-restricted conditioning phase in the acquisition of longevity and stress tolerance in SP yeast cultures, irrespective of oxygen availability. PMID:28357268

  9. Calorie restriction-mediated replicative lifespan extension in yeast is non-cell autonomous.

    Directory of Open Access Journals (Sweden)

    Szu-Chieh Mei

    2015-01-01

    Full Text Available In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA, are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell.

  10. From children to adults: motor performance across the life-span.

    Directory of Open Access Journals (Sweden)

    Jonas S R Leversen

    Full Text Available The life-span approach to development provides a theoretical framework to examine the general principles of life-long development. This study aims to investigate motor performance across the life span. It also aims to investigate if the correlations between motor tasks increase with aging. A cross-sectional design was used to describe the effects of aging on motor performance across age groups representing individuals from childhood to young adult to old age. Five different motor tasks were used to study changes in motor performance within 338 participants (7-79 yrs. Results showed that motor performance increases from childhood (7-9 to young adulthood (19-25 and decreases from young adulthood (19-25 to old age (66-80. These results are mirroring results from cognitive research. Correlation increased with increasing age between two fine motor tasks and two gross motor tasks. We suggest that the findings might be explained, in part, by the structural changes that have been reported to occur in the developing and aging brain and that the theory of Neural Darwinism can be used as a framework to explain why these changes occur.

  11. Microglia across the lifespan: from origin to function in brain development, plasticity and cognition.

    Science.gov (United States)

    Tay, Tuan Leng; Savage, Julie C; Hui, Chin Wai; Bisht, Kanchan; Tremblay, Marie-Ève

    2017-03-15

    Microglia are the only immune cells that permanently reside in the central nervous system (CNS) alongside neurons and other types of glial cells. The past decade has witnessed a revolution in our understanding of their roles during normal physiological conditions. Cutting-edge techniques revealed that these resident immune cells are critical for proper brain development, actively maintain health in the mature brain, and rapidly adapt their function to physiological or pathophysiological needs. In this review, we highlight recent studies on microglial origin (from the embryonic yolk sac) and the factors regulating their differentiation and homeostasis upon brain invasion. Elegant experiments tracking microglia in the CNS allowed studies of their unique roles compared with other types of resident macrophages. Here we review the emerging roles of microglia in brain development, plasticity and cognition, and discuss the implications of the depletion or dysfunction of microglia for our understanding of disease pathogenesis. Immune activation, inflammation and various other conditions resulting in undesirable microglial activity at different stages of life could severely impair learning, memory and other essential cognitive functions. The diversity of microglial phenotypes across the lifespan, between compartments of the CNS, and sexes, as well as their crosstalk with the body and external environment, is also emphasised. Understanding what defines particular microglial phenotypes is of major importance for future development of innovative therapies controlling their effector functions, with consequences for cognition across chronic stress, ageing, neuropsychiatric and neurological diseases.

  12. Overexpression of a Drosophila homolog of apolipoprotein D leads to increased stress resistance and extended lifespan.

    Science.gov (United States)

    Walker, David W; Muffat, Julien; Rundel, Colin; Benzer, Seymour

    2006-04-01

    Increased Apolipoprotein D (ApoD) expression has been reported in various neurological disorders, including Alzheimer's disease, schizophrenia, and stroke, and in the aging brain . However, whether ApoD is toxic or a defense is unknown. In a screen to identify genes that protect Drosophila against acute oxidative stress, we isolated a fly homolog of ApoD, Glial Lazarillo (GLaz). In independent transgenic lines, overexpression of GLaz resulted in increased resistance to hyperoxia (100% O(2)) as well as a 29% extension of lifespan under normoxia. These flies also displayed marked improvements in climbing and walking ability after sublethal exposure to hyperoxia. Overexpression of Glaz also increased resistance to starvation without altering lipid or protein content. To determine whether GLaz might be important in protection against reperfusion injury, we subjected the flies to hypoxia, followed by recovery under normoxia. Overexpression of GLaz was protective against behavioral deficits caused in normal flies by this ischemia/reperfusion paradigm. This and the accompanying paper by Sanchez et al. (in this issue of Current Biology) are the first to manipulate the levels of an ApoD homolog in a model organism. Our data suggest that human ApoD may play a protective role and thus may constitute a therapeutic target to counteract certain neurological diseases.

