Genetic manipulation of longevity-related genes as a tool to regulate yeast life span and metabolite production during winemaking

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Orozco Helena

2013-01-01

Full Text Available Abstract Background Yeast viability and vitality are essential for different industrial processes where the yeast Saccharomyces cerevisiae is used as a biotechnological tool. Therefore, the decline of yeast biological functions during aging may compromise their successful biotechnological use. Life span is controlled by a variety of molecular mechanisms, many of which are connected to stress tolerance and genomic stability, although the metabolic status of a cell has proven a main factor affecting its longevity. Acetic acid and ethanol accumulation shorten chronological life span (CLS, while glycerol extends it. Results Different age-related gene classes have been modified by deletion or overexpression to test their role in longevity and metabolism. Overexpression of histone deacetylase SIR2 extends CLS and reduces acetate production, while overexpression of SIR2 homolog HST3 shortens CLS, increases the ethanol level, and reduces acetic acid production. HST3 overexpression also enhances ethanol tolerance. Increasing tolerance to oxidative stress by superoxide dismutase SOD2 overexpression has only a moderate positive effect on CLS. CLS during grape juice fermentation has also been studied for mutants on several mRNA binding proteins that are regulators of gene expression at the posttranscriptional level; we found that NGR1 and UTH4 deletions decrease CLS, while PUF3 and PUB1 deletions increase it. Besides, the pub1Δ mutation increases glycerol production and blocks stress granule formation during grape juice fermentation. Surprisingly, factors relating to apoptosis, such as caspase Yca1 or apoptosis-inducing factor Aif1, play a positive role in yeast longevity during winemaking as their deletions shorten CLS. Conclusions Manipulation of regulators of gene expression at both transcriptional (i.e., sirtuins and posttranscriptional (i.e., mRNA binding protein Pub1 levels allows to modulate yeast life span during its biotechnological use. Due to

Modulating aging and longevity

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Rattan, Suresh

Provides information and an evaluation of a variety of approaches tried for modulating aging and longevity, including dietary supplementation with antioxidants, vitamins and hormones, genetic engineering, life-style alterations, and hormesis through mild stress. After decades of systematic collec....... The goal of research on ageing is not to increase human longevity regardless of the consequences, but to increase active longevity free from disability and functional dependence......Provides information and an evaluation of a variety of approaches tried for modulating aging and longevity, including dietary supplementation with antioxidants, vitamins and hormones, genetic engineering, life-style alterations, and hormesis through mild stress. After decades of systematic...... collection of data describing age-related changes in organisms, organs, tissues, cells and macromolecules, biogerontologists are now in a position to construct general principles of ageing and explore various possibilities of intervention using rational approaches. While not giving serious consideration...

Identification and functional analyses of genes regulating seed dormancy, longevity and germination

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Yazdanpanah, Farzaneh

2018-01-01

Fundamental knowledge about the processes affecting seed performance, including the regulation of germination, dormancy and longevity can provide insight to improve these traits, which is of economic importance for agricultural use and storage of seed crops. Accordingly, the objective of this

Broad spectrum detoxification: the major longevity assurance process regulated by insulin/IGF-1 signaling?

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Gems, David; McElwee, Joshua J

2005-03-01

Our recent survey of genes regulated by insulin/IGF-1 signaling (IIS) in Caenorhabditis elegans suggests a role for a number of gene classes in longevity assurance. Based on these findings, we propose a model for the biochemistry of longevity assurance and ageing, which is as follows. Ageing results from molecular damage from highly diverse endobiotic toxins. These are stochastic by-products of diverse metabolic processes, of which reactive oxygen species (ROS) are likely to be only one component. Our microarray analysis suggests a major role in longevity assurance of the phase 1, phase 2 detoxification system involving cytochrome P450 (CYP), short-chain dehydrogenase/reductase (SDR) and UDP-glucuronosyltransferase (UGT) enzymes. Unlike superoxide and hydrogen peroxide detoxification, this system is energetically costly, and requires the excretion from the cell of its products. Given such costs, its activity may be selected against, as predicted by the disposable soma theory. CYP and UGT enzymes target lipophilic molecular species; insufficient activity of this system is consistent with age-pigment (lipofuscin) accumulation during ageing. We suggest that IIS-regulated longevity assurance involves: (a) energetically costly detoxification and excretion of molecular rubbish, and (b) conservation of existing proteins via molecular chaperones. Given the emphasis in this theory on investment in cellular waste disposal, and on protein conservation, we have dubbed it the green theory.

The longevity gender gap

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Aviv, Abraham; Shay, Jerry; Christensen, Kaare

2005-01-01

In this Perspective, we focus on the greater longevity of women as compared with men. We propose that, like aging itself, the longevity gender gap is exceedingly complex and argue that it may arise from sex-related hormonal differences and from somatic cell selection that favors cells more...... resistant to the ravages of time. We discuss the interplay of these factors with telomere biology and oxidative stress and suggest that an explanation for the longevity gender gap may arise from a better understanding of the differences in telomere dynamics between men and women....

Characterization of the Hypothalamic-Pituitary-Adrenal-Axis in Familial Longevity under Resting Conditions

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Jansen, Steffy W; Roelfsema, Ferdinand; Akintola, Abimbola A

2015-01-01

OBJECTIVE: The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched...... for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity. Here, we compared 24-h plasma ACTH and serum cortisol concentration profiles and different aspects of the regulation...... of the HPA-axis in offspring from long-lived siblings, who are enriched for familial longevity and age-matched controls. DESIGN: Case-control study within the Leiden Longevity study cohort consisting of 20 middle-aged offspring of nonagenarian siblings (offspring) together with 18 partners (controls...

Dietary-Induced Signals That Activate the Gonadal Longevity Pathway during Development Regulate a Proteostasis Switch in Caenorhabditis elegans Adulthood

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Netta Shemesh

2017-08-01

Full Text Available Cell-non-autonomous signals dictate the functional state of cellular quality control systems, remodeling the ability of cells to cope with stress and maintain protein homeostasis (proteostasis. One highly regulated cell-non-autonomous switch controls proteostatic capacity in Caenorhabditis elegans adulthood. Signals from the reproductive system down-regulate cyto-protective pathways, unless countered by signals reporting on germline proliferation disruption. Here, we utilized dihomo-γ-linolenic acid (DGLA that depletes the C. elegans germline to ask when cell-non-autonomous signals from the reproductive system determine somatic proteostasis and whether such regulation is reversible. We found that diet supplementation of DGLA resulted in the maintenance of somatic proteostasis after the onset of reproduction. DGLA-dependent proteostasis remodeling was only effective if animals were exposed to DGLA during larval development. A short exposure of 16 h during the second to fourth larval stages was sufficient and required to maintain somatic proteostasis in adulthood but not to extend lifespan. The reproductive system was required for DGLA-dependent remodeling of proteostasis in adulthood, likely via DGLA-dependent disruption of germline stem cells. However, arachidonic acid (AA, a somatic regulator of this pathway that does not require the reproductive system, presented similar regulatory timing. Finally, we showed that DGLA- and AA-supplementation led to activation of the gonadal longevity pathway but presented differential regulatory timing. Proteostasis and stress response regulators, including hsf-1 and daf-16, were only activated if exposed to DGLA and AA during development, while other gonadal longevity factors did not show this regulatory timing. We propose that C. elegans determines its proteostatic fate during development and is committed to either reproduction, and thus present restricted proteostasis, or survival, and thus present robust

Dopa decarboxylase (Ddc) affects variation in Drosophila longevity.

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De Luca, Maria; Roshina, Nataliya V; Geiger-Thornsberry, Gretchen L; Lyman, Richard F; Pasyukova, Elena G; Mackay, Trudy F C

2003-08-01

Mutational analyses in model organisms have shown that genes affecting metabolism and stress resistance regulate life span, but the genes responsible for variation in longevity in natural populations are largely unidentified. Previously, we mapped quantitative trait loci (QTLs) affecting variation in longevity between two Drosophila melanogaster strains. Here, we show that the longevity QTL in the 36E;38B cytogenetic interval on chromosome 2 contains multiple closely linked QTLs, including the Dopa decarboxylase (Ddc) locus. Complementation tests to mutations show that Ddc is a positional candidate gene for life span in these strains. Linkage disequilibrium (LD) mapping in a sample of 173 alleles from a single population shows that three common molecular polymorphisms in Ddc account for 15.5% of the genetic contribution to variance in life span from chromosome 2. The polymorphisms are in strong LD, and the effects of the haplotypes on longevity suggest that the polymorphisms are maintained by balancing selection. DDC catalyzes the final step in the synthesis of the neurotransmitters, dopamine and serotonin. Thus, these data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in individual life span.

Stress responses during ageing: molecular pathways regulating protein homeostasis.

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Kyriakakis, Emmanouil; Princz, Andrea; Tavernarakis, Nektarios

2015-01-01

The ageing process is characterized by deterioration of physiological function accompanied by frailty and ageing-associated diseases. The most broadly and well-studied pathways influencing ageing are the insulin/insulin-like growth factor 1 signaling pathway and the dietary restriction pathway. Recent studies in diverse organisms have also delineated emerging pathways, which collectively or independently contribute to ageing. Among them the proteostatic-stress-response networks, inextricably affect normal ageing by maintaining or restoring protein homeostasis to preserve proper cellular and organismal function. In this chapter, we survey the involvement of heat stress and endoplasmic reticulum stress responses in the regulation of longevity, placing emphasis on the cross talk between different response mechanisms and their systemic effects. We further discuss novel insights relevant to the molecular pathways mediating these stress responses that may facilitate the development of innovative interventions targeting age-related pathologies such as diabetes, cancer, cardiovascular and neurodegenerative diseases.

Longevity and Stress Resistant Property of 6-Gingerol from Zingiber officinale Roscoe in Caenorhabditis elegans.

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Lee, Eun Byeol; Kim, Jun Hyeong; An, Chang Wan; Kim, Yeong Jee; Noh, Yun Jeong; Kim, Su Jin; Kim, Ju-Eun; Shrestha, Abinash Chandra; Ham, Ha-Neul; Leem, Jae-Yoon; Jo, Hyung-Kwon; Kim, Dae-Sung; Moon, Kwang Hyun; Lee, Jeong Ho; Jeong, Kyung Ok; Kim, Dae Keun

2018-03-14

In order to discover lifespan-extending compounds made from natural resources, activity-guided fractionation of Zingiber officinale Roscoe (Zingiberaceae) ethanol extract was performed using the Caenorhabditis elegans ( C. elegans ) model system. The compound 6-gingerol was isolated from the most active ethyl acetate soluble fraction, and showed potent longevity-promoting activity. It also elevated the survival rate of worms against stressful environment including thermal, osmotic, and oxidative conditions. Additionally, 6-gingerol elevated the antioxidant enzyme activities of C. elegans , and showed a dose-depend reduction of intracellular reactive oxygen species (ROS) accumulation in worms. Further studies demonstrated that the increased stress tolerance of 6-gingerol-mediated worms could result from the promotion of stress resistance proteins such as heat shock protein (HSP-16.2) and superoxide dismutase (SOD-3). The lipofuscin levels in 6-gingerol treated intestinal worms were decreased in comparison to the control group. No significant 6-gingerol-related changes, including growth, food intake, reproduction, and movement were noted. These results suggest that 6-gingerol exerted longevity-promoting activities independently of these factors and could extend the human lifespan.

A genome-wide scan reveals important roles of DNA methylation in human longevity by regulating age-related disease genes.

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Fu-Hui Xiao

Full Text Available It is recognized that genetic factors contribute to human longevity. Besides the hypothesis of existence of longevity genes, another suggests that a lower frequency of risk alleles decreases the incidence of age-related diseases in the long-lived people. However, the latter finds no support from recent genetic studies. Considering the crucial role of epigenetic modification in gene regulation, we then hypothesize that suppressing disease-related genes in longevity individuals is likely achieved by epigenetic modification, e.g. DNA methylation. To test this hypothesis, we investigated the genome-wide methylation profile in 4 Chinese female centenarians and 4 middle-aged controls using methyl-DNA immunoprecipitation sequencing. 626 differentially methylated regions (DMRs were observed between both groups. Interestingly, genes with these DMRs were enriched in age-related diseases, including type-2 diabetes, cardiovascular disease, stroke and Alzheimer's disease. This pattern remains rather stable after including methylomes of two white individuals. Further analyses suggest that the observed DMRs likely have functional roles in regulating disease-associated gene expressions, with some genes [e.g. caspase 3 (CASP3] being down-regulated whereas the others [i.e. interleukin 1 receptor, type 2 (IL1R2] up-regulated. Therefore, our study suggests that suppressing the disease-related genes via epigenetic modification is an important contributor to human longevity.

Stress biology and aging mechanisms: toward understanding the deep connection between adaptation to stress and longevity.

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Epel, Elissa S; Lithgow, Gordon J

2014-06-01

The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress ("hormetic stress"). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses ("toxic stress") and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e.g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease. © The Author 2014. 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.

The microRNA machinery regulates fasting-induced changes in gene expression and longevity in Caenorhabditis elegans.

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Kogure, Akiko; Uno, Masaharu; Ikeda, Takako; Nishida, Eisuke

2017-07-07

Intermittent fasting (IF) is a dietary restriction regimen that extends the lifespans of Caenorhabditis elegans and mammals by inducing changes in gene expression. However, how IF induces these changes and promotes longevity remains unclear. One proposed mechanism involves gene regulation by microRNAs (miRNAs), small non-coding RNAs (∼22 nucleotides) that repress gene expression and whose expression can be altered by fasting. To test this proposition, we examined the role of the miRNA machinery in fasting-induced transcriptional changes and longevity in C. elegans We revealed that fasting up-regulated the expression of the miRNA-induced silencing complex (miRISC) components, including Argonaute and GW182, and the miRNA-processing enzyme DRSH-1 (the ortholog of the Drosophila Drosha enzyme). Our lifespan measurements demonstrated that IF-induced longevity was suppressed by knock-out or knockdown of miRISC components and was completely inhibited by drsh-1 ablation. Remarkably, drsh-1 ablation inhibited the fasting-induced changes in the expression of the target genes of DAF-16, the insulin/IGF-1 signaling effector in C. elegans Fasting-induced transcriptome alterations were substantially and modestly suppressed in the drsh-1 null mutant and the null mutant of ain-1 , a gene encoding GW182, respectively. Moreover, miRNA array analyses revealed that the expression levels of numerous miRNAs changed after 2 days of fasting. These results indicate that components of the miRNA machinery, especially the miRNA-processing enzyme DRSH-1, play an important role in mediating IF-induced longevity via the regulation of fasting-induced changes in gene expression. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Transaldolase inhibition impairs mitochondrial respiration and induces a starvation-like longevity response in Caenorhabditis elegans.

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Christopher F Bennett

2017-03-01

Full Text Available Mitochondrial dysfunction can increase oxidative stress and extend lifespan in Caenorhabditis elegans. Homeostatic mechanisms exist to cope with disruptions to mitochondrial function that promote cellular health and organismal longevity. Previously, we determined that decreased expression of the cytosolic pentose phosphate pathway (PPP enzyme transaldolase activates the mitochondrial unfolded protein response (UPRmt and extends lifespan. Here we report that transaldolase (tald-1 deficiency impairs mitochondrial function in vivo, as evidenced by altered mitochondrial morphology, decreased respiration, and increased cellular H2O2 levels. Lifespan extension from knockdown of tald-1 is associated with an oxidative stress response involving p38 and c-Jun N-terminal kinase (JNK MAPKs and a starvation-like response regulated by the transcription factor EB (TFEB homolog HLH-30. The latter response promotes autophagy and increases expression of the flavin-containing monooxygenase 2 (fmo-2. We conclude that cytosolic redox established through the PPP is a key regulator of mitochondrial function and defines a new mechanism for mitochondrial regulation of longevity.

A combination of genomic approaches reveals the role of FOXO1a in regulating an oxidative stress response pathway.

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Paola de Candia

2008-02-01

Full Text Available While many of the phenotypic differences between human and chimpanzee may result from changes in gene regulation, only a handful of functionally important regulatory differences are currently known. As a first step towards identifying transcriptional pathways that have been remodeled in the human lineage, we focused on a transcription factor, FOXO1a, which we had previously found to be up-regulated in the human liver compared to that of three other primate species. We concentrated on this gene because of its known role in the regulation of metabolism and in longevity.Using a combination of expression profiling following siRNA knockdown and chromatin immunoprecipitation in a human liver cell line, we identified eight novel direct transcriptional targets of FOXO1a. This set includes the gene for thioredoxin-interacting protein (TXNIP, the expression of which is directly repressed by FOXO1a. The thioredoxin-interacting protein is known to inhibit the reducing activity of thioredoxin (TRX, thereby hindering the cellular response to oxidative stress and affecting life span.Our results provide an explanation for the repeated observations that differences in the regulation of FOXO transcription factors affect longevity. Moreover, we found that TXNIP is down-regulated in human compared to chimpanzee, consistent with the up-regulation of its direct repressor FOXO1a in humans, and with differences in longevity between the two species.

PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated development and longevity.

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Tepper, Ronald G; Ashraf, Jasmine; Kaletsky, Rachel; Kleemann, Gunnar; Murphy, Coleen T; Bussemaker, Harmen J

2013-08-01

Reduced insulin/IGF-1-like signaling (IIS) extends C. elegans lifespan by upregulating stress response (class I) and downregulating other (class II) genes through a mechanism that depends on the conserved transcription factor DAF-16/FOXO. By integrating genome-wide mRNA expression responsiveness to DAF-16 with genome-wide in vivo binding data for a compendium of transcription factors, we discovered that PQM-1 is the elusive transcriptional activator that directly controls development (class II) genes by binding to the DAF-16-associated element (DAE). DAF-16 directly regulates class I genes only, through the DAF-16-binding element (DBE). Loss of PQM-1 suppresses daf-2 longevity and further slows development. Surprisingly, the nuclear localization of PQM-1 and DAF-16 is controlled by IIS in opposite ways and was also found to be mutually antagonistic. We observe progressive loss of nuclear PQM-1 with age, explaining declining expression of PQM-1 targets. Together, our data suggest an elegant mechanism for balancing stress response and development. Copyright © 2013 Elsevier Inc. All rights reserved.

The Role of Oxidative Stress in the Longevity and Insecticide Resistance Phenotype of the Major Malaria Vectors Anopheles arabiensis and Anopheles funestus.

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Oliver, Shüné V; Brooke, Basil D

2016-01-01

Oxidative stress plays numerous biological roles, both functional and pathological. The role of oxidative stress in various epidemiologically relevant biological traits in Anopheles mosquitoes is not well established. In this study, the effects of oxidative stress on the longevity and insecticide resistance phenotype in the major malaria vector species An. arabiensis and An. funestus were examined. Responses to dietary copper sulphate and hydrogen peroxide were used as proxies for the oxidative stress phenotype by determining the effect of copper on longevity and hydrogen peroxide lethal dose. Glutathione peroxidase and catalase activities were determined colorimetrically. Oxidative burden was quantified as protein carbonyl content. Changes in insecticide resistance phenotype were monitored by WHO bioassay. Insecticide resistant individuals showed an increased capacity for coping with oxidative stress, mediated by increased glutathione peroxidase and catalase activity. This effect was observed in both species, as well as in laboratory strains and F1 individuals derived from wild-caught An. funestus mothers. Phenotypic capacity for coping with oxidative stress was greatest in strains with elevated Cytochrome P450 activity. Synergism of oxidative stress defence enzymes by dietary supplementation with haematin, 3-Amino-1, 2, 4-triazole and Sodium diethyldithiocarbamate significantly increased pyrethroid-induced mortality in An. arabiensis and An. funestus. It is therefore concluded that defence against oxidative stress underlies the augmentation of the insecticide resistance phenotype associated with multiple blood-feeding. This is because multiple blood-feeding ultimately leads to a reduction of oxidative stress in insecticide resistant females, and also reduces the oxidative burden induced by DDT and pyrethroids, by inducing increased glutathione peroxidase activity. This study highlights the importance of oxidative stress in the longevity and insecticide resistance

The Role of Oxidative Stress in the Longevity and Insecticide Resistance Phenotype of the Major Malaria Vectors Anopheles arabiensis and Anopheles funestus.

Directory of Open Access Journals (Sweden)

Shüné V Oliver

Full Text Available Oxidative stress plays numerous biological roles, both functional and pathological. The role of oxidative stress in various epidemiologically relevant biological traits in Anopheles mosquitoes is not well established. In this study, the effects of oxidative stress on the longevity and insecticide resistance phenotype in the major malaria vector species An. arabiensis and An. funestus were examined. Responses to dietary copper sulphate and hydrogen peroxide were used as proxies for the oxidative stress phenotype by determining the effect of copper on longevity and hydrogen peroxide lethal dose. Glutathione peroxidase and catalase activities were determined colorimetrically. Oxidative burden was quantified as protein carbonyl content. Changes in insecticide resistance phenotype were monitored by WHO bioassay. Insecticide resistant individuals showed an increased capacity for coping with oxidative stress, mediated by increased glutathione peroxidase and catalase activity. This effect was observed in both species, as well as in laboratory strains and F1 individuals derived from wild-caught An. funestus mothers. Phenotypic capacity for coping with oxidative stress was greatest in strains with elevated Cytochrome P450 activity. Synergism of oxidative stress defence enzymes by dietary supplementation with haematin, 3-Amino-1, 2, 4-triazole and Sodium diethyldithiocarbamate significantly increased pyrethroid-induced mortality in An. arabiensis and An. funestus. It is therefore concluded that defence against oxidative stress underlies the augmentation of the insecticide resistance phenotype associated with multiple blood-feeding. This is because multiple blood-feeding ultimately leads to a reduction of oxidative stress in insecticide resistant females, and also reduces the oxidative burden induced by DDT and pyrethroids, by inducing increased glutathione peroxidase activity. This study highlights the importance of oxidative stress in the longevity and

PDP-1 links the TGF-β and IIS pathways to regulate longevity, development, and metabolism.

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Sri Devi Narasimhan

2011-04-01

Full Text Available The insulin/IGF-1 signaling (IIS pathway is a conserved regulator of longevity, development, and metabolism. In Caenorhabditis elegans IIS involves activation of DAF-2 (insulin/IGF-1 receptor tyrosine kinase, AGE-1 (PI 3-kinase, and additional downstream serine/threonine kinases that ultimately phosphorylate and negatively regulate the single FOXO transcription factor homolog DAF-16. Phosphatases help to maintain cellular signaling homeostasis by counterbalancing kinase activity. However, few phosphatases have been identified that negatively regulate the IIS pathway. Here we identify and characterize pdp-1 as a novel negative modulator of the IIS pathway. We show that PDP-1 regulates multiple outputs of IIS such as longevity, fat storage, and dauer diapause. In addition, PDP-1 promotes DAF-16 nuclear localization and transcriptional activity. Interestingly, genetic epistasis analyses place PDP-1 in the DAF-7/TGF-β signaling pathway, at the level of the R-SMAD proteins DAF-14 and DAF-8. Further investigation into how a component of TGF-β signaling affects multiple outputs of IIS/DAF-16, revealed extensive crosstalk between these two well-conserved signaling pathways. We find that PDP-1 modulates the expression of several insulin genes that are likely to feed into the IIS pathway to regulate DAF-16 activity. Importantly, dysregulation of IIS and TGF-β signaling has been implicated in diseases such as Type 2 Diabetes, obesity, and cancer. Our results may provide a new perspective in understanding of the regulation of these pathways under normal conditions and in the context of disease.

Mitonuclear protein imbalance as a conserved longevity mechanism

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Houtkooper, Riekelt H.; Mouchiroud, Laurent; Ryu, Dongryeol; Moullan, Norman; Katsyuba, Elena; Knott, Graham; Williams, Robert W.; Auwerx, Johan

2013-01-01

Longevity is regulated by a network of closely linked metabolic systems. We used a combination of mouse population genetics and RNA interference in Caenorhabditis elegans to identify mitochondrial ribosomal protein S5 (Mrps5) and other mitochondrial ribosomal proteins as metabolic and longevity

Stressed-induced TMEM135 protein is part of a conserved genetic network involved in fat storage and longevity regulation in Caenorhabditis elegans.

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Vernat J Exil

2010-12-01

Full Text Available Disorders of mitochondrial fat metabolism lead to sudden death in infants and children. Although survival is possible, the underlying molecular mechanisms which enable this outcome have not yet been clearly identified. Here we describe a conserved genetic network linking disorders of mitochondrial fat metabolism in mice to mechanisms of fat storage and survival in Caenorhabditis elegans (C. elegans. We have previously documented a mouse model of mitochondrial very-long chain acyl-CoA dehydrogenase (VLCAD deficiency. We originally reported that the mice survived birth, but, upon exposure to cold and fasting stresses, these mice developed cardiac dysfunction, which greatly reduced survival. We used cDNA microarrays to outline the induction of several markers of lipid metabolism in the heart at birth in surviving mice. We hypothesized that the induction of fat metabolism genes in the heart at birth is part of a regulatory feedback circuit that plays a critical role in survival. The present study uses a dual approach employing both C57BL/6 mice and the nematode, C. elegans, to focus on TMEM135, a conserved protein which we have found to be upregulated 4.3 (±0.14-fold in VLCAD-deficient mice at birth. Our studies have demonstrated that TMEM135 is highly expressed in mitochondria and in fat-loaded tissues in the mouse. Further, when fasting and cold stresses were introduced to mice, we observed 3.25 (±0.03- and 8.2 (±0.31-fold increases in TMEM135 expression in the heart, respectively. Additionally, we found that deletion of the tmem135 orthologue in C. elegans caused a 41.8% (±2.8% reduction in fat stores, a reduction in mitochondrial action potential and decreased longevity of the worm. In stark contrast, C. elegans transgenic animals overexpressing TMEM-135 exhibited increased longevity upon exposure to cold stress. Based on these results, we propose that TMEM135 integrates biological processes involving fat metabolism and energy expenditure in

Crosstalk between mitochondrial stress signals regulates yeast chronological lifespan.

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Schroeder, Elizabeth A; Shadel, Gerald S

2014-01-01

Mitochondrial DNA (mtDNA) exists in multiple copies per cell and is essential for oxidative phosphorylation. Depleted or mutated mtDNA promotes numerous human diseases and may contribute to aging. Reduced TORC1 signaling in the budding yeast, Saccharomyces cerevisiae, extends chronological lifespan (CLS) in part by generating a mitochondrial ROS (mtROS) signal that epigenetically alters nuclear gene expression. To address the potential requirement for mtDNA maintenance in this response, we analyzed strains lacking the mitochondrial base-excision repair enzyme Ntg1p. Extension of CLS by mtROS signaling and reduced TORC1 activity, but not caloric restriction, was abrogated in ntg1Δ strains that exhibited mtDNA depletion without defects in respiration. The DNA damage response (DDR) kinase Rad53p, which transduces pro-longevity mtROS signals, is also activated in ntg1Δ strains. Restoring mtDNA copy number alleviated Rad53p activation and re-established CLS extension following mtROS signaling, indicating that Rad53p senses mtDNA depletion directly. Finally, DDR kinases regulate nucleus-mitochondria localization dynamics of Ntg1p. From these results, we conclude that the DDR pathway senses and may regulate Ntg1p-dependent mtDNA stability. Furthermore, Rad53p senses multiple mitochondrial stresses in a hierarchical manner to elicit specific physiological outcomes, exemplified by mtDNA depletion overriding the ability of Rad53p to transduce an adaptive mtROS longevity signal. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Developmental stability, age at onset of foraging and longevity of Africanized honey bees (Apis mellifera L.) under heat stress (Hymenoptera: Apidae).

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Medina, Rubén G; Paxton, Robert J; De Luna, Efraín; Fleites-Ayil, Fernando A; Medina Medina, Luis A; Quezada-Euán, José Javier G

2018-05-01

Beekeeping with the western honey bee (Apis mellifera) is important in tropical regions but scant information is available on the possible consequences of global warming for tropical beekeeping. We evaluated the effect of heat stress on developmental stability, the age at onset of foraging (AOF) and longevity in Africanized honey bees (AHBs) in the Yucatan Peninsula of Mexico, one of the main honey producing areas in the Neotropics, where high temperatures occur in spring and summer. To do so, we reared worker AHB pupae under a fluctuating temperature regime, simulating current tropical heatwaves, with a high temperature peak of 40.0 °C for 1 h daily across six days, and compared them to control pupae reared at stable temperatures of 34.0-35.5 °C. Heat stress did not markedly affect overall body size, though the forewing of heat-stressed bees was slightly shorter than controls. However, bees reared under heat stress showed significantly greater fluctuating asymmetry (FA) in forewing shape. Heat stress also decreased AOF and reduced longevity. Our results show that changes occur in the phenotype and behavior of honey bees under heat stress, with potential consequences for colony fitness. Copyright © 2018 Elsevier Ltd. All rights reserved.

Loss of Nat4 and its associated histone H4 N-terminal acetylation mediates calorie restriction-induced longevity.

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Molina-Serrano, Diego; Schiza, Vassia; Demosthenous, Christis; Stavrou, Emmanouil; Oppelt, Jan; Kyriakou, Dimitris; Liu, Wei; Zisser, Gertrude; Bergler, Helmut; Dang, Weiwei; Kirmizis, Antonis

2016-12-01

Changes in histone modifications are an attractive model through which environmental signals, such as diet, could be integrated in the cell for regulating its lifespan. However, evidence linking dietary interventions with specific alterations in histone modifications that subsequently affect lifespan remains elusive. We show here that deletion of histone N-alpha-terminal acetyltransferase Nat4 and loss of its associated H4 N-terminal acetylation (N-acH4) extend yeast replicative lifespan. Notably, nat4Δ-induced longevity is epistatic to the effects of calorie restriction (CR). Consistent with this, (i) Nat4 expression is downregulated and the levels of N-acH4 within chromatin are reduced upon CR, (ii) constitutive expression of Nat4 and maintenance of N-acH4 levels reduces the extension of lifespan mediated by CR, and (iii) transcriptome analysis indicates that nat4Δ largely mimics the effects of CR, especially in the induction of stress-response genes. We further show that nicotinamidase Pnc1, which is typically upregulated under CR, is required for nat4Δ-mediated longevity. Collectively, these findings establish histone N-acH4 as a regulator of cellular lifespan that links CR to increased stress resistance and longevity. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Dietary Resveratrol Does Not Affect Life Span, Body Composition, Stress Response, and Longevity-Related Gene Expression in Drosophila melanogaster.

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Staats, Stefanie; Wagner, Anika E; Kowalewski, Bianca; Rieck, Florian T; Soukup, Sebastian T; Kulling, Sabine E; Rimbach, Gerald

2018-01-11

In this study, we tested the effect of the stilbene resveratrol on life span, body composition, locomotor activity, stress response, and the expression of genes encoding proteins centrally involved in ageing pathways in the model organism Drosophila melanogaster . Male and female w 1118 D. melanogaster were fed diets based on sucrose, corn meal, and yeast. Flies either received a control diet or a diet supplemented with 500 µmol/L resveratrol. Dietary resveratrol did not affect mean, median, and maximal life span of male and female flies. Furthermore, body composition remained largely unchanged following the resveratrol supplementation. Locomotor activity, as determined by the climbing index, was not significantly different between control and resveratrol-supplemented flies. Resveratrol-fed flies did not exhibit an improved stress response towards hydrogen peroxide as compared to controls. Resveratrol did not change mRNA steady levels of antioxidant ( catalase , glutathione-S-transferase , NADH dehydrogenase , glutathione peroxidase , superoxide dismutase 2 ) and longevity-related genes, including sirtuin 2 , spargel , and I'm Not Dead Yet . Collectively, present data suggest that resveratrol does not affect life span, body composition, locomotor activity, stress response, and longevity-associated gene expression in w 1118 D. melanogaster .

Dietary Resveratrol Does Not Affect Life Span, Body Composition, Stress Response, and Longevity-Related Gene Expression in Drosophila melanogaster

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Stefanie Staats

2018-01-01

Full Text Available In this study, we tested the effect of the stilbene resveratrol on life span, body composition, locomotor activity, stress response, and the expression of genes encoding proteins centrally involved in ageing pathways in the model organism Drosophila melanogaster. Male and female w1118 D. melanogaster were fed diets based on sucrose, corn meal, and yeast. Flies either received a control diet or a diet supplemented with 500 µmol/L resveratrol. Dietary resveratrol did not affect mean, median, and maximal life span of male and female flies. Furthermore, body composition remained largely unchanged following the resveratrol supplementation. Locomotor activity, as determined by the climbing index, was not significantly different between control and resveratrol-supplemented flies. Resveratrol-fed flies did not exhibit an improved stress response towards hydrogen peroxide as compared to controls. Resveratrol did not change mRNA steady levels of antioxidant (catalase, glutathione-S-transferase, NADH dehydrogenase, glutathione peroxidase, superoxide dismutase 2 and longevity-related genes, including sirtuin 2, spargel, and I’m Not Dead Yet. Collectively, present data suggest that resveratrol does not affect life span, body composition, locomotor activity, stress response, and longevity-associated gene expression in w1118 D. melanogaster.

A comparative cellular and molecular biology of longevity database.

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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.

The yeast PNC1 longevity gene is up-regulated by mRNA mistranslation.

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Raquel M Silva

Full Text Available Translation fidelity is critical for protein synthesis and to ensure correct cell functioning. Mutations in the protein synthesis machinery or environmental factors that increase synthesis of mistranslated proteins result in cell death and degeneration and are associated with neurodegenerative diseases, cancer and with an increasing number of mitochondrial disorders. Remarkably, mRNA mistranslation plays critical roles in the evolution of the genetic code, can be beneficial under stress conditions in yeast and in Escherichia coli and is an important source of peptides for MHC class I complex in dendritic cells. Despite this, its biology has been overlooked over the years due to technical difficulties in its detection and quantification. In order to shed new light on the biological relevance of mistranslation we have generated codon misreading in Saccharomyces cerevisiae using drugs and tRNA engineering methodologies. Surprisingly, such mistranslation up-regulated the longevity gene PNC1. Similar results were also obtained in cells grown in the presence of amino acid analogues that promote protein misfolding. The overall data showed that PNC1 is a biomarker of mRNA mistranslation and protein misfolding and that PNC1-GFP fusions can be used to monitor these two important biological phenomena in vivo in an easy manner, thus opening new avenues to understand their biological relevance.

Effects of Caenorhabditis elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16/FoxO regulation.

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Chen, Albert Tzong-Yang; Guo, Chunfang; Dumas, Kathleen J; Ashrafi, Kaveh; Hu, Patrick J

2013-10-01

The AGC family serine-threonine kinases Akt and Sgk are similar in primary amino acid sequence and in vitro substrate specificity, and both kinases are thought to directly phosphorylate and inhibit FoxO transcription factors. In the nematode Caenorhabditis elegans, it is well established that AKT-1 controls dauer arrest and lifespan by regulating the subcellular localization of the FoxO transcription factor DAF-16. SGK-1 is thought to act similarly to AKT-1 in lifespan control by phosphorylating and inhibiting the nuclear translocation of DAF-16/FoxO. Using sgk-1 null and gain-of-function mutants, we now provide multiple lines of evidence indicating that AKT-1 and SGK-1 influence C. elegans lifespan, stress resistance, and DAF-16/FoxO activity in fundamentally different ways. Whereas AKT-1 shortens lifespan, SGK-1 promotes longevity in a DAF-16-/FoxO-dependent manner. In contrast to AKT-1, which reduces resistance to multiple stresses, SGK-1 promotes resistance to oxidative stress and ultraviolet radiation but inhibits thermotolerance. Analysis of several DAF-16/FoxO target genes that are repressed by AKT-1 reveals that SGK-1 represses a subset of these genes while having little influence on the expression of others. Accordingly, unlike AKT-1, which promotes the cytoplasmic sequestration of DAF-16/FoxO, SGK-1 does not influence DAF-16/FoxO subcellular localization. Thus, in spite of their similar in vitro substrate specificities, Akt and Sgk influence longevity, stress resistance, and FoxO activity through distinct mechanisms in vivo. Our findings highlight the need for a re-evaluation of current paradigms of FoxO regulation by Sgk. © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity.

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Heimbucher, Thomas; Liu, Zheng; Bossard, Carine; McCloskey, Richard; Carrano, Andrea C; Riedel, Christian G; Tanasa, Bogdan; Klammt, Christian; Fonslow, Bryan R; Riera, Celine E; Lillemeier, Bjorn F; Kemphues, Kenneth; Yates, John R; O'Shea, Clodagh; Hunter, Tony; Dillin, Andrew

2015-07-07

FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and major determinants of aging in organisms ranging from worms to man. The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating enzyme MATH-33 as an essential DAF-16 regulator in IIS, which stabilizes active DAF-16 protein levels and, as a consequence, influences DAF-16 functions, such as metabolism, stress response, and longevity in C. elegans. MATH-33 associates with DAF-16 in cellulo and in vitro. MATH-33 functions as a deubiquitylase by actively removing ubiquitin moieties from DAF-16, thus counteracting the action of the RLE-1 E3-ubiquitin ligase. Our findings support a model in which MATH-33 promotes DAF-16 stability in response to decreased IIS by directly modulating its ubiquitylation state, suggesting that regulated oscillations in the stability of DAF-16 protein play an integral role in controlling processes such as metabolism and longevity. Copyright © 2015 Elsevier Inc. All rights reserved.

Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming.

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Paital, Biswaranjan; Panda, Sumana Kumari; Hati, Akshaya Kumar; Mohanty, Bobllina; Mohapatra, Manoj Kumar; Kanungo, Shyama; Chainy, Gagan Bihari Nityananda

2016-02-26

The world is projected to experience an approximate doubling of atmospheric CO2 concentration in the next decades. Rise in atmospheric CO2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 °C-5.8 °C by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species (ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress (OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to

Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming

Science.gov (United States)

Paital, Biswaranjan; Panda, Sumana Kumari; Hati, Akshaya Kumar; Mohanty, Bobllina; Mohapatra, Manoj Kumar; Kanungo, Shyama; Chainy, Gagan Bihari Nityananda

2016-01-01

The world is projected to experience an approximate doubling of atmospheric CO2 concentration in the next decades. Rise in atmospheric CO2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 °C-5.8 °C by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species (ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress (OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to

The longevity effect of echinacoside in Caenorhabditis elegans mediated through daf-16.

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Wang, Xue; Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

2015-01-01

Echinacoside (ECH), a natural polyphenolic compound, has been reported to possess important pharmacological activities. However, very little is known about whether or how ECH affects longevity in vivo. We have examined the effects of ECH on the life span and stress tolerance in Caenorhabditis elegans. Our studies demonstrate that the life span of wild-type worms could be extended in the presence of ECH. Furthermore, ECH was found to increase tolerance of worms to heat shock and oxidative stress, while not exerting any influence on pharyngeal pumping rate and progeny production. Our mechanistic studies indicate that supplementation of ECH increases the transcript level of daf-16. ECH treatment also modulates the nuclear localization and transcriptional activities of daf-16, thus fine tunes the expression of daf-16 target genes to promote longevity and increases stress response in C. elegans. Overall, this work reveals the longevity effect of ECH and elucidates the underpinning mechanisms.

Age-related and sex-specific differences in proteasome activity in individual Drosophila flies from wild type, longevity-selected and stress resistant strains

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Hansen, Tina Østergaard; Sarup, Pernille Merete; Loeschcke, Volker

2012-01-01

with that in C1 males. However, in longevity-selected LS1 flies the proteasome activity was significantly lower compared to C1 flies, but the sex differences were maintained to some extent. Five other stress resistant lines also had significantly reduced proteasome activity in both sexes. During ageing...... and that increased lifespan and stress resistance lead to a reduction in proteasome activity and recession of the age-related decline observed in control females....

Gene activation regresses atherosclerosis, promotes health, and enhances longevity

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Luoma Pauli V

2010-07-01

Full Text Available Abstract Background Lifestyle factors and pharmacological compounds activate genetic mechanisms that influence the development of atherosclerotic and other diseases. This article reviews studies on natural and pharmacological gene activation that promotes health and enhances longevity. Results Living habits including healthy diet and regular physical activity, and pharmacotherapy, upregulate genes encoding enzymes and apolipoprotein and ATP-binding cassette transporters, acting in metabolic processes that promote health and increase survival. Cytochrome P450-enzymes, physiological factors in maintaining cholesterol homeostasis, generate oxysterols for the elimination of surplus cholesterol. Hepatic CTP:phosphocholine cytidylyltransferase-α is an important regulator of plasma HDL-C level. Gene-activators produce plasma lipoprotein profile, high HDL-C, HDL2-C and HDL-C/cholesterol ratio, which is typical of low risk of atherosclerotic disease, and also of exceptional longevity together with reduced prevalence of cardiovascular, metabolic and other diseases. High HDL contributes to protection against inflammation, oxidation and thrombosis, and associates with good cognitive function in very old people. Avoiding unhealthy stress and managing it properly promotes health and increases life expectancy. Conclusions Healthy living habits and gene-activating xenobiotics upregulate mechanisms that produce lipoprotein pattern typical of very old people and enhance longevity. Lipoprotein metabolism and large HDL2 associate with the process of living a very long life. Major future goals for health promotion are the improving of commitment to both wise lifestyle choices and drug therapy, and further the developing of new and more effective and well tolerated drugs and treatments.

DAF-16/FOXO Transcription Factor in Aging and Longevity.

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Sun, Xiaojuan; Chen, Wei-Dong; Wang, Yan-Dong

2017-01-01

Aging is associated with age-related diseases and an increase susceptibility of cancer. Dissecting the molecular mechanisms that underlie aging and longevity would contribute to implications for preventing and treating the age-dependent diseases or cancers. Multiple signaling pathways such as the insulin/IGF-1 signaling pathway, TOR signaling, AMPK pathway, JNK pathway and germline signaling have been found to be involved in aging and longevity. And DAF-16/FOXO, as a key transcription factor, could integrate different signals from these pathways to modulate aging, and longevity via shuttling from cytoplasm to nucleus. Hence, understanding how DAF-16/FOXO functions will be pivotal to illustrate the processes of aging and longevity. Here, we summarized how DAF-16/FOXO receives signals from these pathways to affect aging and longevity. We also briefly discussed the transcriptional regulation and posttranslational modifications of DAF-16/FOXO, its co-factors as well as its potential downstream targets participating in lifespan according to the published data in C. elegans and in mammals, and in most cases, we may focus on the studies in C. elegans which has been considered to be a very good animal model for longevity research.

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

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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.

Indy mutations and Drosophila longevity

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Blanka eRogina

2013-04-01

Full Text Available Decreased expression of the fly and worm Indy genes extends longevity. The fly Indy gene and its mammalian homolog are transporters of Krebs cycle intermediates, with the highest rate of uptake for citrate. Cytosolic citrate has a role in energy regulation by affecting fatty acid synthesis and glycolysis. Fly, worm and mice Indy gene homologues are predominantly expressed in places important for intermediary metabolism. Consequently, decreased expression of Indy in fly and worm, and the removal of mIndy in mice exhibit changes associated with calorie restriction, such as decreased levels of lipids, changes in carbohydrate metabolism and increased mitochondrial biogenesis. Here we report that several Indy alleles in a diverse array of genetic backgrounds confer increased longevity.

A regulatory network-based approach dissects late maturation processes related to the acquisition of desiccation tolerance and longevity of Medicago truncatula seeds.

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Verdier, Jerome; Lalanne, David; Pelletier, Sandra; Torres-Jerez, Ivone; Righetti, Karima; Bandyopadhyay, Kaustav; Leprince, Olivier; Chatelain, Emilie; Vu, Benoit Ly; Gouzy, Jerome; Gamas, Pascal; Udvardi, Michael K; Buitink, Julia

2013-10-01

In seeds, desiccation tolerance (DT) and the ability to survive the dry state for prolonged periods of time (longevity) are two essential traits for seed quality that are consecutively acquired during maturation. Using transcriptomic and metabolomic profiling together with a conditional-dependent network of global transcription interactions, we dissected the maturation events from the end of seed filling to final maturation drying during the last 3 weeks of seed development in Medicago truncatula. The network revealed distinct coexpression modules related to the acquisition of DT, longevity, and pod abscission. The acquisition of DT and dormancy module was associated with abiotic stress response genes, including late embryogenesis abundant (LEA) genes. The longevity module was enriched in genes involved in RNA processing and translation. Concomitantly, LEA polypeptides accumulated, displaying an 18-d delayed accumulation compared with transcripts. During maturation, gulose and stachyose levels increased and correlated with longevity. A seed-specific network identified known and putative transcriptional regulators of DT, including ABSCISIC ACID-INSENSITIVE3 (MtABI3), MtABI4, MtABI5, and APETALA2/ ETHYLENE RESPONSE ELEMENT BINDING PROTEIN (AtAP2/EREBP) transcription factor as major hubs. These transcriptional activators were highly connected to LEA genes. Longevity genes were highly connected to two MtAP2/EREBP and two basic leucine zipper transcription factors. A heat shock factor was found at the transition of DT and longevity modules, connecting to both gene sets. Gain- and loss-of-function approaches of MtABI3 confirmed 80% of its predicted targets, thereby experimentally validating the network. This study captures the coordinated regulation of seed maturation and identifies distinct regulatory networks underlying the preparation for the dry and quiescent states.

Small nucleoli are a cellular hallmark of longevity.

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Tiku, Varnesh; Jain, Chirag; Raz, Yotam; Nakamura, Shuhei; Heestand, Bree; Liu, Wei; Späth, Martin; Suchiman, H Eka D; Müller, Roman-Ulrich; Slagboom, P Eline; Partridge, Linda; Antebi, Adam

2016-08-30

Animal lifespan is regulated by conserved metabolic signalling pathways and specific transcription factors, but whether these pathways affect common downstream mechanisms remains largely elusive. Here we show that NCL-1/TRIM2/Brat tumour suppressor extends lifespan and limits nucleolar size in the major C. elegans longevity pathways, as part of a convergent mechanism focused on the nucleolus. Long-lived animals representing distinct longevity pathways exhibit small nucleoli, and decreased expression of rRNA, ribosomal proteins, and the nucleolar protein fibrillarin, dependent on NCL-1. Knockdown of fibrillarin also reduces nucleolar size and extends lifespan. Among wildtype C. elegans, individual nucleolar size varies, but is highly predictive for longevity. Long-lived dietary restricted fruit flies and insulin-like-peptide mutants exhibit small nucleoli and fibrillarin expression, as do long-lived dietary restricted and IRS1 knockout mice. Furthermore, human muscle biopsies from individuals who underwent modest dietary restriction coupled with exercise also display small nucleoli. We suggest that small nucleoli are a cellular hallmark of longevity and metabolic health conserved across taxa.

What promotes longevity?

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Agnieszka Kujawska

2017-09-01

Full Text Available Introduction Scientists try to answer on the need of a long life with a full physical capability Nonagenarians, centenarians and their closest family members are characterized by a survival benefit throughout life. Moreover, twin studies of longevity suggest that around 25% of the variation in lifespan in developed countries may be inherited. It is therefore worth to examine the role of inter-relationship between nature vs nurture in longevity increment. Material and methods Articles in the EBSCO database have been analyzed using keywords: longevity, gene, behavior, environment. The available literature was subjectively selected. Then, the newest version of every paper was searched for. Results Restriction of calories as well as intake of desirable nutrients can promote adequate control of metabolic pathways and gene expression. APOE, DRD4, Paraoxonase 1, SIRT 3 and SIRT 5 genes can play an important role in longevity. Conclusions Genetic profile and environmental factors seems to both influence on the longevity. Relationships between genetic profile, behavior pattern, quality of life, years spent free from activity limitations and longevity should be examined, to be able to give a recipe on living a long and happy life.

Ageing Drosophila selected for longevity retain a young gene expression profile

DEFF Research Database (Denmark)

Sarup, Pernille Merete

and longevity selected lines. Among the latter genes we found a clear overrepresentation of genes involved in immune functions supporting the hypothesis of the life shortening effect of an overactive immune system (inflammaging). Eighty-four genes were differentially expressed at the same physiological age...... between control and longevity selected lines, and the overlap between the same chronological and physiological age gene lists counted 40 candidate genes for increased longevity. Among these were genes with functions in starvation resistance, a regulator of immune responses and several genes which have......  We have investigated how the gene-expression profile of longevity selected lines of Drosophila melanogaster differed from control lines in young, middle-aged and old male flies. 530 genes were differentially expressed between selected and control flies at the same chronological age. We used...

Environmental conditions can modulate the links among oxidative stress, age, and longevity.