  13. Types of strain among family members of individuals with autism spectrum disorder across the lifespan.

    Science.gov (United States)

    Shivers, Carolyn M; Krizova, Katarina; Lee, Gloria K

    2017-09-01

    Although increased caregiver strain is often found among family caregivers of individuals with autism spectrum disorder, it is still unclear as to how different types of strain relate to amount and types of caregiving across the lifespan. The present study examined different types of strain (i.e. subjective internalized strain, subjective externalized strain, and objective strain) and how such strain relates to the amount of caregiving responsibilities. Data was collected via online survey from a sample of 193 family caregivers of individuals with ASD from the United States, Canada, and the Republic of Ireland. Participants completed measures of strain and caregiving responsibilities, as well as coping, demographics, and services needed and received by the individual with ASD. Caregivers reported higher levels of objective strain than subjective, and caregiving responsibility was related to objective and subjective internalized strain. Coping style was strongly correlated with all types of strain, and unmet service needs were significantly related to objective and subjective internalized strain. Caregiving behaviors were only related to objective strain. The present results indicate that, although caregiving responsibility is related to objective and subjective internalized strain, the relationship is perhaps not as strong as the relationship between coping mechanisms and strain. Future research is needed to understand different types of strain and develop strategies to help caregivers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Immigration, language proficiency, and autobiographical memories: Lifespan distribution and second-language access.

    Science.gov (United States)

    Esposito, Alena G; Baker-Ward, Lynne

    2016-08-01

    This investigation examined two controversies in the autobiographical literature: how cross-language immigration affects the distribution of autobiographical memories across the lifespan and under what circumstances language-dependent recall is observed. Both Spanish/English bilingual immigrants and English monolingual non-immigrants participated in a cue word study, with the bilingual sample taking part in a within-subject language manipulation. The expected bump in the number of memories from early life was observed for non-immigrants but not immigrants, who reported more memories for events surrounding immigration. Aspects of the methodology addressed possible reasons for past discrepant findings. Language-dependent recall was influenced by second-language proficiency. Results were interpreted as evidence that bilinguals with high second-language proficiency, in contrast to those with lower second-language proficiency, access a single conceptual store through either language. The final multi-level model predicting language-dependent recall, including second-language proficiency, age of immigration, internal language, and cue word language, explained ¾ of the between-person variance and (1)/5 of the within-person variance. We arrive at two conclusions. First, major life transitions influence the distribution of memories. Second, concept representation across multiple languages follows a developmental model. In addition, the results underscore the importance of considering language experience in research involving memory reports.

  15. Oxygen availability strongly affects chronological lifespan and thermotolerance in batch cultures of Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Markus M.M. Bisschops

    2015-10-01

    Full Text Available Stationary-phase (SP batch cultures of Saccharomyces cerevisiae, in which growth has been arrested by carbon-source depletion, are widely applied to study chronological lifespan, quiescence and SP-associated robustness. Based on this type of experiments, typically performed under aerobic conditions, several roles of oxygen in aging have been proposed. However, SP in anaerobic yeast cultures has not been investigated in detail. Here, we use the unique capability of S. cerevisiae to grow in the complete absence of oxygen to directly compare SP in aerobic and anaerobic bioreactor cultures. This comparison revealed strong positive effects of oxygen availability on adenylate energy charge, longevity and thermotolerance during SP. A low thermotolerance of anaerobic batch cultures was already evident during the exponential growth phase and, in contrast to the situation in aerobic cultures, was not substantially increased during transition into SP. A combination of physiological and transcriptome analysis showed that the slow post-diauxic growth phase on ethanol, which precedes SP in aerobic, but not in anaerobic cultures, endowed cells with the time and resources needed for inducing longevity and thermotolerance. When combined with literature data on acquisition of longevity and thermotolerance in retentostat cultures, the present study indicates that the fast transition from glucose excess to SP in anaerobic cultures precludes acquisition of longevity and thermotolerance. Moreover, this study demonstrates the importance of a preceding, calorie-restricted conditioning phase in the acquisition of longevity and stress tolerance in SP yeast cultures, irrespective of oxygen availability.

  16. A lifespan MRI evaluation of ventricular enlargement in normal aging mice.

    Science.gov (United States)

    Chen, Chiao-Chi V; Tung, Yu-Ying; Chang, Chen

    2011-12-01

    Ventricular enlargement has been proposed as a structural biomarker for the progression of Alzheimer's disease (AD). This biomarker, established in human patients, needs to be translated to animals to facilitate drug development for the disease. However, ventricular enlargement is not exclusive to AD, since the ventricle size increases during normal aging. A longitudinal characterization of ventricular enlargement in normal aging in mice is therefore crucial before further evaluations of mouse models or neurodegenerative diseases associated to brain atrophy. To this end, ventricular enlargement in normal aging mice was characterized over the lifespan (i.e., 2 years). The results showed that the overall ventricle size increased with age, with the expansion beginning during the early life stages and continuing to old age. The reported data represent a biomarker benchmark for normal aging mice under unmodified conditions. This provides a foundation for evaluating the validity of AD mouse models or the effects of potential drugs. The considerable physiological ventricular enlargement during normal aging must be considered in related experiments.