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Marasco, Valeria; Stier, Antoine; Boner, Winnie; Griffiths, Kate; Heidinger, Britt; Monaghan, Pat

2017-06-01

Understanding the links between environmental conditions and longevity remains a major focus in biological research. We examined within-individual changes between early- and mid-adulthood in the circulating levels of four oxidative stress markers linked to ageing, using zebra finches (Taeniopygia guttata): a DNA damage product (8-hydroxy-2'-deoxyguanosine; 8-OHdG), protein carbonyls (PC), non-enzymatic antioxidant capacity (OXY), and superoxide dismutase activity (SOD). We further examined whether such within-individual changes differed among birds living under control (ad lib food) or more challenging environmental conditions (unpredictable food availability), having previously found that the latter increased corticosterone levels when food was absent but improved survival over a three year period. Our key findings were: (i) 8-OHdG and PC increased with age in both environments, with a higher increase in 8-OHdG in the challenging environment; (ii) SOD increased with age in the controls but not in the challenged birds, while the opposite was true for OXY; (iii) control birds with high levels of 8-OHdG died at a younger age, but this was not the case in challenged birds. Our data clearly show that while exposure to the potentially damaging effects of oxidative stress increases with age, environmental conditions can modulate the pace of this age-related change. Copyright © 2017 Elsevier B.V. All rights reserved.

RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans

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Seo, Mihwa; Seo, Keunhee; Hwang, Wooseon; Koo, Hee Jung; Hahm, Jeong-Hoon; Yang, Jae-Seong; Han, Seong Kyu; Hwang, Daehee; Kim, Sanguk; Jang, Sung Key; Lee, Yoontae; Nam, Hong Gil; Lee, Seung-Jae V.

2015-01-01

The homeostatic maintenance of the genomic DNA is crucial for regulating aging processes. However, the role of RNA homeostasis in aging processes remains unknown. RNA helicases are a large family of enzymes that regulate the biogenesis and homeostasis of RNA. However, the functional significance of RNA helicases in aging has not been explored. Here, we report that a large fraction of RNA helicases regulate the lifespan of Caenorhabditis elegans. In particular, we show that a DEAD-box RNA helicase, helicase 1 (HEL-1), promotes longevity by specifically activating the DAF-16/forkhead box O (FOXO) transcription factor signaling pathway. We find that HEL-1 is required for the longevity conferred by reduced insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) and is sufficient for extending lifespan. We further show that the expression of HEL-1 in the intestine and neurons contributes to longevity. HEL-1 enhances the induction of a large fraction of DAF-16 target genes. Thus, the RNA helicase HEL-1 appears to promote longevity in response to decreased IIS as a transcription coregulator of DAF-16. Because HEL-1 and IIS are evolutionarily well conserved, a similar mechanism for longevity regulation via an RNA helicase-dependent regulation of FOXO signaling may operate in mammals, including humans. PMID:26195740

In vitro cellular adaptations of indicators of longevity in response to treatment with serum collected from humans on calorie restricted diets.

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Joanne S Allard

2008-09-01

Full Text Available Calorie restriction (CR produces several health benefits and increases lifespan in many species. Studies suggest that alternate-day fasting (ADF and exercise can also provide these benefits. Whether CR results in lifespan extension in humans is not known and a direct investigation is not feasible. However, phenotypes observed in CR animals when compared to ad libitum fed (AL animals, including increased stress resistance and changes in protein expression, can be simulated in cells cultured with media supplemented with blood serum from CR and AL animals. Two pilot studies were undertaken to examine the effects of ADF and CR on indicators of health and longevity in humans. In this study, we used sera collected from those studies to culture human hepatoma cells and assessed the effects on growth, stress resistance and gene expression. Cells cultured in serum collected at the end of the dieting period were compared to cells cultured in serum collected at baseline (before the dieting period. Cells cultured in serum from ADF participants, showed a 20% increase in Sirt1 protein which correlated with reduced triglyceride levels. ADF serum also induced a 9% decrease in proliferation and a 25% increase in heat resistance. Cells cultured in serum from CR participants induced an increase in Sirt1 protein levels by 17% and a 30% increase in PGC-1alpha mRNA levels. This first in vitro study utilizing human serum to examine effects on markers of health and longevity in cultured cells resulted in increased stress resistance and an up-regulation of genes proposed to be indicators of increased longevity. The use of this in vitro technique may be helpful for predicting the potential of CR, ADF and other dietary manipulations to affect markers of longevity in humans.

Longevity Chance

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Timon Cheng-Yi Liu

2014-03-01

Full Text Available Britton Chance pursued his research and sailing until his death at age 97. His 100th anniversary was memorialized in this paper from longevity viewpoint. His lifelong work was very creative. His life was very colorful. His aging was very successful. He has lived a longevity.

Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the Shortened Longevity Induced by Graphene Oxide in Caenorhabditis elegans

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Zhao, Yunli; Yang, Ruilong; Rui, Qi; Wang, Dayong

2016-04-01

Graphene oxide (GO) has been shown to cause multiple toxicities in various organisms. However, the underlying molecular mechanisms for GO-induced shortened longevity are still unclear. We employed Caenorhabditis elegans to investigate the possible involvement of insulin signaling pathway in the control of GO toxicity and its underlying molecular mechanisms. Mutation of daf-2, age-1, akt-1, or akt-2 gene induced a resistant property of nematodes to GO toxicity, while mutation of daf-16 gene led to a susceptible property of nematodes to GO toxicity, suggesting that GO may dysregulate the functions of DAF-2/IGF-1 receptor, AGE-1, AKT-1 and AKT-2-mediated kinase cascade, and DAF-16/FOXO transcription factor. Genetic interaction analysis suggested the involvement of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the control of GO toxicity on longevity. Moreover, intestinal RNA interference (RNAi) analysis demonstrated that GO reduced longevity by affecting the functions of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the intestine. DAF-16 could also regulate GO toxicity on longevity by functioning upstream of SOD-3, which encodes an antioxidation system that prevents the accumulation of oxidative stress. Therefore, intestinal insulin signaling may encode two different molecular mechanisms responsible for the GO toxicity in inducing the shortened longevity. Our results highlight the key role of insulin signaling pathway in the control of GO toxicity in organisms.

Lifelong pathways to longevity: personality, relationships, flourishing, and health.

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Kern, Margaret L; Della Porta, Serenity S; Friedman, Howard S

2014-12-01

Building upon decades of research with the lifelong (nine-decade) Terman Life Cycle Study, we present a life pathway model for understanding human thriving that accounts for long-term individual difference in health and longevity, with a particular focus on child personality and adult social relationships. Developing data derived and supplemented from the Terman study (N = 570 males, 451 females), we employed regression and survival analyses to test models of childhood personality predicting adult psychosocial factors (subjective well-being, family relationships, community involvement, subjective achievement, hardships) and subsequent longevity. Child personality differentially related to midlife social relationships, well-being, and hardships. Conscientiousness and good social relationships predicted longer life, whereas subjective well-being was unrelated to mortality risk. Examining multiple life factors across long time periods uncovers important pathways through which personality relates to premature mortality or longevity. Typical stress-and-illness models are untenable and should be replaced with life span trajectory approaches. © 2013 Wiley Periodicals, Inc.

Transcriptional regulation of Caenorhabditis elegans FOXO/DAF-16 modulates lifespan.

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Bansal, Ankita; Kwon, Eun-Soo; Conte, Darryl; Liu, Haibo; Gilchrist, Michael J; MacNeil, Lesley T; Tissenbaum, Heidi A

2014-01-01

Insulin/IGF-1 signaling plays a central role in longevity across phylogeny. In C. elegans, the forkhead box O (FOXO) transcription factor, DAF-16, is the primary target of insulin/IGF-1 signaling, and multiple isoforms of DAF-16 (a, b, and d/f) modulate lifespan, metabolism, dauer formation, and stress resistance. Thus far, across phylogeny modulation of mammalian FOXOs and DAF-16 have focused on post-translational regulation with little focus on transcriptional regulation. In C. elegans, we have previously shown that DAF-16d/f cooperates with DAF-16a to promote longevity. In this study, we generated transgenic strains expressing near-endogenous levels of either daf-16a or daf-16d/f, and examined temporal expression of the isoforms to further define how these isoforms contribute to lifespan regulation. Here, we show that DAF-16a is sensitive both to changes in gene dosage and to alterations in the level of insulin/IGF-1 signaling. Interestingly, we find that as worms age, the intestinal expression of daf-16d/f but not daf-16a is dramatically upregulated at the level of transcription. Preventing this transcriptional upregulation shortens lifespan, indicating that transcriptional regulation of daf-16d/f promotes longevity. In an RNAi screen of transcriptional regulators, we identify elt-2 (GATA transcription factor) and swsn-1 (core subunit of SWI/SNF complex) as key modulators of daf-16d/f gene expression. ELT-2 and another GATA factor, ELT-4, promote longevity via both DAF-16a and DAF-16d/f while the components of SWI/SNF complex promote longevity specifically via DAF-16d/f. Our findings indicate that transcriptional control of C. elegans FOXO/daf-16 is an essential regulatory event. Considering the conservation of FOXO across species, our findings identify a new layer of FOXO regulation as a potential determinant of mammalian longevity and age-related diseases such as cancer and diabetes.

Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes.

Science.gov (United States)

Goldberg, Alexander A; Richard, Vincent R; Kyryakov, Pavlo; Bourque, Simon D; Beach, Adam; Burstein, Michelle T; Glebov, Anastasia; Koupaki, Olivia; Boukh-Viner, Tatiana; Gregg, Christopher; Juneau, Mylène; English, Ann M; Thomas, David Y; Titorenko, Vladimir I

2010-07-01

In chronologically aging yeast, longevity can be extended by administering a caloric restriction (CR) diet or some small molecules. These life-extending interventions target the adaptable target of rapamycin (TOR) and cAMP/protein kinase A (cAMP/PKA) signaling pathways that are under the stringent control of calorie availability. We designed a chemical genetic screen for small molecules that increase the chronological life span of yeast under CR by targeting lipid metabolism and modulating housekeeping longevity pathways that regulate longevity irrespective of the number of available calories. Our screen identifies lithocholic acid (LCA) as one of such molecules. We reveal two mechanisms underlying the life-extending effect of LCA in chronologically aging yeast. One mechanism operates in a calorie availability-independent fashion and involves the LCA-governed modulation of housekeeping longevity assurance pathways that do not overlap with the adaptable TOR and cAMP/PKA pathways. The other mechanism extends yeast longevity under non-CR conditions and consists in LCA-driven unmasking of the previously unknown anti-aging potential of PKA. We provide evidence that LCA modulates housekeeping longevity assurance pathways by suppressing lipid-induced necrosis, attenuating mitochondrial fragmentation, altering oxidation-reduction processes in mitochondria, enhancing resistance to oxidative and thermal stresses, suppressing mitochondria-controlled apoptosis, and enhancing stability of nuclear and mitochondrial DNA.

pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity.

Science.gov (United States)

Deprez, Marie-Anne; Eskes, Elja; Wilms, Tobias; Ludovico, Paula; Winderickx, Joris

2018-01-12

The plasma membrane H + -ATPase Pma1 and the vacuolar V-ATPase act in close harmony to tightly control pH homeostasis, which is essential for a vast number of physiological processes. As these main two regulators of pH are responsive to the nutritional status of the cell, it seems evident that pH homeostasis acts in conjunction with nutrient-induced signalling pathways. Indeed, both PKA and the TORC1-Sch9 axis influence the proton pumping activity of the V-ATPase and possibly also of Pma1. In addition, it recently became clear that the proton acts as a second messenger to signal glucose availability via the V-ATPase to PKA and TORC1-Sch9. Given the prominent role of nutrient signalling in longevity, it is not surprising that pH homeostasis has been linked to ageing and longevity as well. A first indication is provided by acetic acid, whose uptake by the cell induces toxicity and affects longevity. Secondly, vacuolar acidity has been linked to autophagic processes, including mitophagy. In agreement with this, a decline in vacuolar acidity was shown to induce mitochondrial dysfunction and shorten lifespan. In addition, the asymmetric inheritance of Pma1 has been associated with replicative ageing and this again links to repercussions on vacuolar pH. Taken together, accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.

The Statistics of Health and Longevity

DEFF Research Database (Denmark)

Zarulli, Virginia

Increases in human longevity have made it critical to distinguish healthy longevity from longevity without regard to health. We present a new method for calculating the statistics of healthy longevity which extends, in several directions, current calculations of health expectancy (HE) and disabil......Increases in human longevity have made it critical to distinguish healthy longevity from longevity without regard to health. We present a new method for calculating the statistics of healthy longevity which extends, in several directions, current calculations of health expectancy (HE......) and disability-adjusted life years (DALYs), from data on prevalence of health conditions. Current methods focus on binary conditions (e.g., disabled or not disabled) or on categorical classifications (e.g. in good, poor, or very bad health) and report only expectations. Our method, based on Markov chain theory...

MicroRNA mir-34 provides robustness to environmental stress response via the DAF-16 network in C. elegans

NARCIS (Netherlands)

Isik, Meltem; Blackwell, T. Keith; Berezikov, Eugene

2016-01-01

Diverse stresses and aging alter expression levels of microRNAs, suggesting a role for these posttranscriptional regulators of gene expression in stress modulation and longevity. Earlier studies demonstrated a central role for the miR-34 family in promoting cell cycle arrest and cell death following

Delayed and accelerated aging share common longevity assurance mechanisms

NARCIS (Netherlands)

Schumacher, B.; van der Pluijm, I.; Moorhouse, M.J.; Kosteas, T.; Robinson, A.R.; Suh, Y.; Breit, T.M.; van Steeg, H.; Niedernhofer, L.J.; van IJcken, W.; Bartke, A.; Spindler, S.R.; Hoeijmakers, J.H.J.; van der Horst, G.T.J.; Garinis, G.A.

2008-01-01

Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the

Delayed and accelerated aging share common longevity assurance mechanisms

NARCIS (Netherlands)

B. Schumacher (Björn); I. van der Pluijm (Ingrid); M.J. Moorhouse (Michael); T. Kosteas (Theodore); A.R. Robinson (Andria Rasile); Y. Suh (Yousin); T.M. Breit (Timo); H. van Steeg (Harry); L.J. Niedernhofer (Laura); W.F.J. van IJcken (Wilfred); A. Bartke (Andrzej); S.R. Spindler (Stephen); J.H.J. Hoeijmakers (Jan); G.T.J. van der Horst (Gijsbertus); G.A. Garinis (George)

2008-01-01

textabstractMutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between

Forever Young: Mechanisms of Natural Anoxia Tolerance and Potential Links to Longevity

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Anastasia Krivoruchko

2010-01-01

Full Text Available While mammals cannot survive oxygen deprivation for more than a few minutes without sustaining severe organ damage, some animals have mastered anaerobic life. Freshwater turtles belonging to the Trachemys and Chrysemys genera are the champion facultative anaerobes of the vertebrate world, often surviving without oxygen for many weeks at a time. The physiological and biochemical mechanisms that underlie anoxia tolerance in turtles include profound metabolic rate depression, post-translational modification of proteins, strong antioxidant defenses, activation of specific stress-responsive transcription factors, and enhanced expression of cyto-protective proteins. Turtles are also known for their incredible longevity and display characteristics of “negligible senescence.” We propose that the robust stress-tolerance mechanisms that permit long term anaerobiosis by turtles may also support the longevity of these animals. Many of the mechanisms involved in natural anoxia tolerance, such as hypometabolism or the induction of various protective proteins/pathways, have been shown to play important roles in mammalian oxygen-related diseases and improved understanding of how cells survive without oxygen could aid in the understanding and treatment of various pathological conditions that involve hypoxia or oxidative stress. In the present review we discuss the recent advances made in understanding the molecular nature of anoxia tolerance in turtles and the potential links between this tolerance and longevity.

Forever young: Mechanisms of natural anoxia tolerance and potential links to longevity

Science.gov (United States)

Krivoruchko, Anastasia

2010-01-01

While mammals cannot survive oxygen deprivation for more than a few minutes without sustaining severe organ damage, some animals have mastered anaerobic life. Freshwater turtles belonging to the Trachemys and Chrysemys genera are the champion facultative anaerobes of the vertebrate world, often surviving without oxygen for many weeks at a time. The physiological and biochemical mechanisms that underlie anoxia tolerance in turtles include profound metabolic rate depression, post-translational modification of proteins, strong antioxidant defenses, activation of specific stress-responsive transcription factors, and enhanced expression of cyto-protective proteins. Turtles are also known for their incredible longevity and display characteristics of “negligible senescence.” We propose that the robust stress-tolerance mechanisms that permit long term anaerobiosis by turtles may also support the longevity of these animals. Many of the mechanisms involved in natural anoxia tolerance, such as hypometabolism or the induction of various protective proteins/pathways, have been shown to play important roles in mammalian oxygen-related diseases and improved understanding of how cells survive without oxygen could aid in the understanding and treatment of various pathological conditions that involve hypoxia or oxidative stress. In the present review we discuss the recent advances made in understanding the molecular nature of anoxia tolerance in turtles and the potential links between this tolerance and longevity. PMID:20716943

New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen.

Directory of Open Access Journals (Sweden)

Malene Hansen

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.

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.

pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity

Directory of Open Access Journals (Sweden)

Marie-Anne Deprez

2018-01-01

Full Text Available The plasma membrane H+-ATPase Pma1 and the vacuolar V-ATPase act in close harmony to tightly control pH homeostasis, which is essential for a vast number of physiological processes. As these main two regulators of pH are responsive to the nutritional status of the cell, it seems evident that pH homeostasis acts in conjunction with nutrient-induced signalling pathways. Indeed, both PKA and the TORC1-Sch9 axis influence the proton pumping activity of the V-ATPase and possibly also of Pma1. In addition, it recently became clear that the proton acts as a second messenger to signal glucose availability via the V-ATPase to PKA and TORC1-Sch9. Given the prominent role of nutrient signalling in longevity, it is not surprising that pH homeostasis has been linked to ageing and longevity as well. A first indication is provided by acetic acid, whose uptake by the cell induces toxicity and affects longevity. Secondly, vacuolar acidity has been linked to autophagic processes, including mitophagy. In agreement with this, a decline in vacuolar acidity was shown to induce mitochondrial dysfunction and shorten lifespan. In addition, the asymmetric inheritance of Pma1 has been associated with replicative ageing and this again links to repercussions on vacuolar pH. Taken together, accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.

Nitrogen and carbon source balance determines longevity, independently of fermentative or respiratory metabolism in the yeast Saccharomyces cerevisiae.

Science.gov (United States)

Santos, Júlia; Leitão-Correia, Fernanda; Sousa, Maria João; Leão, Cecília

2016-04-26

Dietary regimens have proven to delay aging and age-associated diseases in several eukaryotic model organisms but the input of nutritional balance to longevity regulation is still poorly understood. Here, we present data on the role of single carbon and nitrogen sources and their interplay in yeast longevity. Data demonstrate that ammonium, a rich nitrogen source, decreases chronological life span (CLS) of the prototrophic Saccharomyces cerevisiae strain PYCC 4072 in a concentration-dependent manner and, accordingly, that CLS can be extended through ammonium restriction, even in conditions of initial glucose abundance. We further show that CLS extension depends on initial ammonium and glucose concentrations in the growth medium, as long as other nutrients are not limiting. Glutamine, another rich nitrogen source, induced CLS shortening similarly to ammonium, but this effect was not observed with the poor nitrogen source urea. Ammonium decreased yeast CLS independently of the metabolic process activated during aging, either respiration or fermentation, and induced replication stress inhibiting a proper cell cycle arrest in G0/G1 phase. The present results shade new light on the nutritional equilibrium as a key factor on cell longevity and may contribute for the definition of interventions to promote life span and healthy aging.

Regulation of longevity and oxidative stress by nutritional interventions: role of methionine restriction.

Science.gov (United States)

Sanchez-Roman, Ines; Barja, Gustavo

2013-10-01

Comparative studies indicate that long-lived mammals have low rates of mitochondrial reactive oxygen species production (mtROSp) and oxidative damage in their mitochondrial DNA (mtDNA). Dietary restriction (DR), around 40%, extends the mean and maximum life span of a wide range of species and lowers mtROSp and oxidative damage to mtDNA, which supports the mitochondrial free radical theory of aging (MFRTA). Regarding the dietary factor responsible for the life extension effect of DR, neither carbohydrate nor lipid restriction seems to modify maximum longevity. However protein restriction (PR) and methionine restriction (at least 80% MetR) increase maximum lifespan in rats and mice. Interestingly, only 7weeks of 40% PR (at least in liver) or 40% MetR (in all the studied organs, heart, brain, liver or kidney) is enough to decrease mtROSp and oxidative damage to mtDNA in rats, whereas neither carbohydrate nor lipid restriction changes these parameters. In addition, old rats also conserve the capacity to respond to 7weeks of 40% MetR with these beneficial changes. Most importantly, 40% MetR, differing from what happens during both 40% DR and 80% MetR, does not decrease growth rate and body size of rats. All the available studies suggest that the decrease in methionine ingestion that occurs during DR is responsible for part of the aging-delaying effect of this intervention likely through the decrease of mtROSp and ensuing DNA damage that it exerts. We conclude that lowering mtROS generation is a conserved mechanism, shared by long-lived species and dietary, protein, and methionine restricted animals, that decreases damage to macromolecules situated near the complex I mtROS generator, especially mtDNA. This would decrease the accumulation rate of somatic mutations in mtDNA and maybe finally also in nuclear DNA. Copyright © 2013 Elsevier Inc. All rights reserved.

Longevity Genes Revealed by Integrative Analysis of Isoform-Specific daf-16/FoxO Mutants of Caenorhabditis elegans.

Science.gov (United States)

Chen, Albert Tzong-Yang; Guo, Chunfang; Itani, Omar A; Budaitis, Breane G; Williams, Travis W; Hopkins, Christopher E; McEachin, Richard C; Pande, Manjusha; Grant, Ana R; Yoshina, Sawako; Mitani, Shohei; Hu, Patrick J

2015-10-01

FoxO transcription factors promote longevity across taxa. How they do so is poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms of the FoxO transcription factor DAF-16 extend life span in the context of reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed an integrative analysis of isoform-specific daf-16/FoxO mutants. In contrast to previous studies suggesting that DAF-16F plays a more prominent role in life span control than DAF-16A, isoform-specific daf-16/FoxO mutant phenotypes and whole transcriptome profiling revealed a predominant role for DAF-16A over DAF-16F in life span control, stress resistance, and target gene regulation. Integration of these datasets enabled the prioritization of a subset of 92 DAF-16/FoxO target genes for functional interrogation. Among 29 genes tested, two DAF-16A-specific target genes significantly influenced longevity. A loss-of-function mutation in the conserved gene gst-20, which is induced by DAF-16A, reduced life span extension in the context of daf-2/IGFR RNAi without influencing longevity in animals subjected to control RNAi. Therefore, gst-20 promotes DAF-16/FoxO-dependent longevity. Conversely, a loss-of-function mutation in srr-4, a gene encoding a seven-transmembrane-domain receptor family member that is repressed by DAF-16A, extended life span in control animals, indicating that DAF-16/FoxO may extend life span at least in part by reducing srr-4 expression. Our discovery of new longevity genes underscores the efficacy of our integrative strategy while providing a general framework for identifying specific downstream gene regulatory events that contribute substantially to transcription factor functions. As FoxO transcription factors have conserved functions in promoting longevity and may be dysregulated in aging-related diseases, these findings promise to illuminate fundamental

Oxidative stress, neuroendocrine function and behavior in an animal model of extended longevity

NARCIS (Netherlands)

Berry, Alessandra

2010-01-01

Stress and oxidative stress (OS) might act synergistically to exacerbate the neuronal decay associated with aging. Recent evidence has shown a redox regulation of the function of the glucocorticoid receptors as nuclear transcription factors. The lack of the p66Shc gene reduces OS and increases

Drosophila Longevity Assurance Conferred by Reduced Insulin Receptor Substrate Chico Partially Requires d4eBP.