  17. Atomic Bomb Survivors Life-Span Study: Insufficient Statistical Power to Select Radiation Carcinogenesis Model.

    Science.gov (United States)

    Socol, Yehoshua; Dobrzyński, Ludwik

    2015-01-01

    The atomic bomb survivors life-span study (LSS) is often claimed to support the linear no-threshold hypothesis (LNTH) of radiation carcinogenesis. This paper shows that this claim is baseless. The LSS data are equally or better described by an s-shaped dependence on radiation exposure with a threshold of about 0.3 Sievert (Sv) and saturation level at about 1.5 Sv. A Monte-Carlo simulation of possible LSS outcomes demonstrates that, given the weak statistical power, LSS cannot provide support for LNTH. Even if the LNTH is used at low dose and dose rates, its estimation of excess cancer mortality should be communicated as 2.5% per Sv, i.e., an increase of cancer mortality from about 20% spontaneous mortality to about 22.5% per Sv, which is about half of the usually cited value. The impact of the "neutron discrepancy problem" - the apparent difference between the calculated and measured values of neutron flux in Hiroshima - was studied and found to be marginal. Major revision of the radiation risk assessment paradigm is required.

  18. Rhesus monkeys show human-like changes in gaze following across the lifespan.

    Science.gov (United States)

    Rosati, Alexandra G; Arre, Alyssa M; Platt, Michael L; Santos, Laurie R

    2016-05-11

    Gaze following, or co-orienting with others, is a foundational skill for human social behaviour. The emergence of this capacity scaffolds critical human-specific abilities such as theory of mind and language. Non-human primates also follow others' gaze, but less is known about how the cognitive mechanisms supporting this behaviour develop over the lifespan. Here we experimentally tested gaze following in 481 semi-free-ranging rhesus macaques (Macaca mulatta) ranging from infancy to old age. We found that monkeys began to follow gaze in infancy and this response peaked in the juvenile period-suggesting that younger monkeys were especially attuned to gaze information, like humans. After sexual maturity, monkeys exhibited human-like sex differences in gaze following, with adult females showing more gaze following than males. Finally, older monkeys showed reduced propensity to follow gaze, just as older humans do. In a second study (n = 80), we confirmed that macaques exhibit similar baseline rates of looking upwards in a control condition, regardless of age. Our findings indicate that-despite important differences in human and non-human primate life-history characteristics and typical social experiences-monkeys undergo robust ontogenetic shifts in gaze following across early development, adulthood and ageing that are strikingly similar to those of humans.

  19. A gene-expression-based neural code for food abundance that modulates lifespan.

    Science.gov (United States)

    Entchev, Eugeni V; Patel, Dhaval S; Zhan, Mei; Steele, Andrew J; Lu, Hang; Ch'ng, QueeLim

    2015-05-12

    How the nervous system internally represents environmental food availability is poorly understood. Here, we show that quantitative information about food abundance is encoded by combinatorial neuron-specific gene-expression of conserved TGFβ and serotonin pathway components in Caenorhabditis elegans. Crosstalk and auto-regulation between these pathways alters the shape, dynamic range, and population variance of the gene-expression responses of daf-7 (TGFβ) and tph-1 (tryptophan hydroxylase) to food availability. These intricate regulatory features provide distinct mechanisms for TGFβ and serotonin signaling to tune the accuracy of this multi-neuron code: daf-7 primarily regulates gene-expression variability, while tph-1 primarily regulates the dynamic range of gene-expression responses. This code is functional because daf-7 and tph-1 mutations bidirectionally attenuate food level-dependent changes in lifespan. Our results reveal a neural code for food abundance and demonstrate that gene expression serves as an additional layer of information processing in the nervous system to control long-term physiology.

  20. Animal models in epigenetic research: institutional animal care and use committee considerations across the lifespan.

    Science.gov (United States)

    Harris, Craig

    2012-01-01

    The rapid expansion and evolution of epigenetics as a core scientific discipline have raised new questions about how endogenous and environmental factors can inform the mechanisms through which biological form and function are regulated. Existing and proposed animal models used for epigenetic research have targeted a myriad of health and disease endpoints that may be acute, chronic, and transgenerational in nature. Initiating events and outcomes may extend across the entire lifespan to elicit unanticipated phenotypes that are of particular concern to institutional animal care and use committees (IACUCs). The dynamics and plasticity of epigenetic mechanisms produce effects and consequences that are manifest differentially within discreet spatial and temporal contexts, including prenatal development, stem cells, assisted reproductive technologies, production of sexual dimorphisms, senescence, and others. Many dietary and nutritional interventions have also been shown to have a significant impact on biological functions and disease susceptibilities through altered epigenetic programming. The environmental, chemical, toxic, therapeutic, and psychosocial stressors used in animal studies to elicit epigenetic changes can become extreme and should raise IACUC concerns for the well-being and proper care of all research animals involved. Epigenetics research is rapidly becoming an integral part of the search for mechanisms in every major area of biomedical and behavioral research and will foster the continued development of new animal models. From the IACUC perspective, care must be taken to acknowledge the particular needs and concerns created by superimposition of epigenetic mechanisms over diverse fields of investigation to ensure the proper care and use of animals without impeding scientific progress.