Directory of Open Access Journals (Sweden)

Hua Bai

Full Text Available Mutations of the insulin/IGF signaling (IIS pathway extend Drosophila lifespan. Based on genetic epistasis analyses, this longevity assurance is attributed to downstream effects of the FOXO transcription factor. However, as reported FOXO accounts for only a portion of the observed longevity benefit, suggesting there are additional outputs of IIS to mediate aging. One candidate is target of rapamycin complex 1 (TORC1. Reduced TORC1 activity is reported to slow aging, whereas reduced IIS is reported to repress TORC1 activity. The eukaryotic translation initiation factor 4E binding protein (4E-BP is repressed by TORC1, and activated 4E-BP is reported to increase Drosophila lifespan. Here we use genetic epistasis analyses to test whether longevity assurance mutants of chico, the Drosophila insulin receptor substrate homolog, require Drosophila d4eBP to slow aging. In chico heterozygotes, which are robustly long-lived, d4eBP is required but not sufficient to slow aging. Remarkably, d4eBP is not required or sufficient for chico homozygotes to extend longevity. Likewise, chico heterozygote females partially require d4eBP to preserve age-dependent locomotion, and both chico genotypes require d4eBP to improve stress-resistance. Reproduction and most measures of growth affected by either chico genotype are always independent of d4eBP. In females, chico heterozygotes paradoxically produce more rather than less phosphorylated 4E-BP (p4E-BP. Altered IRS function within the IIS pathway of Drosophila appears to have partial, conditional capacity to regulate aging through an unconventional interaction with 4E-BP.

A family longevity selection score: ranking sibships by their longevity, size, and availability for study.

Science.gov (United States)

Sebastiani, Paola; Hadley, Evan C; Province, Michael; Christensen, Kaare; Rossi, Winifred; Perls, Thomas T; Ash, Arlene S

2009-12-15

Family studies of exceptional longevity can potentially identify genetic and other factors contributing to long life and healthy aging. Although such studies seek families that are exceptionally long lived, they also need living members who can provide DNA and phenotype information. On the basis of these considerations, the authors developed a metric to rank families for selection into a family study of longevity. Their measure, the family longevity selection score (FLoSS), is the sum of 2 components: 1) an estimated family longevity score built from birth-, gender-, and nation-specific cohort survival probabilities and 2) a bonus for older living siblings. The authors examined properties of FLoSS-based family rankings by using data from 3 ongoing studies: the New England Centenarian Study, the Framingham Heart Study, and screenees for the Long Life Family Study. FLoSS-based selection yields families with exceptional longevity, satisfactory sibship sizes and numbers of living siblings, and high ages. Parameters in the FLoSS formula can be tailored for studies of specific populations or age ranges or with different conditions. The first component of the FLoSS also provides a conceptually sound survival measure to characterize exceptional longevity in individuals or families in various types of studies and correlates well with later-observed longevity.

Laboratory selection for increased longevity in Drosophila melanogaster reduces field performance

DEFF Research Database (Denmark)

Wit, Janneke; Kristensen, Torsten Nygaard; Sarup, Pernille

2013-01-01

, environmental temperature and longevity selection on performance in the fieldwas tested. Flies fromlongevity selected and control lines of different ages (2, 5, 10 and 15 days) were released in an environment free of natural food sources. Control flies were tested at low, intermediate and high temperatures......Drosophilamelanogaster is frequently used in ageing studies to elucidate whichmechanisms determine the onset and progress of senescence. Lines selected for increased longevity have often been shown to performaswell as or superior to control lines in life history, stress resistance and behavioural......,while longevity selected flieswere tested at the intermediate temperature only. The ability of flies to locate and reach a food sourcewas tested. Flies of intermediate agewere generally better at locating resources than both younger and older flies, where hot and cold environments accelerate the senescent decline...

"Predicting" parental longevity from offspring endophenotypes

DEFF Research Database (Denmark)

Yashin, Anatoli I; Arbeev, Konstantin G; Kulminski, Alexander

2010-01-01

for exceptional survival. These endophenotypes could be studied in families to identify human longevity genes and elucidate possible mechanisms of their influence on longevity. In this paper, we analyze data collected in the Long Life Family Study (LLFS) investigating whether indicators of physiological state......While there is evidence that longevity runs in families, the study of long-lived families is complicated by the fact that longevity-related information is available only for the oldest old, many of whom may be deceased and unavailable for testing, and information on other living family members......, primarily descendents, is censored. This situation requires a creative approach for analyzing determinants of longevity in families. There are likely biomarkers that predict an individual's longevity, suggesting the possibility that those biomarkers which are heritable may constitute valuable endophenotypes...

Telomeres, Nutrition, and Longevity: Can We Really Navigate Our Aging?

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Vidacek, Nikolina Škrobot; Nanic, Lucia; Ravlic, Sanda; Sopta, Mary; Geric, Marko; Gajski, Goran; Garaj-Vrhovac, Vera; Rubelj, Ivica

2017-12-12

Telomeres are dynamic chromosome-end structures that serve as guardians of genome stability. They are known to be one of the major determinants of aging and longevity in higher mammals. Studies have demonstrated a direct correlation between telomere length and life expectancy, stress, DNA damage, and onset of aging-related diseases. This review discusses the most important factors that influence our telomeres. Various genetic and environmental factors such as diet, physical activity, obesity, and stress are known to influence health and longevity as well as telomere dynamics. Individuals currently have the opportunity to modulate the dynamics of their aging and health span, monitor these processes, and even make future projections by following their telomere dynamics. As telomeres react to positive as well as negative health factors, we should be able to directly influence our telomere metabolism, slow their deterioration, and diminish our aging and perhaps extend our life and health span. © The Author(s) 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.

Predictors of Exceptional Longevity: Effects of Early-Life and Midlife Conditions, and Familial Longevity.

Science.gov (United States)

Gavrilov, Leonid A; Gavrilova, Natalia S

Knowledge of strong predictors of mortality and longevity is very important for actuarial science and practice. Earlier studies found that parental characteristics as well as early-life conditions and midlife environment play a significant role in survival to advanced ages. However, little is known about the simultaneous effects of these three factors on longevity. This ongoing study attempts to fill this gap by comparing centenarians born in the United States in 1890-1891 with peers born in the same years who died at age 65. The records for centenarians and controls were taken from computerized family histories, which were then linked to 1900 and 1930 U.S. censuses. As a result of this linkage procedure, 765 records of confirmed centenarians and 783 records of controls were obtained. Analysis with multivariate logistic regression found the existence of both general and gender-specific predictors of human longevity. General predictors common for men and women are paternal and maternal longevity. Gender-specific predictors of male longevity are occupation as a farmer at age 40, Northeastern region of birth in the United States, and birth in the second half of year. A gender-specific predictor of female longevity is the availability of radio in the household according to the 1930 U.S. census. Given the importance of familial longevity as an independent predictor of survival to advanced ages, we conducted a comparative study of biological and nonbiological relatives of centenarians using a larger sample of 1,945 validated U.S. centenarians born in 1880-1895. We found that male gender of centenarian has a significant positive effect on survival of adult male relatives (brothers and fathers) but not female blood relatives. Life span of centenarian siblings-in-law is lower compared to life span of centenarian siblings and does not depend on centenarian gender. Wives of male centenarians (who share lifestyle and living conditions) have a significantly better survival

Investigation of the 5q33.3 longevity locus and age-related phenotypes

DEFF Research Database (Denmark)

Nygaard, Marianne; Thinggaard, Mikael; Christensen, Kaare

2017-01-01

A large meta-analysis recently found the 5q33.3 locus to be associated with survival to ≥ 90 years and lower all-cause mortality, thus suggesting it as a third human longevity locus alongside APOE and FOXO3A. The 5q33.3 locus has previously been associated with blood pressure regulation and cardi......A large meta-analysis recently found the 5q33.3 locus to be associated with survival to ≥ 90 years and lower all-cause mortality, thus suggesting it as a third human longevity locus alongside APOE and FOXO3A. The 5q33.3 locus has previously been associated with blood pressure regulation...... and cardiovascular diseases in middle-aged individuals. However, part of the influence on mortality appears to be independent of cardiovascular phenotypes, and the role of the 5q33.3 locus in longevity and survival is therefore still partly unknown. We investigated the association between the longevity......-associated variant rs2149954 on chromosome 5q33.3 and age-related phenotypes in two cohorts of 1,588 and 1,271 long-lived individuals (mean ages 93.1 and 95.9 years, respectively) as well as in 700 middle-aged and 677 elderly individuals (mean ages 52.5 and 78.7 years). Altogether, nominally significant associations...

Replication studies in longevity

DEFF Research Database (Denmark)

Varcasia, O; Garasto, S; Rizza, T

2001-01-01

In Danes we replicated the 3'APOB-VNTR gene/longevity association study previously carried out in Italians, by which the Small alleles (less than 35 repeats) had been identified as frailty alleles for longevity. In Danes, neither genotype nor allele frequencies differed between centenarians and 20...

Comparative study of physico-chemical parameters of drinking water from some longevity and non-longevity areas of China.

Science.gov (United States)

Du, Yajun; Luo, Kunli; Hussain, Rahib

2017-06-01

There is an obvious regional longevity phenomenon in China and many longevity counties are located in South China. This study was carried out to find the characteristics of elemental contents of drinking water in longevity areas in South China and the differences to non-longevity areas in China. A total of 128 drinking water samples were collected from longevity areas in South China (n = 40), non-longevity areas in South China (n = 74) and non-longevity areas in North China (n = 14) and 46 parameters of water were determined or calculated. The results showed that drinking water in longevity areas of South China had a high ratio of sum concentration of essential micro-elements in sum concentration of micro-elements (SCME) and a low ratio of sum concentration of hazardous micro-elements in SCME. The concentration of total hardness (TH) and strontium in drinking water was 157.82 mg/L and 82.1 μg/L, respectively, and they were 14.61 mg/L, 7.45 μg/L and 291.69 mg/L, 748.65 μg/L in the non-longevity areas of South and North China, respectively. The study concluded that drinking water containing 157.82 mg/L TH and 82.1 μg/L strontium in South China may be optimum to human health.

Longevity extension of worker honey bees (Apis mellifera by royal jelly: optimal dose and active ingredient

Directory of Open Access Journals (Sweden)

Wenchao Yang

2017-03-01

Full Text Available In the Western honey bee, Apis mellifera, queens and workers have different longevity although they share the same genome. Queens consume royal jelly (RJ as the main food throughout their life, including as adults, but workers only eat worker jelly when they are larvae less than 3 days old. In order to explore the effect of RJ and the components affecting longevity of worker honey bees, we first determined the optimal dose for prolonging longevity of workers as 4% RJ in 50% sucrose solution, and developed a method of obtaining long lived workers. We then compared the effects of longevity extension by RJ 4% with bee-collected pollen from rapeseed (Brassica napus. Lastly, we determined that a water soluble RJ protein obtained by precipitation with 60% ammonium sulfate (RJP60 contained the main component for longevity extension after comparing the effects of RJ crude protein extract (RJCP, RJP30 (obtained by precipitation with 30% ammonium sulfate, and RJ ethanol extract (RJEE. Understanding what regulates worker longevity has potential to help increase colony productivity and improve crop pollination efficiency.

Longevity extension of worker honey bees (Apis mellifera) by royal jelly: optimal dose and active ingredient.

Science.gov (United States)

Yang, Wenchao; Tian, Yuanyuan; Han, Mingfeng; Miao, Xiaoqing

2017-01-01

In the Western honey bee, Apis mellifera , queens and workers have different longevity although they share the same genome. Queens consume royal jelly (RJ) as the main food throughout their life, including as adults, but workers only eat worker jelly when they are larvae less than 3 days old. In order to explore the effect of RJ and the components affecting longevity of worker honey bees, we first determined the optimal dose for prolonging longevity of workers as 4% RJ in 50% sucrose solution, and developed a method of obtaining long lived workers. We then compared the effects of longevity extension by RJ 4% with bee-collected pollen from rapeseed ( Brassica napus ). Lastly, we determined that a water soluble RJ protein obtained by precipitation with 60% ammonium sulfate (RJP 60 ) contained the main component for longevity extension after comparing the effects of RJ crude protein extract (RJCP), RJP 30 (obtained by precipitation with 30% ammonium sulfate), and RJ ethanol extract (RJEE). Understanding what regulates worker longevity has potential to help increase colony productivity and improve crop pollination efficiency.

Deleting the 14-3-3 protein Bmh1 extends life span in Saccharomyces cerevisiae by increasing stress response.

Science.gov (United States)

Wang, Chen; Skinner, Craig; Easlon, Erin; Lin, Su-Ju

2009-12-01

Enhanced stress response has been suggested to promote longevity in many species. Calorie restriction (CR) and conserved nutrient-sensing target of rapamycin (TOR) and protein kinase A (PKA) pathways have also been suggested to extend life span by increasing stress response, which protects cells from age-dependent accumulation of oxidative damages. Here we show that deleting the yeast 14-3-3 protein, Bmh1, extends chronological life span (CLS) by activating the stress response. 14-3-3 proteins are highly conserved chaperone-like proteins that play important roles in many cellular processes. bmh1Delta-induced heat resistance and CLS extension require the general stress-response transcription factors Msn2, Msn4, and Rim15. The bmh1Delta mutant also displays a decreased reactive oxygen species level and increased heat-shock-element-driven transcription activity. We also show that BMH1 genetically interacts with CR and conserved nutrient-sensing TOR- and PKA-signaling pathways to regulate life span. Interestingly, the level of phosphorylated Ser238 on Bmh1 increases during chronological aging, which is delayed by CR or by reduced TOR activities. In addition, we demonstrate that PKA can directly phosphorylate Ser238 on Bmh1. The status of Bmh1 phosphorylation is therefore likely to play important roles in life-span regulation. Together, our studies suggest that phosphorylated Bmh1 may cause inhibitory effects on downstream longevity factors, including stress-response proteins. Deleting Bmh1 may eliminate the inhibitory effects of Bmh1 on these longevity factors and therefore extends life span.

Induction of autophagy by spermidine promotes longevity.

Science.gov (United States)

Eisenberg, Tobias; Knauer, Heide; Schauer, Alexandra; Büttner, Sabrina; Ruckenstuhl, Christoph; Carmona-Gutierrez, Didac; Ring, Julia; Schroeder, Sabrina; Magnes, Christoph; Antonacci, Lucia; Fussi, Heike; Deszcz, Luiza; Hartl, Regina; Schraml, Elisabeth; Criollo, Alfredo; Megalou, Evgenia; Weiskopf, Daniela; Laun, Peter; Heeren, Gino; Breitenbach, Michael; Grubeck-Loebenstein, Beatrix; Herker, Eva; Fahrenkrog, Birthe; Fröhlich, Kai-Uwe; Sinner, Frank; Tavernarakis, Nektarios; Minois, Nadege; Kroemer, Guido; Madeo, Frank

2009-11-01

Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice. In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan. The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.

28 CFR 345.55 - Longevity pay.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Longevity pay. 345.55 Section 345.55... (FPI) INMATE WORK PROGRAMS Inmate Pay and Benefits § 345.55 Longevity pay. (a) Except as provided in paragraph (b) of this section, an inmate earns longevity pay raises after 18 months spent in FPI work status...

Hormetic efficacy of rutin to promote longevity in Drosophila melanogaster.

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Chattopadhyay, Debarati; Chitnis, Atith; Talekar, Aishwarya; Mulay, Prajakta; Makkar, Manyata; James, Joel; Thirumurugan, Kavitha

2017-06-01

Hormetins are compounds that mediate hormesis by being beneficial at low doses but detrimental at high doses. Recent studies have highlighted that many compounds that extended lifespan in model organisms did so by mediating hormesis. Rutin is a glycosylate conjugate of quercetin and rutinose and is abundant in citrus fruits and buckwheat seeds. Rutin possess ROS scavenging, anti-cancer, cardio-protective, skin-regenerative and neuro-protective properties. Drosophila melanogaster is an attractive model organism for longevity studies owing to its homology of organ and cellular-pathways with mammals. In this study, we aimed to understand the effect of rutin on extending longevity in Drosophila melanogaster. Male and female flies were administered with a range of rutin doses (100-800 µM) to analyse whether rutin mediated lifespan-extension by hormesis. Effect of rutin on physiological parameters like food intake, fecundity, climbing activity, development and resistance to various stresses was also studied. Lifespan assays showed that rutin at 200 and 400 µM significantly extended median lifespan in both male and female flies beyond which flies exhibited drastically reduced longevity. Increase in survival at 400 µM was associated with reduced food intake and fecundity. Flies exhibited improved climbing capability with both 200 and 400 µM rutin. Flies fed with 100 and 200 µM rutin exhibited enhanced survival upon exposure to oxidative stress with 400 µM rutin exhibiting no improvement in median lifespan following oxidative stress. Analysis of endogenous peroxide upon treatment with rutin (100-400 µM) with or without 5% H 2 O 2 showed elevated levels of endogenous peroxide with 400 µM rutin whereas no increase in hydrogen peroxide level was observed with rutin at 100 and 200 µM. Finally, gene expression studies in male flies revealed that rutin treatment at 200 and/or 400 µM elevated transcript levels of dFoxO, MnSod, Cat, dTsc1, dTsc2, Thor, dAtg1, d

Environmental control and control of the environment: the basis of longevity in bivalves.

Science.gov (United States)

Abele, Doris; Philipp, Eva

2013-01-01

Longevity and ageing are two sides of a coin, leaving the question open as to which one is the cause and which one the effect. At the individual level, the physiological rate of ageing determines the length of life (= individual longevity, as long as death results from old age and not from disease or other impacts). Individual longevity depends on the direct influence of environmental conditions with respect to nutrition, and the possibility for and timing of reproduction, as well as on the energetic costs animals invest in behavioural and physiological stress defence. All these environmental effectors influence hormonal and cellular signalling pathways that modify the individual physiological condition, the reproductive strategy, and the rate of ageing. At the species level, longevity (= maximum lifespan) is the result of an evolutionary process and, thus, largely determined by the species' behavioural and physiological adaptations to its ecological niche. Specifically, reproductive and breeding strategies have to be optimized in relation to local environmental conditions in different habitats. As a result of adaptive and evolutionary processes, species longevity is genetically underpinned, not necessarily by a few ageing genes, but by an evolutionary process that has hierarchically shaped and optimized species genomes to function in a specific niche or environmental system. Importantly, investigations and reviews attempting to unravel the mechanistic basis of the ageing process need to differentiate clearly between the evolutionary process shaping longevity at the species level and the regulatory mechanisms that alter the individual rate of ageing. Copyright © 2012 S. Karger AG, Basel.

Longevity studies in GenomEUtwin

DEFF Research Database (Denmark)

Skytthe, Axel; Pedersen, Nancy L; Kaprio, Jaakko

2003-01-01

Previous twin studies have indicated that approximately 25% of the variation in life span can be attributed to genetic factors and recent studies have also suggested a moderate clustering of extreme longevity within families. Here we discuss various definitions of extreme longevity and some...... analytical approaches with special attention to the challenges due to censored data. Lexis diagrams are provided for the Danish, Dutch, Finnish, Italian, Norwegian, and Swedish Twin registries hereby outlining possibilities for longevity studies within GenomEUtwin. We extend previous analyses of lifespan...

Reconstructing a Network of Stress-Response Regulators via Dynamic System Modeling of Gene Regulation

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Wei-Sheng Wu

2008-01-01

Full Text Available Unicellular organisms such as yeasts have evolved mechanisms to respond to environmental stresses by rapidly reorganizing the gene expression program. Although many stress-response genes in yeast have been discovered by DNA microarrays, the stress-response transcription factors (TFs that regulate these stress-response genes remain to be investigated. In this study, we use a dynamic system model of gene regulation to describe the mechanism of how TFs may control a gene’s expression. Then, based on the dynamic system model, we develop the Stress Regulator Identification Algorithm (SRIA to identify stress-response TFs for six kinds of stresses. We identified some general stress-response TFs that respond to various stresses and some specific stress-response TFs that respond to one specifi c stress. The biological significance of our findings is validated by the literature. We found that a small number of TFs is probably suffi cient to control a wide variety of expression patterns in yeast under different stresses. Two implications can be inferred from this observation. First, the response mechanisms to different stresses may have a bow-tie structure. Second, there may be regulatory cross-talks among different stress responses. In conclusion, this study proposes a network of stress-response regulators and the details of their actions.

77 FR 60948 - Stress Testing of Regulated Entities

Science.gov (United States)

2012-10-05

... regulated by a primary federal financial regulatory agency, to conduct annual stress tests to determine... the regulated entities under the Federal Housing Enterprises Financial Safety and Soundness Act of... regulated by a primary Federal financial regulatory agency shall conduct annual stress tests * * * (emphasis...

Longevity of HDPE Geomembranes in Geoenvironmental Applications

Science.gov (United States)

Ewais, Amr Mohamed Ragab Abdel Samad

With sufficient time, a high density polyethylene geomembrane will degrade and lose its engineering properties until ruptures signal the end of its service-life. This thesis examines the longevity of nine different geomembranes; five of them were of different thickness manufactured from the same resin. The degradation of properties and time to failure are investigated for geomembranes: in immersion tests; as a part of a landfill composite liner; and, exposed to the elements. The different thermal and stress histories associated with manufacturing geomembranes of different thickness are shown to affect their morphological structure; consequently, their stress crack resistance. When immersed in synthetic leachate, it was found that: (a) thicker geomembranes have a longer antioxidants depletion time but the effect of thickness decreases with temperature and is less than expected; (b) inferences of geomembrane's longevity based on its initial properties may be misleading because a geomembrane may chemically degrade (as manifested by the change in melt index) despite the presence of a significant amount of stabilizers (as manifested by the measured high pressure oxidative induction time); and, (c) stress crack resistance may change before antioxidant depletion or chemical degradation takes place, likely, due to changes in geomembrane morphological structure with the maximum decrease being observed at 55°C. Reductions also were measured for geomembrane immersed in air and water at 55°C. The geomembrane aged in a simulated landfill liner at 85°C is shown to have service-life as little as three years with 30,000 to >2.0 million ruptures/hectare at failure. For exposed geomembranes in Alumbrera (Argentina), samples were exhumed from two mine facilities after ~16 years of exposure. The antioxidants in exposed samples depleted to residual and the stress crack resistance had dropped to as low as 70 hours. Samples were exhumed from a different exposed geomembrane in a test

A Family Longevity Selection Score: Ranking Sibships by Their Longevity, Size, and Availability for Study

DEFF Research Database (Denmark)

Sebastiani, Paola; Hadley, Evan C; Province, Michael

2009-01-01

Family studies of exceptional longevity can potentially identify genetic and other factors contributing to long life and healthy aging. Although such studies seek families that are exceptionally long lived, they also need living members who can provide DNA and phenotype information. On the basis...... of these considerations, the authors developed a metric to rank families for selection into a family study of longevity. Their measure, the family longevity selection score (FLoSS), is the sum of 2 components: 1) an estimated family longevity score built from birth-, gender-, and nation-specific cohort survival...... probabilities and 2) a bonus for older living siblings. The authors examined properties of FLoSS-based family rankings by using data from 3 ongoing studies: the New England Centenarian Study, the Framingham Heart Study, and screenees for the Long Life Family Study. FLoSS-based selection yields families...

Emotion regulation: Exploring the impact of stress and sex

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Valerie L. Kinner

2014-11-01

Full Text Available Emotion regulation is a major prerequisite for adaptive behavior. The capacity to regulate emotions is particularly important during and after the encounter of a stressor. However the impact of acute stress and its associated neuroendocrine alterations on emotion regulation have received little attention so far. This study aimed to explore how stress-induced cortisol increases affect three different emotion regulation strategies. 72 healthy men and women were either exposed to a stressor or a control condition. Subsequently participants viewed positive and negative images and were asked to up- or down-regulate their emotional responses or simultaneously required to solve an arithmetic task (distraction. The factors stress, sex and strategy were operationalized as between group factors (n = 6 per cell. Stress caused an increase in blood pressure and higher subjective stress ratings. An increase in cortisol was observed in male participants only. In contrast to controls, stressed participants were less effective in distracting themselves from the emotional pictures. The results further suggest that in women stress enhances the ability to decrease negative emotions. These findings characterize the impact of stress and sex on emotion regulation and provide initial evidence that these factors may interact.

The homeobox protein CEH-23 mediates prolonged longevity in response to impaired mitochondrial electron transport chain in C. elegans.

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Ludivine Walter

2011-06-01

Full Text Available Recent findings indicate that perturbations of the mitochondrial electron transport chain (METC can cause extended longevity in evolutionarily diverse organisms. To uncover the molecular basis of how altered METC increases lifespan in C. elegans, we performed an RNAi screen and revealed that three predicted transcription factors are specifically required for the extended longevity of mitochondrial mutants. In particular, we demonstrated that the nuclear homeobox protein CEH-23 uniquely mediates the longevity but not the slow development, reduced brood size, or resistance to oxidative stress associated with mitochondrial mutations. Furthermore, we showed that ceh-23 expression levels are responsive to altered METC, and enforced overexpression of ceh-23 is sufficient to extend lifespan in wild-type background. Our data point to mitochondria-to-nucleus communications to be key for longevity determination and highlight CEH-23 as a novel longevity factor capable of responding to mitochondrial perturbations. These findings provide a new paradigm for how mitochondria impact aging and age-dependent diseases.

HIF-1-dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA-binding protein MAA-1

DEFF Research Database (Denmark)

Shamalnasab, Mehrnaz; Dhaoui, Manel; Thondamal, Manjunatha

2017-01-01

In yeast, the broadly conserved acyl-CoA-binding protein (ACBP) is a negative regulator of stress resistance and longevity. Here, we have turned to the nematode C. elegans as a model organism in which to determine whether ACBPs play similar roles in multicellular organisms. We systematically...... inactivated each of the seven C. elegans ACBP paralogs and found that one of them, maa-1 (which encodes membrane-associated ACBP 1), is indeed involved in the regulation of longevity. In fact, loss of maa-1 promotes lifespan extension and resistance to different types of stress. Through genetic and gene...... of the proteome. Our work extends to C. elegans the role of ACBP in aging, implicates HIF-1 in the increase of lifespan of maa-1-deficient worms, and sheds light on the anti-aging function of HIF-1. Given that both ACBP and HIF-1 are highly conserved, our results suggest the possible involvement of these proteins...

Environmentally induced transgenerational changes in seed longevity: maternal and genetic influence.

Science.gov (United States)

Mondoni, A; Orsenigo, S; Donà, M; Balestrazzi, A; Probert, R J; Hay, F R; Petraglia, A; Abeli, T

2014-06-01

Seed longevity, a fundamental plant trait for ex situ conservation and persistence in the soil of many species, varies across populations and generations that experience different climates. This study investigates the extent to which differences in seed longevity are due to genetic differences and/or modified by adaptive responses to environmental changes. Seeds of two wild populations of Silene vulgaris from alpine (wA) and lowland (wL) locations and seeds originating from their cultivation in a lowland common garden for two generations (cA1, cL1, cA2 and cL2) were exposed to controlled ageing at 45 °C, 60 % relative humidity and regularly sampled for germination and relative mRNA quantification (SvHSP17.4 and SvNRPD12). The parental plant growth environment affected the longevity of seeds with high plasticity. Seeds of wL were significantly longer lived than those of wA. However, when alpine plants were grown in the common garden, longevity doubled for the first generation of seeds produced (cA1). Conversely, longevity was similar in all lowland seed lots and did not increase in the second generation of seeds produced from alpine plants grown in the common garden (cA2). Analysis of parental effects on mRNA seed provisioning indicated that the accumulation of gene transcripts involved in tolerance to heat stress was highest in wL, cL1 and cL2, followed by cA1, cA2 and wA. Seed longevity has a genetic basis, but may show strong adaptive responses, which are associated with differential accumulation of mRNA via parental effects. Adaptive adjustments of seed longevity due to transgenerational plasticity may play a fundamental role in the survival and persistence of the species in the face of future environmental challenges. The results suggest that regeneration location may have important implications for the conservation of alpine plants held in seed banks. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All

The genetics of aging in optimal and stressful environments

International Nuclear Information System (INIS)

Parsons, P.A.

1978-01-01

The genetic basis of aging in Drosophila varies according to environment, as shown by variations in temperatures and levels of 60 Co-γ irradiation. Under conditions of extreme stress large additive differences occur not found under less acute stresses. In addition, longevities of strains are not necessarily correlated across levels of 60 C0-γ irradiation or temperatures, so that studies of the genetics of aging are not only relevant to the environment selected. Given these results on experimental animals, it appears impossible to separate clearly genetic and environmental factors determining longevity in man - a conclusion that in any case appears likely from human studies. In experimental organisms such as Drosophila, differences between genotypes for longevity are magnified under stress compared with optimal environments. Hybrid and heterozygote superiority frequently occur for density-independent physical stresses of the environment as well as density-dependent behavioral stresses due to crowding levels. It is argued that these conclusions apply to man, so that for maximum longevity genotypes are likely to be highly heterozygous. (author)

Comparison of biochemical data, blood pressure and physical activity between longevity and non-longevity districts in Japan.

Science.gov (United States)

Mori, Ichiro; Ishizuka, Tatsuo; Morita, Hiroyuki; Matsumoto, Masami; Uno, Yoshihiro; Kajita, Kazuo; Ikeda, Takahide; Fujioka, Kei; Matsubara, Kenji

2008-10-01

There is controversy about longevity-associated factors, including environmental and genetic factors. Clinical and epidemiological studies suggest that multiple risk factors decrease life-span, but there has not been a definitive report regarding the association of risk factors with longevity. The ultimate aim of the present study was to prevent the overwhelming increase in life-style-related diseases by evaluating this association in 2 districts in Japan. Plasma glucose levels, hemoglobin (Hb) A1c, lipids, dehydroepiandrosterone-sulfate, adiponectin and physical activity were examined in 133 subjects (M/F 47/86, 67+/-1 years) in Kokufu, a longevity district (mean life span: 80.4 years according to 2000 Japanese census) and 69 subjects (M/F 29/40, 62+/-1 years) in Miyama, a non-longevity district (mean life span 77.4 years, 2000 census). There were significant differences in systolic and diastolic blood pressures (BPs, p longevity, and those of HDL-C and TG, as well as glucose tolerance, might be associated with adiponectin levels.

SIRT1 ameliorates oxidative stress induced neural cell death and is down-regulated in Parkinson's disease.

Science.gov (United States)

Singh, Preeti; Hanson, Peter S; Morris, Christopher M

2017-06-02

Sirtuins (SIRTs) are NAD + dependent lysine deacetylases which are conserved from bacteria to humans and have been associated with longevity and lifespan extension. SIRT1, the best studied mammalian SIRT is involved in many physiological and pathological processes and changes in SIRT1 have been implicated in neurodegenerative disorders, with SIRT1 having a suggested protective role in Parkinson's disease. In this study, we determined the effect of SIRT1 on cell survival and α-synuclein aggregate formation in SH-SY5Y cells following oxidative stress. Over-expression of SIRT1 protected SH-SY5Y cells from toxin induced cell death and the protection conferred by SIRT1 was partially independent of its deacetylase activity, which was associated with the repression of NF-кB and cPARP expression. SIRT1 reduced the formation of α-synuclein aggregates but showed minimal co-localisation with α-synuclein. In post-mortem brain tissue obtained from patients with Parkinson's disease, Parkinson's disease with dementia, dementia with Lewy bodies and Alzheimer's disease, the activity of SIRT1 was observed to be down-regulated. These findings suggests a negative effect of oxidative stress in neurodegenerative disorders and possibly explain the reduced activity of SIRT1 in neurodegenerative disorders. Our study shows that SIRT1 is a pro-survival protein that is downregulated under cellular stress.

Familial Longevity Is Not Associated with Major Differences in the Hypothalamic–Pituitary–Gonadal Axis in Healthy Middle-Aged Men

DEFF Research Database (Denmark)

van der Spoel, Evie; Roelfsema, Ferdinand; Jansen, Steffy W.

2016-01-01

longevity and controls. Design: We frequently sampled blood over 24 h in 10 healthy middle-aged male offspring of nonagenarian participants from the Leiden Longevity Study together with 10 male age-matched controls. Individual 24-h luteinizing hormone (LH) and testosterone concentration profiles were....../feedback regulation within the HPG axis were similar between offspring of long-lived families and controls. Conclusion: This relatively small study suggests that in healthy male middle-aged participants, familial longevity is not associated with major differences in the HPG axis. Selection on both fertility...

Some agricultural aspects of seed longevity (literature review

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Roman Hołubowicz

2013-12-01

Full Text Available There has been a vast and numerous literature concerning seed longevity. Most of these works however has focused solely on theoretical and biological aspects of this problem. Some works although deal with practical problems of seed storage. vigour or deterioration. have had relatively little connection with agricultural crops. practical farming or gardening. Therefore, there has been a need to look at this problem from the seednian's and farmer's point of view. The paper comments on how long seeds of agricultural crops species can keep their longevity, how long it is economically reasonable to store them. the effect of the seeds chemical composition on their longevity, how seeds storage conditions can be modified in order to eventually improve their longevity and environment circumstances influence on the final seed longevity. The paper contains a synthetic summary of expected seed longevity of the most important agricultural species and many examples of long longevity of agricultural species.

Psychological Consequences of Longevity: The Increasing Importance of Self-Regulation in Old Age

Science.gov (United States)

Freund, Alexandra M.; Nikitin, Jana; Ritter, Johannes O.

2009-01-01

How do changes in life expectancy and longevity affect life-span development? This paper argues that historical increases in life expectancy primarily have an impact on the later and less on the earlier parts of the life span. Increased life expectancy is both a challenge and an opportunity for positive development. A perspective is outlined…

Visible light reduces C. elegans longevity.

Science.gov (United States)

De Magalhaes Filho, C Daniel; Henriquez, Brian; Seah, Nicole E; Evans, Ronald M; Lapierre, Louis R; Dillin, Andrew

2018-03-02

The transparent nematode Caenorhabditis elegans can sense UV and blue-violet light to alter behavior. Because high-dose UV and blue-violet light are not a common feature outside of the laboratory setting, we asked what role, if any, could low-intensity visible light play in C. elegans physiology and longevity. Here, we show that C. elegans lifespan is inversely correlated to the time worms were exposed to visible light. While circadian control, lite-1 and tax-2 do not contribute to the lifespan reduction, we demonstrate that visible light creates photooxidative stress along with a general unfolded-protein response that decreases the lifespan. Finally, we find that long-lived mutants are more resistant to light stress, as well as wild-type worms supplemented pharmacologically with antioxidants. This study reveals that transparent nematodes are sensitive to visible light radiation and highlights the need to standardize methods for controlling the unrecognized biased effect of light during lifespan studies in laboratory conditions.

JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks

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Michael Van Meter

2016-09-01

Full Text Available The accumulation of damage caused by oxidative stress has been linked to aging and to the etiology of numerous age-related diseases. The longevity gene, sirtuin 6 (SIRT6, promotes genome stability by facilitating DNA repair, especially under oxidative stress conditions. Here we uncover the mechanism by which SIRT6 is activated by oxidative stress to promote DNA double-strand break (DSB repair. We show that the stress-activated protein kinase, c-Jun N-terminal kinase (JNK, phosphorylates SIRT6 on serine 10 in response to oxidative stress. This post-translational modification facilitates the mobilization of SIRT6 to DNA damage sites and is required for efficient recruitment of poly (ADP-ribose polymerase 1 (PARP1 to DNA break sites and for efficient repair of DSBs. Our results demonstrate a post-translational mechanism regulating SIRT6, and they provide the link between oxidative stress signaling and DNA repair pathways that may be critical for hormetic response and longevity assurance.

Reduced Insulin/IGF-1 Signaling Restores the Dynamic Properties of Key Stress Granule Proteins during Aging

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Marie C. Lechler

2017-01-01

Full Text Available Summary: Low-complexity “prion-like” domains in key RNA-binding proteins (RBPs mediate the reversible assembly of RNA granules. Individual RBPs harboring these domains have been linked to specific neurodegenerative diseases. Although their aggregation in neurodegeneration has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. We show that a wide variety of RNA granule components, including stress granule proteins, become highly insoluble with age in C. elegans and that reduced insulin/insulin-like growth factor 1 (IGF-1 daf-2 receptor signaling efficiently prevents their aggregation. Importantly, stress-granule-related RBP aggregates are associated with reduced fitness. We show that heat shock transcription factor 1 (HSF-1 is a main regulator of stress-granule-related RBP aggregation in both young and aged animals. During aging, increasing DAF-16 activity restores dynamic stress-granule-related RBPs, partly by decreasing the buildup of other misfolded proteins that seed RBP aggregation. Longevity-associated mechanisms found to maintain dynamic RBPs during aging could be relevant for neurodegenerative diseases. : Lechler et al. show that RNA-binding proteins (RBPs including stress granule proteins are prone to aggregate with age in C. elegans. Aggregation of stress granule RBPs with “prion-like” domains is associated with reduced fitness. Their aggregation is prevented by longevity pathways and promoted by the aggregation of other misfolded proteins. Keywords: neurodegenerative diseases, Caenorhabditis elegans, protein aggregation, aging, RNA-binding proteins, stress granules, HSF-1, DAF-2, longevity

Genetics, lifestyle and longevity: Lessons from centenarians

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Diddahally Govindaraju

2015-03-01

Full Text Available Longevity as a complex life-history trait shares an ontogenetic relationship with other quantitative traits and varies among individuals, families and populations. Heritability estimates of longevity suggest that about a third of the phenotypic variation associated with the trait is attributable to genetic factors, and the rest is influenced by epigenetic and environmental factors. Individuals react differently to the environments that they are a part of, as well as to the environments they construct for their survival and reproduction; the latter phenomenon is known as niche construction. Lifestyle influences longevity at all the stages of development and levels of human diversity. Hence, lifestyle may be viewed as a component of niche construction. Here, we: a interpret longevity using a combination of genotype-epigenetic-phenotype (GEP map approach and niche-construction theory, and b discuss the plausible influence of genetic and epigenetic factors in the distribution and maintenance of longevity among individuals with normal life span on the one hand, and centenarians on the other. Although similar genetic and environmental factors appear to be common to both of these groups, exceptional longevity may be influenced by polymorphisms in specific genes, coupled with superior genomic stability and homeostatic mechanisms, maintained by negative frequency-dependent selection. We suggest that a comparative analysis of longevity between individuals with normal life span and centenarians, along with insights from population ecology and evolutionary biology, would not only advance our knowledge of biological mechanisms underlying human longevity, but also provide deeper insights into extending healthy life span.

Genetics, lifestyle and longevity: Lessons from centenarians

Science.gov (United States)

Govindaraju, Diddahally; Atzmon, Gil; Barzilai, Nir

2015-01-01

Longevity as a complex life-history trait shares an ontogenetic relationship with other quantitative traits and varies among individuals, families and populations. Heritability estimates of longevity suggest that about a third of the phenotypic variation associated with the trait is attributable to genetic factors, and the rest is influenced by epigenetic and environmental factors. Individuals react differently to the environments that they are a part of, as well as to the environments they construct for their survival and reproduction; the latter phenomenon is known as niche construction. Lifestyle influences longevity at all the stages of development and levels of human diversity. Hence, lifestyle may be viewed as a component of niche construction. Here, we: a) interpret longevity using a combination of genotype-epigenetic-phenotype (GEP) map approach and niche-construction theory, and b) discuss the plausible influence of genetic and epigenetic factors in the distribution and maintenance of longevity among individuals with normal life span on the one hand, and centenarians on the other. Although similar genetic and environmental factors appear to be common to both of these groups, exceptional longevity may be influenced by polymorphisms in specific genes, coupled with superior genomic stability and homeostatic mechanisms, maintained by negative frequency-dependent selection. We suggest that a comparative analysis of longevity between individuals with normal life span and centenarians, along with insights from population ecology and evolutionary biology, would not only advance our knowledge of biological mechanisms underlying human longevity, but also provide deeper insights into extending healthy life span. PMID:26937346

Genetics of human longevity with emphasis on the relevance of HSP70 as candidate genes

DEFF Research Database (Denmark)

Singh, Ripudaman; Kølvrå, Steen; Rattan, Suresh I S

2007-01-01

Human longevity is determined to a certain extent by genetic factors. Several candidate genes have been studied for their association with human longevity, but the data collected so far are inconclusive. One of the reasons is the choice of the candidate genes in addition to the choice...... of an appropriate study design and methodology. Since aging is characterized by a progressive accumulation of molecular damage and an attenuation of the cellular defense mechanisms, the focus of studies on human longevity association with genes has now shifted to the pathways of cellular maintenance and repair...... mechanisms. One such pathway includes the battery of stress response genes, especially the heat shock protein HSP70 genes. Three such genes, HSPA1A, HSPA1B and HSPA1L, are present within the MHC-III region on the short arm of chromosome 6. We and others have found alleles, genotypes and haplotypes which have...

The influence of acute stress on the regulation of conditioned fear

Directory of Open Access Journals (Sweden)

Candace M. Raio

2015-01-01

Full Text Available Fear learning and regulation is a prominent model for describing the pathogenesis of anxiety disorders and stress-related psychopathology. Fear expression can be modulated using a number of regulatory strategies, including extinction, cognitive emotion regulation, avoidance strategies and reconsolidation. In this review, we examine research investigating the effects of acute stress and stress hormones on these regulatory techniques. We focus on what is known about the impact of stress on the ability to flexibly regulate fear responses that are acquired through Pavlovian fear conditioning. Our primary aim is to explore the impact of stress on fear regulation in humans. Given this, we focus on techniques where stress has been linked to alterations of fear regulation in humans (extinction and emotion regulation, and briefly discuss other techniques (avoidance and reconsolidation where the impact of stress or stress hormones have been mainly explored in animal models. These investigations reveal that acute stress may impair the persistent inhibition of fear, presumably by altering prefrontal cortex function. Characterizing the effects of stress on fear regulation is critical for understanding the boundaries within which existing regulation strategies are viable in everyday life and can better inform treatment options for those who suffer from anxiety and stress-related psychopathology.

Stress-induced self-cannibalism: on the regulation of autophagy by endoplasmic reticulum stress.

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Deegan, Shane; Saveljeva, Svetlana; Gorman, Adrienne M; Samali, Afshin

2013-07-01

Macroautophagy (autophagy) is a cellular catabolic process which can be described as a self-cannibalism. It serves as an essential protective response during conditions of endoplasmic reticulum (ER) stress through the bulk removal and degradation of unfolded proteins and damaged organelles; in particular, mitochondria (mitophagy) and ER (reticulophagy). Autophagy is genetically regulated and the autophagic machinery facilitates removal of damaged cell components and proteins; however, if the cell stress is acute or irreversible, cell death ensues. Despite these advances in the field, very little is known about how autophagy is initiated and how the autophagy machinery is transcriptionally regulated in response to ER stress. Some three dozen autophagy genes have been shown to be required for the correct assembly and function of the autophagic machinery; however; very little is known about how these genes are regulated by cellular stress. Here, we will review current knowledge regarding how ER stress and the unfolded protein response (UPR) induce autophagy, including description of the different autophagy-related genes which are regulated by the UPR.

The DAF-16 FOXO transcription factor regulates natc-1 to modulate stress resistance in Caenorhabditis elegans, linking insulin/IGF-1 signaling to protein N-terminal acetylation.

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Warnhoff, Kurt; Murphy, John T; Kumar, Sandeep; Schneider, Daniel L; Peterson, Michelle; Hsu, Simon; Guthrie, James; Robertson, J David; Kornfeld, Kerry

2014-10-01

The insulin/IGF-1 signaling pathway plays a critical role in stress resistance and longevity, but the mechanisms are not fully characterized. To identify genes that mediate stress resistance, we screened for C. elegans mutants that can tolerate high levels of dietary zinc. We identified natc-1, which encodes an evolutionarily conserved subunit of the N-terminal acetyltransferase C (NAT) complex. N-terminal acetylation is a widespread modification of eukaryotic proteins; however, relatively little is known about the biological functions of NATs. We demonstrated that loss-of-function mutations in natc-1 cause resistance to a broad-spectrum of physiologic stressors, including multiple metals, heat, and oxidation. The C. elegans FOXO transcription factor DAF-16 is a critical target of the insulin/IGF-1 signaling pathway that mediates stress resistance, and DAF-16 is predicted to directly bind the natc-1 promoter. To characterize the regulation of natc-1 by DAF-16 and the function of natc-1 in insulin/IGF-1 signaling, we analyzed molecular and genetic interactions with key components of the insulin/IGF-1 pathway. natc-1 mRNA levels were repressed by DAF-16 activity, indicating natc-1 is a physiological target of DAF-16. Genetic studies suggested that natc-1 functions downstream of daf-16 to mediate stress resistance and dauer formation. Based on these findings, we hypothesize that natc-1 is directly regulated by the DAF-16 transcription factor, and natc-1 is a physiologically significant effector of the insulin/IGF-1 signaling pathway that mediates stress resistance and dauer formation. These studies identify a novel biological function for natc-1 as a modulator of stress resistance and dauer formation and define a functionally significant downstream effector of the insulin/IGF-1 signaling pathway. Protein N-terminal acetylation mediated by the NatC complex may play an evolutionarily conserved role in regulating stress resistance.

Of Malthus and Methuselah: does longevity treatment aggravate global catastrophic risks?

International Nuclear Information System (INIS)

Jebari, Karim

2014-01-01

Global catastrophic risk is a term that refers to the risk of the occurrence of an event that kills at least millions of people across several continents. While it has been argued by a number of scholars that one major potential risk comes from technology, the obscure nature of future technologies makes it difficult to utilize traditional probabilistic risk for the meaningful study of these risks. This article describes an alternative approach and applies it to a research program that has attracted a considerable amount of resources recently: namely longevity research. The aim of this research is to delay or reverse the ageing process. This article argues that this research program is much more risky or less beneficial than its proponents argue. In particular, they tend to underestimate the concerns associated with the potentially drastic population growth that longevity treatment could cause. The ethical benefit often ascribed to longevity treatment is that such treatment would add more subjective life-years that are worth living. However, in light of contemporary environmental problems, such an increase of the human population might be reckless. Drastically reducing fertility to reduce risks associated with environmental stress would make the benefits of such technology much less compelling. (invited comment)

Of Malthus and Methuselah: does longevity treatment aggravate global catastrophic risks?

Science.gov (United States)

Jebari, Karim

2014-12-01

Global catastrophic risk is a term that refers to the risk of the occurrence of an event that kills at least millions of people across several continents. While it has been argued by a number of scholars that one major potential risk comes from technology, the obscure nature of future technologies makes it difficult to utilize traditional probabilistic risk for the meaningful study of these risks. This article describes an alternative approach and applies it to a research program that has attracted a considerable amount of resources recently: namely longevity research. The aim of this research is to delay or reverse the ageing process. This article argues that this research program is much more risky or less beneficial than its proponents argue. In particular, they tend to underestimate the concerns associated with the potentially drastic population growth that longevity treatment could cause. The ethical benefit often ascribed to longevity treatment is that such treatment would add more subjective life-years that are worth living. However, in light of contemporary environmental problems, such an increase of the human population might be reckless. Drastically reducing fertility to reduce risks associated with environmental stress would make the benefits of such technology much less compelling.

Genetics of healthy aging and longevity.

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Brooks-Wilson, Angela R

2013-12-01

Longevity and healthy aging are among the most complex phenotypes studied to date. The heritability of age at death in adulthood is approximately 25 %. Studies of exceptionally long-lived individuals show that heritability is greatest at the oldest ages. Linkage studies of exceptionally long-lived families now support a longevity locus on chromosome 3; other putative longevity loci differ between studies. Candidate gene studies have identified variants at APOE and FOXO3A associated with longevity; other genes show inconsistent results. Genome-wide association scans (GWAS) of centenarians vs. younger controls reveal only APOE as achieving genome-wide significance (GWS); however, analyses of combinations of SNPs or genes represented among associations that do not reach GWS have identified pathways and signatures that converge upon genes and biological processes related to aging. The impact of these SNPs, which may exert joint effects, may be obscured by gene-environment interactions or inter-ethnic differences. GWAS and whole genome sequencing data both show that the risk alleles defined by GWAS of common complex diseases are, perhaps surprisingly, found in long-lived individuals, who may tolerate them by means of protective genetic factors. Such protective factors may 'buffer' the effects of specific risk alleles. Rare alleles are also likely to contribute to healthy aging and longevity. Epigenetics is quickly emerging as a critical aspect of aging and longevity. Centenarians delay age-related methylation changes, and they can pass this methylation preservation ability on to their offspring. Non-genetic factors, particularly lifestyle, clearly affect the development of age-related diseases and affect health and lifespan in the general population. To fully understand the desirable phenotypes of healthy aging and longevity, it will be necessary to examine whole genome data from large numbers of healthy long-lived individuals to look simultaneously at both common and

Sex differences in cognitive regulation of psychosocial achievement stress: brain and behavior.

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Kogler, Lydia; Gur, Ruben C; Derntl, Birgit

2015-03-01

Although cognitive regulation of emotion has been extensively examined, there is a lack of studies assessing cognitive regulation in stressful achievement situations. This study used functional magnetic resonance imaging in 23 females and 20 males to investigate cognitive downregulation of negative, stressful sensations during a frequently used psychosocial stress task. Additionally, subjective responses, cognitive regulation strategies, salivary cortisol, and skin conductance response were assessed. Subjective response supported the experimental manipulation by showing higher anger and negative affect ratings after stress regulation than after the mere exposure to stress. On a neural level, right middle frontal gyrus (MFG) and right superior temporal gyrus (STG) were more strongly activated during regulation than nonregulation, whereas the hippocampus was less activated during regulation. Sex differences were evident: after regulation females expressed higher subjective stress ratings than males, and these ratings were associated with right hippocampal activation. In the nonregulation block, females showed greater activation of the left amygdala and the right STG during stress than males while males recruited the putamen more robustly in this condition. Thus, cognitive regulation of stressful achievement situations seems to induce additional stress, to recruit regions implicated in attention integration and working memory and to deactivate memory retrieval. Stress itself is associated with greater activation of limbic as well as attention areas in females than males. Additionally, activation of the memory system during cognitive regulation of stress is associated with greater perceived stress in females. Sex differences in cognitive regulation strategies merit further investigation that can guide sex sensitive interventions for stress-associated disorders. © 2014 Wiley Periodicals, Inc.

The lysosomal membrane protein SCAV-3 maintains lysosome integrity and adult longevity

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Li, Yuan; Chen, Baohui; Zou, Wei; Wang, Xin; Wu, Yanwei; Zhao, Dongfeng; Sun, Yanan; Liu, Yubing

2016-01-01

Lysosomes degrade macromolecules and recycle metabolites as well as being involved in diverse processes that regulate cellular homeostasis. The lysosome is limited by a single phospholipid bilayer that forms a barrier to separate the potent luminal hydrolases from other cellular constituents, thus protecting the latter from unwanted degradation. The mechanisms that maintain lysosomal membrane integrity remain unknown. Here, we identified SCAV-3, the Caenorhabditis elegans homologue of human LIMP-2, as a key regulator of lysosome integrity, motility, and dynamics. Loss of scav-3 caused rupture of lysosome membranes and significantly shortened lifespan. Both of these phenotypes were suppressed by reinforced expression of LMP-1 or LMP-2, the C. elegans LAMPs, indicating that longevity requires maintenance of lysosome integrity. Remarkably, reduction in insulin/insulin-like growth factor 1 (IGF-1) signaling suppressed lysosomal damage and extended the lifespan in scav-3(lf) animals in a DAF-16–dependent manner. Our data reveal that SCAV-3 is essential for preserving lysosomal membrane stability and that modulation of lysosome integrity by the insulin/IGF-1 signaling pathway affects longevity. PMID:27810910

Understanding the natural and social factors behind regional longevity in Guangxi, China—Is centenarian ratio a good enough indicator for assessing the longevity level?

Science.gov (United States)

Deng, Q.; Wei, Y.; Zhao, Y.

2017-12-01

Despite a number of longevity indicators having been used in previous longevity studies, few studies have critically evaluated whether these indicators are suitable. In addition, an increasing number of studies have attempted to determine the influence of socio-economic and natural factors on regional longevity, but only certain factors were considered. The present study bridges this gap by determining the relationship between the seven longevity indicators and selecting 24 natural and socio-economic indicators in the 91 selected counties and districts in Guangxi, China. The seven longevity indicators here refer to Centenarian ratio, Longevity index, Longevity level, Aging tendency, 80+ ratio, 90+ ratio and 95+ ratio. Natural indicators in this study mainly refer to climatic ones. Socio-economic indicators can be categorized into those related to economic, education, local infrastructure, and health care facilities. These data were mainly drawn from the Meteorological Data Sharing Service System and Guangxi's sixth population census. Stepwise regression analysis has been used as the primary research method to determine the relationship between the longevity indicators and the natural, social, and economic indicators. The results show that the climate factors regarding atmospheric pressure, humidity, and rainfall are the most significant contributors to the longevity of the 60- to 90-year-old elderly in Guangxi, while the difference of mean annual temperature could have negative impacts. Also, the natural and socioeconomic factors that impact the extremely old population (those over 95 years old) in Guangxi are still not clear. This study reveals that the longevity index and longevity level are useful supplementary indexes to the centenarian ratio for assessing the regional longevity as they could help reflect the regional longevity regarding the proportion of young-old and old-old population and not just limit to those over 100 years old. The elderly (those from 60

Classification for longevity potential: the use of novel biomarkers

Directory of Open Access Journals (Sweden)

Marian Beekman

2016-10-01

Full Text Available Background: In older people chronological age may not be the best predictor of residual lifespan and mortality, because with age the heterogeneity in health is increasing. Biomarkers for biological age and residual lifespan are being developed to predict disease and mortality better at an individual level than chronological age. In the current paper we aim to classify a group of older people into those with longevity potential or controls.Methods: In the Leiden Longevity Study participated 1671 offspring of nonagenarian siblings, as the group with longevity potential, and 744 similarly aged controls. Using known risk factors for cardiovascular disease, previously reported markers for human longevity and other physiological measures as predictors, classification models for longevity potential were constructed with multiple logistic regression of the offspring-control status.Results: The Framingham Risk Score is predictive for longevity potential (AUC = 64.7. Physiological parameters involved in immune responses and glucose, lipid and energy metabolism further improve the prediction performance for longevity potential (AUCmale = 71.4, AUCfemale = 68.7.Conclusion: Using the Framingham Risk Score, the classification of older people in groups with longevity potential and controls is moderate, but can be improved to a reasonably good classification in combination with markers of immune response, glucose, lipid and energy metabolism. We show that individual classification of older people for longevity potential may be feasible using biomarkers from a wide variety of different biological processes.

Typologies of extreme longevity myths.

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Young, Robert D; Desjardins, Bertrand; McLaughlin, Kirsten; Poulain, Michel; Perls, Thomas T

2010-01-01

Purpose. Political, national, religious, and other motivations have led the media and even scientists to errantly accept extreme longevity claims prima facie. We describe various causes of false claims of extraordinary longevity. Design and Methods. American Social Security Death Index files for the period 1980-2009 were queried for individuals with birth and death dates yielding ages 110+ years of age. Frequency was compared to a list of age-validated supercentenarians maintained by the Gerontology Research Group who died during the same time period. Age claims of 110+ years and the age validation experiences of the authors facilitated a list of typologies of false age claims. Results. Invalid age claim rates increase with age from 65% at age 110-111 to 98% by age 115 to 100% for 120+ years. Eleven typologies of false claims were: Religious Authority Myth, Village Elder Myth, Fountain of Youth Myth (substance), Shangri-La Myth (geographic), Nationalist Pride, Spiritual Practice, Familial Longevity, Individual and/or Family Notoriety, Military Service, Administrative Entry Error, and Pension-Social Entitlement Fraud. Conclusions. Understanding various causes of false extreme age claims is important for placing current, past, and future extreme longevity claims in context and for providing a necessary level of skepticism.

Typologies of Extreme Longevity Myths

Directory of Open Access Journals (Sweden)

Robert D. Young

2010-01-01

Full Text Available Purpose. Political, national, religious, and other motivations have led the media and even scientists to errantly accept extreme longevity claims prima facie. We describe various causes of false claims of extraordinary longevity. Design and Methods. American Social Security Death Index files for the period 1980–2009 were queried for individuals with birth and death dates yielding ages 110+ years of age. Frequency was compared to a list of age-validated supercentenarians maintained by the Gerontology Research Group who died during the same time period. Age claims of 110+ years and the age validation experiences of the authors facilitated a list of typologies of false age claims. Results. Invalid age claim rates increase with age from 65% at age 110-111 to 98% by age 115 to 100% for 120+ years. Eleven typologies of false claims were: Religious Authority Myth, Village Elder Myth, Fountain of Youth Myth (substance, Shangri-La Myth (geographic, Nationalist Pride, Spiritual Practice, Familial Longevity, Individual and/or Family Notoriety, Military Service, Administrative Entry Error, and Pension-Social Entitlement Fraud. Conclusions. Understanding various causes of false extreme age claims is important for placing current, past, and future extreme longevity claims in context and for providing a necessary level of skepticism.

Autonomous orientation predicts longevity: New findings from the Nun Study.

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Weinstein, Netta; Legate, Nicole; Ryan, William S; Hemmy, Laura

2018-03-10

Work on longevity has found protective social, cognitive, and emotional factors, but to date we have little understanding of the impact of motivational dynamics. Autonomy orientation, or stable patterns of self-regulation, is theorized to be a protective factor for long-term mental and physical health (Ryan & Deci, 2017), and it is therefore a prime candidate for examining how stable psychosocial factors are linked to longevity, or life expectancy. Essays written in the 1930s by participants in the Nun Study were coded for indicators of an autonomy orientation. These were selected in line with an extensive theoretical literature based in self-determination theory (Deci & Ryan, 1985). Essays were coded for the propensity for choice in action, susceptibility to pressure, self-reflection, integration of experiences, and parental support for autonomy. These coded variables were used to predict age of death. Using 176 codable essays provided by now-deceased participants, linear regression analyses revealed that choiceful behavior, self-reflection, and parent autonomy support predicted age of death. Participants who demonstrated these stable and beneficial motivational characteristics lived longer. Personality constructs reflecting a healthy form of self-regulation are associated with long-term health. Implications for health interventions are discussed. © 2018 The Authors. Journal of Personality Published by Wiley Periodicals, Inc.

Intergenerational redistribution and risk sharing with changing longevity

DEFF Research Database (Denmark)

Andersen, Torben M.

2014-01-01

Trend increases in longevity are a global phenomenon challenging the fiscal sustainability of current welfare arrangements. Policy proposals abound and often build on implicit assertions concerning intergenerational equity. This paper offers a simple but manageable OLG model with endogenous retir...... to have a high longevity are compensated at the expense of cohorts turning out to have a relatively short longevity....

Aging, longevity and health

DEFF Research Database (Denmark)

Rasmussen, Lene Juel; Sander, Miriam; Wewer, Ulla M.

2011-01-01

The IARU Congress on Aging, Longevity and Health, held on 5-7 October 2010 in Copenhagen, Denmark, was hosted by Rector Ralf Hemmingsen, University of Copenhagen and Dean Ulla Wewer, Faculty of Health Sciences, University of Copenhagen and was organized by Center for Healthy Aging (CEHA) under......, Muscle and Life Span and Life Span and Mechanisms. Two additional Sessions highlighted ongoing research in the recently established Center for Healthy Aging at the University of Copenhagen. This report highlights outcomes of recent research on aging-related topics, as described at the IARU Congress...... on Aging, Longevity and Health....

The Ratio of Macronutrients, Not Caloric Intake, Dictates Cardiometabolic Health, Aging, and Longevity in Ad Libitum-Fed Mice

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Solon-Biet, Samantha M.; McMahon, Aisling C.; Ballard, J. William O.; Ruohonen, Kari; Wu, Lindsay E.; Cogger, Victoria C.; Warren, Alessandra; Huang, Xin; Pichaud, Nicolas; Melvin, Richard G.; Gokarn, Rahul; Khalil, Mamdouh; Turner, Nigel; Cooney, Gregory J.; Sinclair, David A.; Raubenheimer, David; Le Couteur, David G.; Simpson, Stephen J.

2016-01-01

Summary The fundamental questions of what represents a macronutritionally balanced diet and how this maintains health and longevity remain unanswered. Here, the Geometric Framework, a state-space nutritional modeling method, was used to measure interactive effects of dietary energy, protein, fat, and carbohydrate on food intake, cardiometabolic phenotype, and longevity in mice fed one of 25 diets ad libitum. Food intake was regulated primarily by protein and carbohydrate content. Longevity and health were optimized when protein was replaced with carbohydrate to limit compensatory feeding for protein and suppress protein intake. These consequences are associated with hepatic mammalian target of rapamycin (mTOR) activation and mitochondrial function and, in turn, related to circulating branched-chain amino acids and glucose. Calorie restriction achieved by high-protein diets or dietary dilution had no beneficial effects on lifespan. The results suggest that longevity can be extended in ad libitum-fed animals by manipulating the ratio of macronutrients to inhibit mTOR activation. PMID:24606899

A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice.

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Roberts, Megan N; Wallace, Marita A; Tomilov, Alexey A; Zhou, Zeyu; Marcotte, George R; Tran, Dianna; Perez, Gabriella; Gutierrez-Casado, Elena; Koike, Shinichiro; Knotts, Trina A; Imai, Denise M; Griffey, Stephen M; Kim, Kyoungmi; Hagopian, Kevork; McMackin, Marissa Z; Haj, Fawaz G; Baar, Keith; Cortopassi, Gino A; Ramsey, Jon J; Lopez-Dominguez, Jose Alberto

2017-09-05

Calorie restriction, without malnutrition, has been shown to increase lifespan and is associated with a shift away from glycolysis toward beta-oxidation. The objective of this study was to mimic this metabolic shift using low-carbohydrate diets and to determine the influence of these diets on longevity and healthspan in mice. C57BL/6 mice were assigned to a ketogenic, low-carbohydrate, or control diet at 12 months of age and were either allowed to live their natural lifespan or tested for physiological function after 1 or 14 months of dietary intervention. The ketogenic diet (KD) significantly increased median lifespan and survival compared to controls. In aged mice, only those consuming a KD displayed preservation of physiological function. The KD increased protein acetylation levels and regulated mTORC1 signaling in a tissue-dependent manner. This study demonstrates that a KD extends longevity and healthspan in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

The rate of metabolism as a factor determining longevity of the Saccharomyces cerevisiae yeast.

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Molon, Mateusz; Szajwaj, Monika; Tchorzewski, Marek; Skoczowski, Andrzej; Niewiadomska, Ewa; Zadrag-Tecza, Renata

2016-02-01

Despite many controversies, the yeast Saccharomyces cerevisiae continues to be used as a model organism for the study of aging. Numerous theories and hypotheses have been created for several decades, yet basic mechanisms of aging have remained unclear. Therefore, the principal aim of this work is to propose a possible mechanism leading to increased longevity in yeast. In this paper, we suggest for the first time that there is a link between decreased metabolic activity, fertility and longevity expressed as time of life in yeast. Determination of reproductive potential and total lifespan with the use of fob1Δ and sfp1Δ mutants allows us to compare the "longevity" presented as the number of produced daughters with the longevity expressed as the time of life. The results of analyses presented in this paper suggest the need for a change in the definition of longevity of yeast by taking into consideration the time parameter. The mutants that have been described as "long-lived" in the literature, such as the fob1Δ mutant, have an increased reproductive potential but live no longer than their standard counterparts. On the other hand, the sfp1Δ mutant and the wild-type strain produce a similar number of daughter cells, but the former lives much longer. Our results demonstrate a correlation between the decreased efficiency of the translational apparatus and the longevity of the sfp1Δ mutant. We suggest that a possible factor regulating the lifespan is the rate of cell metabolism. To measure the basic metabolism of the yeast cells, we used the isothermal microcalorimetry method. In the case of sfp1Δ, the flow of energy, ATP concentration, polysome profile and translational fitness are significantly lower in comparison with the wild-type strain and the fob1Δ mutant.

Masculine Discrepancy Stress, Emotion-Regulation Difficulties, and Intimate Partner Violence.

Science.gov (United States)

Berke, Danielle S; Reidy, Dennis E; Gentile, Brittany; Zeichner, Amos

2016-05-24

Research suggests that masculine socialization processes contribute to the perpetration of intimate partner violence (IPV) by men. Although this research has traditionally focused on men who strongly adhere to traditional gender norms, men who negatively evaluate themselves as falling short of these norms (a construct termed masculine discrepancy stress) have proven to be at increased risk of IPV perpetration. Likewise, men experiencing problems with emotion regulation, a multidimensional construct reflecting difficulties in effectively experiencing and responding to emotional states, are also at risk of IPV perpetration. In the present research, we tested the hypothesis that the link between discrepancy stress and IPV perpetration is mediated via difficulties in emotion regulation. Three hundred fifty-seven men completed online surveys assessing their experience of discrepancy stress, emotion-regulation difficulties, and history of IPV perpetration. Results indicated that discrepancy-stressed men's use of physical IPV was fully mediated by emotion-regulation difficulties. In addition, emotion-regulation difficulties partially mediated the association between discrepancy stress and sexual IPV. Findings are discussed in terms of the potential utility of emotion-focused interventions for modifying men's experience and expression of discrepancy stress and reducing perpetration of IPV. © The Author(s) 2016.

Masculine Discrepancy Stress, Emotion-Regulation Difficulties, and Intimate Partner Violence

Science.gov (United States)

Berke, Danielle S.; Reidy, Dennis E.; Gentile, Brittany; Zeichner, Amos

2018-01-01

Research suggests that masculine socialization processes contribute to the perpetration of intimate partner violence (IPV) by men. Although this research has traditionally focused on men who strongly adhere to traditional gender norms, men who negatively evaluate themselves as falling short of these norms (a construct termed masculine discrepancy stress) have proven to be at increased risk of IPV perpetration. Likewise, men experiencing problems with emotion regulation, a multidimensional construct reflecting difficulties in effectively experiencing and responding to emotional states, are also at risk of IPV perpetration. In the present research, we tested the hypothesis that the link between discrepancy stress and IPV perpetration is mediated via difficulties in emotion regulation. Three hundred fifty-seven men completed online surveys assessing their experience of discrepancy stress, emotion-regulation difficulties, and history of IPV perpetration. Results indicated that discrepancy-stressed men's use of physical IPV was fully mediated by emotion-regulation difficulties. In addition, emotion-regulation difficulties partially mediated the association between discrepancy stress and sexual IPV. Findings are discussed in terms of the potential utility of emotion-focused interventions for modifying men's experience and expression of discrepancy stress and reducing perpetration of IPV. PMID:27226013

Metabolomic analysis of the selection response of Drosophila melanogaster to environmental stress

DEFF Research Database (Denmark)

Malmendal, Anders; Sørensen, Jesper Givskov; Overgaard, Johannes

2013-01-01

-regulated in response to selection for some of the stresses in this study. Overall, the results illustrate that selection markedly alters the metabolite profile and that the coupling between different levels of biological organization indeed is present though not very strong for stress selection at this level......We investigated the global metabolite response to artificial selection for tolerance to stressful conditions such as cold, heat, starvation, and desiccation, and for longevity in Drosophila melanogaster. Our findings were compared to data from other levels of biological organization, including gene...... expression, physiological traits, and organismal stress tolerance phenotype. Overall, we found that selection for environmental stress tolerance changes the metabolomic (1)H NMR fingerprint largely in a similar manner independent of the trait selected for, indicating that experimental evolution led...

The crucial impact of lysosomes in aging and longevity.

Science.gov (United States)

Carmona-Gutierrez, Didac; Hughes, Adam L; Madeo, Frank; Ruckenstuhl, Christoph

2016-12-01

Lysosomes are the main catabolic organelles of a cell and play a pivotal role in a plethora of cellular processes, including responses to nutrient availability and composition, stress resistance, programmed cell death, plasma membrane repair, development, and cell differentiation. In line with this pleiotropic importance for cellular and organismal life and death, lysosomal dysfunction is associated with many age-related pathologies like Parkinson's and Alzheimer's disease, as well as with a decline in lifespan. Conversely, targeting lysosomal functional capacity is emerging as a means to promote longevity. Here, we analyze the current knowledge on the prominent influence of lysosomes on aging-related processes, such as their executory and regulatory roles during general and selective macroautophagy, or their storage capacity for amino acids and ions. In addition, we review and discuss the roles of lysosomes as active players in the mechanisms underlying known lifespan-extending interventions like, for example, spermidine or rapamycin administration. In conclusion, this review aims at critically examining the nature and pliability of the different layers, in which lysosomes are involved as a control hub for aging and longevity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Reproduction alters oxidative status when it is traded-off against longevity.

Science.gov (United States)

Beaulieu, Michaël; Geiger, Rina E; Reim, Elisabeth; Zielke, Luisa; Fischer, Klaus

2015-07-01

Oxidative stress has been proposed to mediate one of the most important aspects of life-history evolution: the trade-off between reproduction and self-maintenance. However, empirical studies have cast doubt on the generality of this intriguing notion. Here, we hypothesize that reproduction alters oxidative status only when a trade-off between reproduction and self-maintenance occurs. Accordingly, in female Bicyclus anynana butterflies, we found that reproduction affected oxidative markers only under challenging thermal conditions that made the trade-off between reproduction and longevity emerge. Interestingly, under such conditions, butterflies favored longevity over reproduction, suggesting that self-maintenance mechanisms were activated. Accordingly, butterflies reproducing under challenging thermal conditions exhibited enhanced antioxidant defenses and stable oxidative damage. Altogether, our results indicate that a trade-off between reproduction and self-maintenance is indeed a necessary condition for reproduction to alter oxidative status, and that the effects of such a trade-off on oxidative status depend on whether priority is given to self-maintenance or reproduction. Assessing the existence of the trade-off between self-maintenance and reproduction, and whether self-maintenance is prioritized relative to reproduction is therefore crucial for understanding variation in oxidative status in reproducing animals, which may clarify the general implication of oxidative stress in the resolution of life-history trade-offs. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Genome-wide linkage analysis for human longevity

DEFF Research Database (Denmark)

Beekman, Marian; Blanché, Hélène; Perola, Markus

2013-01-01

Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian...

Bioeconomic evaluation of sow longevity and profitability.

Science.gov (United States)

Rodriguez-Zas, S L; Southey, B R; Knox, R V; Connor, J F; Lowe, J F; Roskamp, B J

2003-12-01

Sow production indicators, including litter size, litter weight, and the length of time that sows remained in the herd (sow longevity), were used to characterize sow performance and profitability. Sow longevity and production records from 148,568 sows in 32 commercial herds from Central Illinois from January 1995 to May 2001 were analyzed using survival and repeatability models, respectively. The factors studied included sow genetics (32 genetic lines), with eight major lines present in multiple herds, and the combination of herd and year of entry in the herd. The largest difference in longevity between the major genetic lines was approximately one parity. There were differences (P present value per sow (present value of future cash flows and the present value of the sow) was used to evaluate the effect of sow longevity and production traits on economic returns. Assuming a zero discount rate per parity, genetic lines with longer herd life resulted in greater profit than genetic lines with shorter herd life. This difference was reduced with increasing discount rates and was reversed with high discount rates and low net income per litter. These results suggest that the magnitude of the economic improvement attained through the use of sow genetic lines with longer longevity depends on the economic context under which the evaluation is made.

The DAF-16 FOXO transcription factor regulates natc-1 to modulate stress resistance in Caenorhabditis elegans, linking insulin/IGF-1 signaling to protein N-terminal acetylation.

Directory of Open Access Journals (Sweden)

Kurt Warnhoff

2014-10-01

Full Text Available The insulin/IGF-1 signaling pathway plays a critical role in stress resistance and longevity, but the mechanisms are not fully characterized. To identify genes that mediate stress resistance, we screened for C. elegans mutants that can tolerate high levels of dietary zinc. We identified natc-1, which encodes an evolutionarily conserved subunit of the N-terminal acetyltransferase C (NAT complex. N-terminal acetylation is a widespread modification of eukaryotic proteins; however, relatively little is known about the biological functions of NATs. We demonstrated that loss-of-function mutations in natc-1 cause resistance to a broad-spectrum of physiologic stressors, including multiple metals, heat, and oxidation. The C. elegans FOXO transcription factor DAF-16 is a critical target of the insulin/IGF-1 signaling pathway that mediates stress resistance, and DAF-16 is predicted to directly bind the natc-1 promoter. To characterize the regulation of natc-1 by DAF-16 and the function of natc-1 in insulin/IGF-1 signaling, we analyzed molecular and genetic interactions with key components of the insulin/IGF-1 pathway. natc-1 mRNA levels were repressed by DAF-16 activity, indicating natc-1 is a physiological target of DAF-16. Genetic studies suggested that natc-1 functions downstream of daf-16 to mediate stress resistance and dauer formation. Based on these findings, we hypothesize that natc-1 is directly regulated by the DAF-16 transcription factor, and natc-1 is a physiologically significant effector of the insulin/IGF-1 signaling pathway that mediates stress resistance and dauer formation. These studies identify a novel biological function for natc-1 as a modulator of stress resistance and dauer formation and define a functionally significant downstream effector of the insulin/IGF-1 signaling pathway. Protein N-terminal acetylation mediated by the NatC complex may play an evolutionarily conserved role in regulating stress resistance.

How Do Stress Exposure and Stress Regulation Relate to Borderline Personality Disorder?

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Nadège Bourvis

2017-11-01

Full Text Available Borderline personality disorder (BPD is a severe and frequent disorder characterized by a pervasive pattern of instability affecting impulse control, emotional regulation, cognitive processing, self-image and interpersonal relationships. Patients’ personal histories are often marked by stressful or traumatic experiences, either unique or repeated. Moreover, while clinical signs of the disorder include both chronic and acute features, acute features are mostly triggered by acute stressful situations. Such features include transient cognitive distortion, intense anger, uncontrollable impulsivity, and self-harm behavior – including suicide – and contribute to the burden of the disease. In this paper, we review the various aspects (epidemiological, clinical, and physiological contributing to the relationship between BDP and stress. In particular, we explore the statistical association between stress exposure and the emergence of BPD while taking into account other psychopathologies, such as post-traumatic stress disorder. Then, the different aspects of stress responses (namely, the phenomenological, behavioral, hormonal, neuro-vegetative and neural responses are reviewed in BPD patients. Pathophysiological hypotheses are formulated to explain the differences in responses between BPD patients and healthy subjects and their relation to BPD symptoms. Although the pathogenesis remains uncertain, our conclusions seem to reflect a specific biological and neural pattern of altered stress perception and regulation in BPD.

How Do Stress Exposure and Stress Regulation Relate to Borderline Personality Disorder?

Science.gov (United States)

Bourvis, Nadège; Aouidad, Aveline; Cabelguen, Clémence; Cohen, David; Xavier, Jean

2017-01-01

Borderline personality disorder (BPD) is a severe and frequent disorder characterized by a pervasive pattern of instability affecting impulse control, emotional regulation, cognitive processing, self-image and interpersonal relationships. Patients' personal histories are often marked by stressful or traumatic experiences, either unique or repeated. Moreover, while clinical signs of the disorder include both chronic and acute features, acute features are mostly triggered by acute stressful situations. Such features include transient cognitive distortion, intense anger, uncontrollable impulsivity, and self-harm behavior - including suicide - and contribute to the burden of the disease. In this paper, we review the various aspects (epidemiological, clinical, and physiological) contributing to the relationship between BDP and stress. In particular, we explore the statistical association between stress exposure and the emergence of BPD while taking into account other psychopathologies, such as post-traumatic stress disorder. Then, the different aspects of stress responses (namely, the phenomenological, behavioral, hormonal, neuro-vegetative and neural responses) are reviewed in BPD patients. Pathophysiological hypotheses are formulated to explain the differences in responses between BPD patients and healthy subjects and their relation to BPD symptoms. Although the pathogenesis remains uncertain, our conclusions seem to reflect a specific biological and neural pattern of altered stress perception and regulation in BPD.

How Do Stress Exposure and Stress Regulation Relate to Borderline Personality Disorder?

Science.gov (United States)

Bourvis, Nadège; Aouidad, Aveline; Cabelguen, Clémence; Cohen, David; Xavier, Jean

2017-01-01

Borderline personality disorder (BPD) is a severe and frequent disorder characterized by a pervasive pattern of instability affecting impulse control, emotional regulation, cognitive processing, self-image and interpersonal relationships. Patients’ personal histories are often marked by stressful or traumatic experiences, either unique or repeated. Moreover, while clinical signs of the disorder include both chronic and acute features, acute features are mostly triggered by acute stressful situations. Such features include transient cognitive distortion, intense anger, uncontrollable impulsivity, and self-harm behavior – including suicide – and contribute to the burden of the disease. In this paper, we review the various aspects (epidemiological, clinical, and physiological) contributing to the relationship between BDP and stress. In particular, we explore the statistical association between stress exposure and the emergence of BPD while taking into account other psychopathologies, such as post-traumatic stress disorder. Then, the different aspects of stress responses (namely, the phenomenological, behavioral, hormonal, neuro-vegetative and neural responses) are reviewed in BPD patients. Pathophysiological hypotheses are formulated to explain the differences in responses between BPD patients and healthy subjects and their relation to BPD symptoms. Although the pathogenesis remains uncertain, our conclusions seem to reflect a specific biological and neural pattern of altered stress perception and regulation in BPD. PMID:29250007

The genetic component of human longevity

DEFF Research Database (Denmark)

Dato, Serena; Thinggaard, Mette Sørensen; De Rango, Francesco

2018-01-01

In human longevity studies, single nucleotide polymorphism (SNP) analysis identified a large number of genetic variants with small effects, yet not easily replicable in different populations. New insights may come from the combined analysis of different SNPs, especially when grouped by metabolic...... pathway. We applied this approach to study the joint effect on longevity of SNPs belonging to three candidate pathways, the insulin/insulin-like growth factor signalling (IIS), DNA repair and pro/antioxidant. We analysed data from 1,058 tagging SNPs in 140 genes, collected in 1825 subjects (1......, was further found influencing longitudinal survival in nonagenarian females (p = .026). Results here presented highlight the validity of SNP-SNP interactions analyses for investigating the genetics of human longevity, confirming previously identified markers but also pointing to novel genes as central nodes...

The significance of translation regulation in the stress response

Science.gov (United States)

2013-01-01

Background The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation. Results A genome-scale study of the translational response to nutritional limitation was performed in the model bacterium Lactococcus lactis. Two measures were used to assess the translational status of each individual mRNA: the fraction engaged in translation (ribosome occupancy) and ribosome density (number of ribosomes per 100 nucleotides). Under isoleucine starvation, half of the mRNAs considered were translationally down-regulated mainly due to decreased ribosome density. This pattern concerned genes involved in growth-related functions such as translation, transcription, and the metabolism of fatty acids, phospholipids and bases, contributing to the slowdown of growth. Only 4% of the mRNAs were translationally up-regulated, mostly related to prophagic expression in response to stress. The remaining genes exhibited antagonistic regulations of the two markers of translation. Ribosome occupancy increased significantly for all the genes involved in the biosynthesis of isoleucine, although their ribosome density had decreased. The results revealed complex translational regulation of this pathway, essential to cope with isoleucine starvation. To elucidate the regulation of global gene expression more generally, translational regulation was compared to transcriptional regulation under isoleucine starvation and to other post-transcriptional regulations related to mRNA degradation and mRNA dilution by growth. Translational regulation appeared to accentuate the effects of transcriptional changes for down-regulated growth-related functions under isoleucine starvation although m

The effect of growth regulators on post-harvest Alchemilla mollis (Bauser Rothm. leaf longevity

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Janowska Beata

2016-12-01

Full Text Available Leaves of Alchemilla mollis (Bauser Rothm. were the subject of the study. The leaves were harvested early in the morning from the department’s ornamental plant collection. Selected leaves were fully-developed and showed no signs of damage or discolouring. Gibberellic acid (GA3, benzyladenine (BA, meta-methoxytopolin (MemT and its riboside (MemTR at concentrations of 25, 50 and 75 mg dm−3 were applied in the form of solutions to four-hour leaf-conditioning in the room at a temperature of 18-20°C. After conditioning, the leaves were placed in distilled water. Leaves put into distilled water immediately after cutting served as the control. The post-harvest longevity of leaves of Alchemilla mollis was 7.2-11.8 days. The conditioning of leaves in gibberellic acid solutions at concentrations of 25-50 mg dm−3, benzyladenine at concentrations of 25 mg dm−3 and meta-methoxytopolin and its riboside at concentrations of 75 mg dm−3 extended the post-harvest longevity of leaves by 10.1-81.9%. The conditioning of leaves in gibberellic acid at a concentration of 50 mg dm−3 inhibited the degradation of chlorophyll, as indicated by the highest SPAD index values.

Regulating Anger under Stress via Cognitive Reappraisal and Sadness.

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Zhan, Jun; Wu, Xiaofei; Fan, Jin; Guo, Jianyou; Zhou, Jianshe; Ren, Jun; Liu, Chang; Luo, Jing

2017-01-01

Previous studies have reported the failure of cognitive emotion regulation (CER), especially in regulating unpleasant emotions under stress. The underlying reason for this failure was the application of CER depends heavily on the executive function of the prefrontal cortex (PFC), but this function can be impaired by stress-related neuroendocrine hormones. This observation highlights the necessity of developing self-regulatory strategies that require less top-down cognitive control. Based on traditional Chinese philosophy and medicine, which examine how different types of emotions promote or counteract one another, we have developed a novel emotion regulation strategy whereby one emotion is used to alter another. For example, our previous experiment showed that sadness induction (after watching a sad film) could reduce aggressive behavior associated with anger [i.e., "sadness counteracts anger" (SCA)] (Zhan et al., 2015). Relative to the CER strategy requiring someone to think about certain cognitive reappraisals to reinterpret the meaning of an unpleasant situation, watching a film or listening to music and experiencing the emotion contained therein seemingly requires less cognitive effort and control; therefore, this SCA strategy may be an alternative strategy that compensates for the limitations of cognitive regulation strategies, especially in stressful situations. The present study was designed to directly compare the effects of the CER and SCA strategy in regulating anger and anger-related aggression in stressful and non-stressful conditions. Participants' subjective feeling of anger, anger-related aggressive behavior, skin conductance, and salivary cortisol and alpha-amylase levels were measured. Our findings revealed that acute stress impaired one's ability to use CR to control angry responses provoked by others, whereas stress did not influence the efficiency of the SCA strategy. Compared with sadness or neutral emotion induction, CER induction was found to

Regulating Anger under Stress via Cognitive Reappraisal and Sadness

Directory of Open Access Journals (Sweden)

Jun Zhan

2017-08-01

Full Text Available Previous studies have reported the failure of cognitive emotion regulation (CER, especially in regulating unpleasant emotions under stress. The underlying reason for this failure was the application of CER depends heavily on the executive function of the prefrontal cortex (PFC, but this function can be impaired by stress-related neuroendocrine hormones. This observation highlights the necessity of developing self-regulatory strategies that require less top-down cognitive control. Based on traditional Chinese philosophy and medicine, which examine how different types of emotions promote or counteract one another, we have developed a novel emotion regulation strategy whereby one emotion is used to alter another. For example, our previous experiment showed that sadness induction (after watching a sad film could reduce aggressive behavior associated with anger [i.e., “sadness counteracts anger” (SCA] (Zhan et al., 2015. Relative to the CER strategy requiring someone to think about certain cognitive reappraisals to reinterpret the meaning of an unpleasant situation, watching a film or listening to music and experiencing the emotion contained therein seemingly requires less cognitive effort and control; therefore, this SCA strategy may be an alternative strategy that compensates for the limitations of cognitive regulation strategies, especially in stressful situations. The present study was designed to directly compare the effects of the CER and SCA strategy in regulating anger and anger-related aggression in stressful and non-stressful conditions. Participants’ subjective feeling of anger, anger-related aggressive behavior, skin conductance, and salivary cortisol and alpha-amylase levels were measured. Our findings revealed that acute stress impaired one’s ability to use CR to control angry responses provoked by others, whereas stress did not influence the efficiency of the SCA strategy. Compared with sadness or neutral emotion induction, CER

When stress predicts a shrinking gene pool, trading early reproduction for longevity can increase fitness, even with lower fecundity.

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William C Ratcliff

2009-06-01

Full Text Available Stresses like dietary restriction or various toxins increase lifespan in taxa as diverse as yeast, Caenorhabditis elegans, Drosophila and rats, by triggering physiological responses that also tend to delay reproduction. Food odors can reverse the effects of dietary restriction, showing that key mechanisms respond to information, not just resources. Such environmental cues can predict population trends, not just individual prospects for survival and reproduction. When population size is increasing, each offspring produced earlier makes a larger proportional contribution to the gene pool, but the reverse is true when population size is declining.We show mathematically that natural selection can favor facultative delay in reproduction when environmental cues predict a decrease in total population size, even if lifetime fecundity decreases with delay. We also show that increased reproduction from waiting for better conditions does not increase fitness (proportional representation when the whole population benefits similarly.We conclude that the beneficial effects of stress on longevity (hormesis in diverse taxa are a side-effect of delaying reproduction in response to environmental cues that population size is likely to decrease. The reversal by food odors of the effects of dietary restriction can be explained as a response to information that population size is less likely to decrease, reducing the chance that delaying reproduction will increase fitness.

Plant Responses to Abiotic Stress Regulated by Histone Deacetylases

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Ming Luo

2017-12-01

Full Text Available In eukaryotic cells, histone acetylation and deacetylation play an important role in the regulation of gene expression. Histone acetylation levels are modulated by histone acetyltransferases and histone deacetylases (HDACs. Recent studies indicate that HDACs play essential roles in the regulation of gene expression in plant response to environmental stress. In this review, we discussed the recent advance regarding the plant HDACs and their functions in the regulation of abiotic stress responses. The role of HDACs in autophagy was also discussed.

Reactive oxygen species, health and longevity

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Vittorio Emanuele Bianchi

2016-09-01

Full Text Available Reactive oxygen species (ROS are considered responsible of ageing in animal and humans. Mitochondria are both source and target of ROS. Various strategies to reduce ROS production have been considered to extend lifespan. Caloric restriction, exercise, and antioxidants are thought to be able to protect cells from structural and functional damage. However, there is evidence that ROS production has a detrimental effect on health, but at physiological levels are necessary to stimulate longevity. They play an important effect on secondary signal transduction stimulating innate immunology and mitochondriogenesis. During exercise at moderate intensity, skeletal muscles generate ROS that are necessary for the remodelling of the muscular cells. Physical inactivity determines excessive ROS production and muscle atrophy. Caloric restriction (CR can reduce ROS generation and improve longevity while antioxidant supplementation has shown a negative effect on longevity reducing the muscle adaptation to exercise and increasing mortality risk in patients with chronic diseases. The role of ROS in chronic diseases in also influenced by sex steroids that decrease in aging. The physiology of longevity is the result of integrated biological mechanisms that influence mitochondrial function and activity. The main objective of this review is to evaluate the effects of ROS on mitochondriogenesis and lifespan extension.

Dynamic O-GlcNAc cycling at promoters of Caenorhabditis elegans genes regulating longevity, stress, and immunity.

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Love, Dona C; Ghosh, Salil; Mondoux, Michelle A; Fukushige, Tetsunari; Wang, Peng; Wilson, Mark A; Iser, Wendy B; Wolkow, Catherine A; Krause, Michael W; Hanover, John A

2010-04-20

Nutrient-driven O-GlcNAcylation of key components of the transcription machinery may epigenetically modulate gene expression in metazoans. The global effects of GlcNAcylation on transcription can be addressed directly in C. elegans because knockouts of the O-GlcNAc cycling enzymes are viable and fertile. Using anti-O-GlcNAc ChIP-on-chip whole-genome tiling arrays on wild-type and mutant strains, we detected over 800 promoters where O-GlcNAc cycling occurs, including microRNA loci and multigene operons. Intriguingly, O-GlcNAc-marked promoters are biased toward genes associated with PIP3 signaling, hexosamine biosynthesis, and lipid/carbohydrate metabolism. These marked genes are linked to insulin-like signaling, metabolism, aging, stress, and pathogen-response pathways in C. elegans. Whole-genome transcriptional profiling of the O-GlcNAc cycling mutants confirmed dramatic deregulation of genes in these key pathways. As predicted, the O-GlcNAc cycling mutants show altered lifespan and UV stress susceptibility phenotypes. We propose that O-GlcNAc cycling at promoters participates in a molecular program impacting nutrient-responsive pathways in C. elegans, including stress, pathogen response, and adult lifespan. The observed impact of O-GlcNAc cycling on both signaling and transcription in C. elegans has important implications for human diseases of aging, including diabetes and neurodegeneration.

DAF-2/insulin-like signaling in C. elegans modifies effects of dietary restriction and nutrient stress on aging, stress and growth.

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Wendy B Iser

2007-11-01

Full Text Available Dietary restriction (DR and reduced insulin/IGF-I-like signaling (IIS are two regimens that promote longevity in a variety of organisms. Genetic analysis in C. elegans nematodes has shown that DR and IIS couple to distinct cellular signaling pathways. However, it is not known whether these pathways ultimately converge on overlapping or distinct targets to extend lifespan.We investigated this question by examining additional effects of DR in wildtype animals and in daf-2 mutants with either moderate or severe IIS deficits. Surprisingly, DR and IIS had opposing effects on these physiological processes. First, DR induced a stress-related change in intestinal vesicle trafficking, termed the FIRE response, which was suppressed in daf-2 mutants. Second, DR did not strongly affect expression of a daf-2- and stress-responsive transcriptional reporter. Finally, DR-related growth impairment was suppressed in daf-2 mutants.These findings reveal that an important biological function of DAF-2/IIS is to enhance growth and survival under nutrient-limited conditions. However, we also discovered that levels of DAF-2 pathway activity modified the effects of DR on longevity. Thus, while DR and IIS clearly affect lifespan through independent targets, there may also be some prolongevity targets that are convergently regulated by these pathways.

DAF-2/insulin-like signaling in C. elegans modifies effects of dietary restriction and nutrient stress on aging, stress and growth.

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Iser, Wendy B; Wolkow, Catherine A

2007-11-28

Dietary restriction (DR) and reduced insulin/IGF-I-like signaling (IIS) are two regimens that promote longevity in a variety of organisms. Genetic analysis in C. elegans nematodes has shown that DR and IIS couple to distinct cellular signaling pathways. However, it is not known whether these pathways ultimately converge on overlapping or distinct targets to extend lifespan. We investigated this question by examining additional effects of DR in wildtype animals and in daf-2 mutants with either moderate or severe IIS deficits. Surprisingly, DR and IIS had opposing effects on these physiological processes. First, DR induced a stress-related change in intestinal vesicle trafficking, termed the FIRE response, which was suppressed in daf-2 mutants. Second, DR did not strongly affect expression of a daf-2- and stress-responsive transcriptional reporter. Finally, DR-related growth impairment was suppressed in daf-2 mutants. These findings reveal that an important biological function of DAF-2/IIS is to enhance growth and survival under nutrient-limited conditions. However, we also discovered that levels of DAF-2 pathway activity modified the effects of DR on longevity. Thus, while DR and IIS clearly affect lifespan through independent targets, there may also be some prolongevity targets that are convergently regulated by these pathways.

ENVIRONMENTAL MECHANISM OF REGIONAL LONGEVITY IN CHINA

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Wuyi Wang

2015-01-01

Full Text Available The integrated study on environment of typical China’s longevity areas was conducted by using comprehensive methods of health geography. It was found that Chinese longevity areas mainly located in the south China and clustered in Sichuan-Chongqing, Central plain and Southeast region, the Yangtze River Delta and Pearl River Delta; in which drinking water was of weakly alkaline, Se, Fe, K content was moderate, higher content of Ca, Co, Mn, and low Cr, Cd, Pb; the concentration of trace elements benefit for health in soils and food staples was higher; hair of centenarians had higher Li, Mg, Mn, Ca, Zn content, lower concentration in Cd, Cr, Cu, Ni; healthy centenarians were also benefited from a favorable social environment factors, such as physiological health, psychological state, light meals and higher proportion of vegetables. The study was the first time to reveal quantitatively the relationship between longevity and the natural and human environment, and provided a scientific basis for the promotion of development of China’s longevity area, to achieve the construction of ecological civilization

Protein stress and stress proteins: implications in aging and disease

Indian Academy of Sciences (India)

Madhu Sudhan

2007-04-02

Apr 2, 2007 ... (iii) modulating protein activity via stabilization and/or maturation to ... Resistance to any physical stress is correlated with longevity in many, if not all .... range of pathologies including cancer, diabetes, immune- problems and ...

Germline signaling mediates the synergistically prolonged longevity produced by double mutations in daf-2 and rsks-1 in C. elegans.

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Chen, Di; Li, Patrick Wai-Lun; Goldstein, Benjamin A; Cai, Waijiao; Thomas, Emma Lynn; Chen, Fen; Hubbard, Alan E; Melov, Simon; Kapahi, Pankaj

2013-12-26

Inhibition of DAF-2 (insulin-like growth factor 1 [IGF-1] receptor) or RSKS-1 (S6K), key molecules in the insulin/IGF-1 signaling (IIS) and target of rapamycin (TOR) pathways, respectively, extend lifespan in Caenorhabditis elegans. However, it has not been clear how and in which tissues they interact with each other to modulate longevity. Here, we demonstrate that a combination of mutations in daf-2 and rsks-1 produces a nearly 5-fold increase in longevity that is much greater than the sum of single mutations. This synergistic lifespan extension requires positive feedback regulation of DAF-16 (FOXO) via the AMP-activated protein kinase (AMPK) complex. Furthermore, we identify germline as the key tissue for this synergistic longevity. Moreover, germline-specific inhibition of rsks-1 activates DAF-16 in the intestine. Together, our findings highlight the importance of the germline in the significantly increased longevity produced by daf-2 rsks-1, which has important implications for interactions between the two major conserved longevity pathways in more complex organisms. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Endoplasmic reticulum stress pathway required for immune homeostasis is neurally controlled by arrestin-1.

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Singh, Varsha; Aballay, Alejandro

2012-09-28

In response to pathogen infection, the host innate immune system activates microbial killing pathways and cellular stress pathways that need to be balanced because insufficient or excessive immune responses have deleterious consequences. Recent studies demonstrate that two G protein-coupled receptors (GPCRs) in the nervous system of Caenorhabditis elegans control immune homeostasis. To investigate further how GPCR signaling controls immune homeostasis at the organismal level, we studied arrestin-1 (ARR-1), which is the only GPCR adaptor protein in C. elegans. The results indicate that ARR-1 is required for GPCR signaling in ASH, ASI, AQR, PQR, and URX neurons, which control the unfolded protein response and a p38 mitogen-activated protein kinase signaling pathway required for innate immunity. ARR-1 activity also controlled immunity through ADF chemosensory and AFD thermosensory neurons that regulate longevity. Furthermore, we found that although ARR-1 played a key role in the control of immunity by AFD thermosensory neurons, it did not control longevity through these cells. However, ARR-1 partially controlled longevity through ADF neurons.

Longevity, Growth and Intergenerational Equity: The Deterministic Case

DEFF Research Database (Denmark)

Andersen, Torben M.; Gestsson, Marias Halldór

2016-01-01

develop an overlapping-generations model in continuous time that encompasses different generations with different mortality rates and thus longevity. Allowing for trend increases in both longevity and productivity, we address the normative issue of intergenerational equity under a utilitarian criterion...

Longevity, Growth and Intergenerational Equity - The Deterministic Case

DEFF Research Database (Denmark)

Andersen, Torben M.; Gestsson, Marias Halldór

. We develop an overlapping generations model in continuous time which encompasses different generations with different mortality rates and thus longevity. Allowing for both trend increases in longevity and productivity, we address the issue of intergenerational equity under a utilitarian criterion...

Handgrip strength at midlife and familial longevity : The Leiden Longevity Study

NARCIS (Netherlands)

Ling, Carolina H.Y.; De Craen, Anton J.M.; Eline Slagboom, P.; Westendorp, Rudi G.J.; Maier, Andrea B.

2012-01-01

Low handgrip strength has been linked with premature mortality in diverse samples of middle-aged and elderly subjects. The value of handgrip strength as marker of "exceptional" human longevity has not been previously explored. We postulated that the genetic influence on extreme survival might also

Regulation of Translation Initiation under Biotic and Abiotic Stresses

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Ana B. Castro-Sanz

2013-02-01

Full Text Available Plants have developed versatile strategies to deal with the great variety of challenging conditions they are exposed to. Among them, the regulation of translation is a common target to finely modulate gene expression both under biotic and abiotic stress situations. Upon environmental challenges, translation is regulated to reduce the consumption of energy and to selectively synthesize proteins involved in the proper establishment of the tolerance response. In the case of viral infections, the situation is more complex, as viruses have evolved unconventional mechanisms to regulate translation in order to ensure the production of the viral encoded proteins using the plant machinery. Although the final purpose is different, in some cases, both plants and viruses share common mechanisms to modulate translation. In others, the mechanisms leading to the control of translation are viral- or stress-specific. In this paper, we review the different mechanisms involved in the regulation of translation initiation under virus infection and under environmental stress in plants. In addition, we describe the main features within the viral RNAs and the cellular mRNAs that promote their selective translation in plants undergoing biotic and abiotic stress situations.

"Real life" longevity of implantable cardioverter-defibrillator devices.

Science.gov (United States)

Manolis, Antonis S; Maounis, Themistoklis; Koulouris, Spyridon; Vassilikos, Vassilios

2017-09-01

Manufacturers of implantable cardioverter-defibrillators (ICDs) promise a 5- to 9-year projected longevity; however, real-life data indicate otherwise. The aim of the present study was to assess ICD longevity among 685 consecutive patients over the last 20 years. Real-life longevity of ICDs may differ from that stated by the manufacturers. The study included 601 men and 84 women (mean age, 63.1 ± 13.3 years). The underlying disease was coronary (n = 396) or valvular (n = 15) disease, cardiomyopathy (n = 220), or electrical disease (n = 54). The mean ejection fraction was 35%. Devices were implanted for secondary (n = 562) or primary (n = 123) prevention. Single- (n = 292) or dual-chamber (n = 269) or cardiac resynchronization therapy (CRT) devices (n = 124) were implanted in the abdomen (n = 17) or chest (n = 668). Over 20 years, ICD pulse generator replacements were performed in 238 patients (209 men; age 63.7 ± 13.9 years; ejection fraction, 37.7% ± 14.0%) who had an ICD for secondary (n = 210) or primary (n = 28) prevention. The mean ICD longevity was 58.3 ± 18.7 months. In 20 (8.4%) patients, devices exhibited premature battery depletion within 36 months. Most (94%) patients had none, minor, or modest use of ICD therapy. Longevity was longest for single-chamber devices and shortest for CRT devices. Latest-generation devices replaced over the second decade lasted longer compared with devices replaced during the first decade. When analyzed by manufacturer, Medtronic devices appeared to have longer longevity by 13 to 18 months. ICDs continue to have limited longevity of 4.9 ± 1.6 years, and 8% demonstrate premature battery depletion by 3 years. CRT devices have the shortest longevity (mean, 3.8 years) by 13 to 17 months, compared with other ICD devices. These findings have important implications, particularly in view of the high expense involved with this type of electrical

Power Estimation for Gene-Longevity Association Analysis Using Concordant Twins

DEFF Research Database (Denmark)

Tan, Qihua; Zhao, Jing Hua; Kruse, Torben A

2014-01-01

Statistical power is one of the major concerns in genetic association studies. Related individuals such as twins are valuable samples for genetic studies because of their genetic relatedness. Phenotype similarity in twin pairs provides evidence of genetic control over the phenotype variation...... in a population. The genetic association study on human longevity, a complex trait that is under control of both genetic and environmental factors, has been confronted by the small sample sizes of longevity subjects which limit statistical power. Twin pairs concordant for longevity have increased probability...... an approximate of 2- to 3-fold increase in sample sizes needed for longevity cutoff at age 90 as compared with that at age 95. Overall, our results showed high value of twins in genetic association studies on human longevity....

Longevity of dental amalgam in comparison to composite materials

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Windisch, Friederike

2008-11-01

Full Text Available Health political background: Caries is one of the most prevalent diseases worldwide. For (direct restaurations of carious lesions, tooth-coloured composite materials are increasingly used. The compulsory health insurance pays for composite fillings in front teeth; in posterior teeth, patients have to bear the extra cost. Scientific background: Amalgam is an alloy of mercury and other metals and has been used in dentistry for more than one hundred and fifty years. Composites consist of a resin matrix and chemically bonded fillers. They have been used for about fifty years in front teeth. Amalgam has a long longevity; the further development of composites has also shown improvements regarding their longevity. Research questions: This HTA-report aims to evaluate the longevity (failure rate, median survival time (MST, median age of direct amalgam fillings in comparison to direct composite fillings in permanent teeth from a medical and economical perspective and discusses the ethical, legal and social aspects of using these filling materials. Methods: The systematic literature search yielded a total of 1,149 abstracts. After a two-step selection process based on defined criteria 25 publications remained to be assessed. Results: The medical studies report a longer longevity for amalgam fillings than for composite fillings. However, the results of these studies show a large heterogeneity. No publication on the costs or the cost-effectiveness of amalgam and composite fillings exists for Germany. The economic analyses (NL, SWE, GB report higher costs for composite fillings when longevity is assumed equal (for an observation period of five years or longer for amalgam compared to composite fillings. These higher costs are due to the higher complexity of placing composite fillings. Discussion: Due to different study designs and insufficient documentation of study details, a comparison of different studies on longevity of direct amalgam and composite

Novel loci and pathways significantly associated with longevity

DEFF Research Database (Denmark)

Zeng, Yi; Nie, Chao; Min, Junxia

2016-01-01

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han ...

Cancer and Longevity--Is There a Trade-off?

DEFF Research Database (Denmark)

Christensen, Kaare; Pedersen, Jacob K; Hjelmborg, Jacob V B

2012-01-01

Animal models and a few human studies have suggested a complex interaction between cancer risk and longevity indicating a trade-off where low cancer risk is associated with accelerating aging phenotypes and, vice versa, that longevity potential comes with the cost of increased cancer risk...

Longevity and mortality of owned dogs in England.

Science.gov (United States)

O'Neill, D G; Church, D B; McGreevy, P D; Thomson, P C; Brodbelt, D C

2013-12-01

Improved understanding of longevity represents a significant welfare opportunity for the domestic dog, given its unparalleled morphological diversity. Epidemiological research using electronic patient records (EPRs) collected from primary veterinary practices overcomes many inherent limitations of referral clinic, owner questionnaire and pet insurance data. Clinical health data from 102,609 owned dogs attending first opinion veterinary practices (n=86) in central and southeast England were analysed, focusing on 5095 confirmed deaths. Of deceased dogs with information available, 3961 (77.9%) were purebred, 2386 (47.0%) were female, 2528 (49.8%) were neutered and 1105 (21.7%) were insured. The overall median longevity was 12.0 years (IQR 8.9-14.2). The longest-lived breeds were the Miniature poodle, Bearded collie, Border collie and Miniature dachshund, while the shortest-lived were the Dogue de Bordeaux and Great Dane. The most frequently attributed causes of death were neoplastic, musculoskeletal and neurological disorders. The results of multivariable modelling indicated that longevity in crossbred dogs exceeded purebred dogs by 1.2 years (95% confidence interval 0.9-1.4; P<0.001) and that increasing bodyweight was negatively correlated with longevity. The current findings highlight major breed differences for longevity and support the concept of hybrid vigour in dogs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Longevity risks and capital markets: The 2010-2011 update

OpenAIRE

Blake, David; Courbage, Christophe; MacMinn, Richard; Sherris, Michael

2011-01-01

This Special Issue of Geneva Papers on Risk and Insurance - Issues and Practice contains 10 contributions to the academic literature all dealing with longevity risk and capital markets. Draft versions of the papers were presented at Longevity Six: The Sixth International Longevity Risk and Capital Markets Solutions Conference that was held in Sydney on 9-10 September 2010. It was hosted by the Australian Institute for Population Ageing Research, the Australian School of Business and the Unive...

Mental stress: Neurophysiology and its regulation by Sudarshan Kriya Yoga

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Sushil Chandra

2017-01-01

Full Text Available Aim: The present study focuses on analyzing the effects of Sudarshan Kriya yoga (SKY on EEG as well as ECG signals for stress regulation. To envision the regulation of stress Determination Test (DT has been used. We have chosen a control group for contriving a cogent comparison that could be corroborated using statistical tests. Subjects and Methods: A total of 20 subjects were taken in the study, of which 10 were allotted to a control group. Electroencephalograph was taken during a DT task, before and after SKY the sky session with 30 days of SKY session given to the experimental group. No SKY was given to the control group. Results: We quantified mental stress using EEG, ECG and DT synergistically and used SKY to regulate it. We observed that alpha band power decreases in the frontal lobe of the brain with increasing mental stress while frontal brain asymmetry decreases with increasing stress tolerance. Conclusions: These EEG, ECG and DT shows a significant decrement in mental stress and improvement in cognitive performance after SKY, indicating SKY as a good alternative of medication for stress management.

Effects of anger regulation and social anxiety on perceived stress

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Ayano Yamaguchi

2015-08-01

Full Text Available The mediating role of social anxiety was explored within the effect of anger regulation on perceived stress in the national sample of American and Japanese older adults. Results indicated that anger suppression is a significant factor in perceived stress mediated by social anxiety. Anger suppression was also directly related to perceived stress. The correlation of anger suppression with social anxiety was stronger in Japan than in the United States. Understanding both universal and culture-specific aspects of emotion regulation and perceived stress will be essential for the development of sound theory, future research, and effective prevention and intervention efforts.

Specific microRNAs Regulate Heat Stress Responses in Caenorhabditis elegans

DEFF Research Database (Denmark)

Nehammer, Camilla; Podolska, Agnieszka; Mackowiak, Sebastian D

2015-01-01

have identified additional functions for already known players (mir-71 and mir-239) as well as identifying mir-80 and the mir-229 mir-64-66 cluster as important regulators of the heat stress response in C. elegans. These findings uncover an additional layer of complexity to the regulation of stress...... to heat stress in Caenorhabditis elegans and show that a discrete subset of miRNAs is thermoregulated. Using in-depth phenotypic analyses of miRNA deletion mutant strains we reveal multiple developmental and post-developmental survival and behavioral functions for specific miRNAs during heat stress. We...

Regulation of cellulose synthesis in response to stress.

Science.gov (United States)

Kesten, Christopher; Menna, Alexandra; Sánchez-Rodríguez, Clara

2017-12-01

The cell wall is a complex polysaccharide network that provides stability and protection to the plant and is one of the first layers of biotic and abiotic stimuli perception. A controlled remodeling of the primary cell wall is essential for the plant to adapt its growth to environmental stresses. Cellulose, the main component of plant cell walls is synthesized by plasma membrane-localized cellulose synthases moving along cortical microtubule tracks. Recent advancements demonstrate a tight regulation of cellulose synthesis at the primary cell wall by phytohormone networks. Stress-induced perturbations at the cell wall that modify cellulose synthesis and microtubule arrangement activate similar phytohormone-based stress response pathways. The integration of stress perception at the primary cell wall and downstream responses are likely to be tightly regulated by phytohormone signaling pathways in the context of cellulose synthesis and microtubule arrangement. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Protein kinase FgSch9 serves as a mediator of the target of rapamycin and high osmolarity glycerol pathways and regulates multiple stress responses and secondary metabolism in Fusarium graminearum.

Science.gov (United States)

Gu, Qin; Zhang, Chengqi; Yu, Fangwei; Yin, Yanni; Shim, Won-Bo; Ma, Zhonghua

2015-08-01

Saccharomyces cerevisiae protein kinase Sch9 is one of the downstream effectors of the target of rapamycin (TOR) complex 1 and plays multiple roles in stress resistance, longevity and nutrient sensing. However, the functions of Sch9 orthologs in filamentous fungi, particularly in pathogenic species, have not been characterized to date. Here, we investigated biological and genetic functions of FgSch9 in Fusarium graminearum. The FgSCH9 deletion mutant (ΔFgSch9) was defective in aerial hyphal growth, hyphal branching and conidial germination. The mutant exhibited increased sensitivity to osmotic and oxidative stresses, cell wall-damaging agents, and to rapamycin, while showing increased thermal tolerance. We identified FgMaf1 as one of the FgSch9-interacting proteins that plays an important role in regulating mycotoxin biosynthesis and virulence of F. graminearum. Co-immunoprecipitation and affinity capture-mass spectrometry assays showed that FgSch9 also interacts with FgTor and FgHog1. More importantly, both ΔFgSch9 and FgHog1 null mutant (ΔFgHog1) exhibited increased sensitivity to osmotic and oxidative stresses. This defect was more severe in the FgSch9/FgHog1 double mutant. Taken together, we propose that FgSch9 serves as a mediator of the TOR and high osmolarity glycerol pathways, and regulates vegetative differentiation, multiple stress responses and secondary metabolism in F. graminearum. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

Activation of DAF-16/FOXO by reactive oxygen species contributes to longevity in long-lived mitochondrial mutants in Caenorhabditis elegans.

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Senchuk, Megan M; Dues, Dylan J; Schaar, Claire E; Johnson, Benjamin K; Madaj, Zachary B; Bowman, Megan J; Winn, Mary E; Van Raamsdonk, Jeremy M

2018-03-01

Mild deficits in mitochondrial function have been shown to increase lifespan in multiple species including worms, flies and mice. Here, we study three C. elegans mitochondrial mutants (clk-1, isp-1 and nuo-6) to identify overlapping genetic pathways that contribute to their longevity. We find that genes regulated by the FOXO transcription factor DAF-16 are upregulated in all three strains, and that the transcriptional changes present in these worms overlap significantly with the long-lived insulin-IGF1 signaling pathway mutant daf-2. We show that DAF-16 and multiple DAF-16 interacting proteins (MATH-33, IMB-2, CST-1/2, BAR-1) are required for the full longevity of all three mitochondrial mutants. Our results suggest that the activation of DAF-16 in these mutants results from elevated levels of reactive oxygen species. Overall, this work reveals an overlapping genetic pathway required for longevity in three mitochondrial mutants, and, combined with previous work, demonstrates that DAF-16 is a downstream mediator of lifespan extension in multiple pathways of longevity.

Stressful gaming, interoceptive awareness, and emotion regulation tendencies: A novel approach

NARCIS (Netherlands)

Lobel, A.M.; Granic, I.; Engels, R.C.M.E.

2014-01-01

Healthy emotion regulation is crucial for navigating stressful situations. Interoceptive awareness-the awareness of one's internal states-is important for such healthy regulation. Given the propensity for video games to induce stress, the associations between in-game and real world emotion

The Yeast Environmental Stress Response Regulates Mutagenesis Induced by Proteotoxic Stress

Science.gov (United States)

Shor, Erika; Fox, Catherine A.; Broach, James R.

2013-01-01

Conditions of chronic stress are associated with genetic instability in many organisms, but the roles of stress responses in mutagenesis have so far been elucidated only in bacteria. Here, we present data demonstrating that the environmental stress response (ESR) in yeast functions in mutagenesis induced by proteotoxic stress. We show that the drug canavanine causes proteotoxic stress, activates the ESR, and induces mutagenesis at several loci in an ESR-dependent manner. Canavanine-induced mutagenesis also involves translesion DNA polymerases Rev1 and Polζ and non-homologous end joining factor Ku. Furthermore, under conditions of chronic sub-lethal canavanine stress, deletions of Rev1, Polζ, and Ku-encoding genes exhibit genetic interactions with ESR mutants indicative of ESR regulating these mutagenic DNA repair processes. Analyses of mutagenesis induced by several different stresses showed that the ESR specifically modulates mutagenesis induced by proteotoxic stress. Together, these results document the first known example of an involvement of a eukaryotic stress response pathway in mutagenesis and have important implications for mechanisms of evolution, carcinogenesis, and emergence of drug-resistant pathogens and chemotherapy-resistant tumors. PMID:23935537

Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans, and replicative lifespan in yeast

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Srinivas eAyyadevara

2014-08-01

Full Text Available A quantitative trait locus (QTL in the nematode C. elegans, lsq4, was recently implicated by mapping longevity genes. QTLs for lifespan and 3 stress-resistance traits coincided within a span of <300 kbp, later narrowed to <200 kbp. A single gene in this interval is now shown to modulate all lsq4-associated traits. Full-genome analysis of transcript levels indicates that lsq4 contains a dimorphic gene governing expression of sperm-specific genes, suggesting effects on spermatogenesis. Quantitation of allele-specific transcripts encoded within the lsq4 interval revealed significant, 2- to 15-fold expression differences for 10 of 33 genes. Fourteen genes, implicated by both position and expression, were tested for RNA-interference effects on QTL-linked traits. In a strain carrying the shorter-lived allele, knockdown of rec-8 (encoding a meiotic cohesin reduced its transcripts 4-fold, to a level similar to the longer-lived strain, and extended lifespan 25–26% whether begun before fertilization or at maturity. The short-lived lsq4 allele also conferred sensitivity to oxidative and thermal stresses, and lower male frequency, traits reversed uniquely by rec-8 knockdown. A strain bearing the longer-lived lsq4 allele, differing from the short-lived strain at <0.3% of its genome, derived no lifespan or stress-survival benefit from rec-8 knockdown. We consider two possible explanations: high rec-8 expression may include increased leaky expression in mitotic cells, leading to deleterious destabilization of somatic genomes; or REC-8 may act entirely in germ-line meiotic cells to reduce aberrations such as nondisjunction, thereby blunting a stress-resistance response mediated by innate immunity. Replicative lifespan was extended 20% in haploid S. cerevisiae (BY4741 by deletion of REC8, orthologous to nematode rec-8, implying that REC8 disruption of mitotic-cell survival is widespread, reflecting antagonistic pleiotropy and/or balancing selection.

MATERNAL TRAUMA AFFECTS PRENATAL MENTAL HEALTH AND INFANT STRESS REGULATION AMONG PALESTINIAN DYADS.

Science.gov (United States)

Isosävi, Sanna; Diab, Safwat Y; Kangaslampi, Samuli; Qouta, Samir; Kankaanpää, Saija; Puura, Kaija; Punamäki, Raija-Leena

2017-09-01

We examined how diverse and cumulated traumatic experiences predicted maternal prenatal mental health and infant stress regulation in war conditions and whether maternal mental health mediated the association between trauma and infant stress regulation. Participants were 511 Palestinian mothers from the Gaza Strip who reported exposure to current war trauma (WT), past childhood emotional (CEA) and physical abuse, socioeconomic status (SES), prenatal mental health problems (posttraumatic stress disorder and depression symptoms), and perceived stress during their secondtrimester of pregnancy as well as infant stress regulation at 4 months. While all trauma types were associated with high levels of prenatal symptoms, CEA had the most wide-ranging effects and was uniquely associated with depression symptoms. Concerning infant stress regulation, mothers' CEA predicted negative affectivity, but only among mothers with low WT. Against hypothesis, the effects of maternal trauma on infant stress regulation were not mediated by mental health symptoms. Mothers' higher SES was associated with better infant stress regulation whereas infant prematurity and male sex predisposed for difficulties. Our findings suggest that maternal childhood abuse, especially CEA, should be a central treatment target among war-exposed families. Cumulated psychosocial stressors might increase the risk for transgenerational problems. © 2017 Michigan Association for Infant Mental Health.

Posttraumatic stress, difficulties in emotion regulation, and coping-oriented marijuana use.

Science.gov (United States)

Bonn-Miller, Marcel O; Vujanovic, Anka A; Boden, Matthew Tyler; Gross, James J

2011-01-01

In an effort to better understand factors that may explain prior findings of a positive relation between posttraumatic stress symptom severity and coping-oriented marijuana use motivation, the present study tested whether the association between posttraumatic stress symptom severity and marijuana use coping motives is mediated by difficulties in emotion regulation. Participants were 79 (39 women; M(age) = 22.29 years, SD = 6.99) community-recruited adults who reported (1) lifetime exposure to at least one posttraumatic stress disorder Criterion A traumatic event and (2) marijuana use in the past 30 days. Results indicated that difficulties in emotion regulation, as indexed by the Difficulties in Emotion Regulation Scale (Gratz & Roemer, 2004), fully mediated the association between posttraumatic stress symptom severity and marijuana use coping motives. Implications for the treatment of co-occurring posttraumatic stress and marijuana use are discussed.

Lifestyle factors of people with exceptional longevity.

Science.gov (United States)

Rajpathak, Swapnil N; Liu, Yingheng; Ben-David, Orit; Reddy, Saritha; Atzmon, Gil; Crandall, Jill; Barzilai, Nir

2011-08-01

To assess lifestyle factors including physical activity, smoking, alcohol consumption, and dietary habits in men and women with exceptional longevity. Retrospective cohort study. A cohort of community-dwelling Ashkenazi Jewish individuals with exceptional longevity defined as survival and living independently at age 95 and older. Four hundred seventy-seven individuals (mean 97.3 ± 2.8, range 95-109; 74.6% women) and a subset of participants of the National Health and Nutrition Examination Survey (NHANES) I (n = 3,164) representing the same birth cohort as a comparison group. A trained interviewer administrated study questionnaires to collect information on lifestyle factors and collected data on anthropometry. People with exceptional longevity had similar mean body mass index (men, 25.4 ± 2.8 kg/m² vs 25.6 ± 4.0 kg/m² , P=.63; women, 25.0 ± 3.5 kg/m² vs 24.9 ± 5.4 kg/m² ; P = .90) and a similar proportion of daily alcohol consumption (men, 23.9 vs 22.4, P = .77; women, 12.1 vs 11.3, P = .80), of regular physical activity (men: 43.1 vs 57.2; P = .07; women: 47.0 vs 44.1, P = .76), and of a low-calorie diet (men: 20.8 vs 21.1, P=.32; women: 27.3 vs 27.1, P=.14) as the NHANES I population. People with exceptional longevity are not distinct in terms of lifestyle factors from the general population, suggesting that people with exceptional longevity may interact with environmental factors differently than others. This requires further investigation. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

How Do Stress Exposure and Stress Regulation Relate to Borderline Personality Disorder?

OpenAIRE

Bourvis, Nadège; Aouidad, Aveline; Cabelguen, Clémence; Cohen, David; Xavier, Jean

2017-01-01

Borderline personality disorder (BPD) is a severe and frequent disorder characterized by a pervasive pattern of instability affecting impulse control, emotional regulation, cognitive processing, self-image and interpersonal relationships. Patients’ personal histories are often marked by stressful or traumatic experiences, either unique or repeated. Moreover, while clinical signs of the disorder include both chronic and acute features, acute features are mostly triggered by acute stressful sit...

Duration of senescent cell survival in vitro as a characteristic of organism longevity, an additional to the proliferative potential of fibroblasts.

Science.gov (United States)

Yegorov, Yegor E; Zelenin, Alexander V

2003-04-24

More than 40 years have passed since the original publication by Hayflick and Moorhead led to the concept of the 'Hayflick limit' of the maximum number of divisions which somatic cells undergo in vitro. This concept is still regarded as a fundamental characteristic of species longevity. Here we want to emphasize another characteristic of somatic cells, namely, the duration of their survival in vitro in the non-dividing state after cessation of proliferation. This is suggested on the basis of results of recent experiments with so-called Japanese accelerated senescent mice. Results of these experiments reveal a good correlation between the longevity of the mice, the number of duplications of their fibroblasts in vitro, and the survival time of these cells in the non-dividing state. In routine culture conditions, cell survival time may be very long, as much as a few years. However, when the cells are grown under conditions of oxidative stress, cellular longevity is markedly shortened. This new test may serve as an additional marker of organismic longevity. The comparative value of both tests, the classical 'Hayflick limit' and the new test, is discussed.

Ponderosa Pine Forest Restoration Treatment Longevity: Implications of Regeneration on Fire Hazard

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Wade T. Tinkham

2016-07-01

Full Text Available Restoration of pine forests has become a priority for managers who are beginning to embrace ideas of highly heterogeneous forest structures that potentially encourages high levels of regeneration. This study utilizes stem-mapped stands to assess how simulated regeneration timing and magnitude influence longevity of reduced fire behavior by linking growth and yield model outputs to a crown fire prediction model. Treatment longevity was assessed as return time to within 10% of pre-treatment predicted wind speeds for the onset of passive (Torching and active (Crowning crown fire behavior. Treatment longevity in terms of Torching and Crowning was reduced 5 years for every 550 and 150 seedlings ha−1, respectively. Introducing regeneration as a single pulse further reduced Torching treatment longevity 10 years compared to other regeneration distributions. Crowning treatment longevity increased at higher site indices, where a 6 m increase in site index increased longevity 4.5 year. This result was contrary to expectations that canopy openings after treatments would close faster on higher productivity sites. Additionally, Torching longevity was influenced by the rate of crown recession, were reducing the recession rate decreased longevity in areas with higher site indices. These dependencies highlight a need for research exploring stand development in heterogeneous sites.

Early and extraordinary peaks in physical performance come with a longevity cost

DEFF Research Database (Denmark)

van de Vijver, Paul L; van Bodegom, David; Westendorp, Rudi G J

2016-01-01

Life history theory postulates a trade-off between development and maintenance. This trade-off is observed when comparing life histories of different animal species. In humans, however, it is debated if variation in longevity is explained by differences in developmental traits. Observational...... studies found a trade-off between early and high fecundity and longevity in women. Development encompasses more than fecundity and also concerns growth and physical performance. Here, we show a life history trade-off between early and above average physical performance and longevity in male Olympic...... suffered a 4.7-year longevity cost. (95% CI 2.1-7.5 years, p=0.001). This is the first time a life history trade-off between physical performance and longevity has been found in humans. This finding deepens our understanding of early developmental influences on the variation of longevity in humans....

Polyamines Function in Stress Tolerance: From Synthesis to Regulation

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Ji-Hong eLiu

2015-10-01

Full Text Available Plants are challenged by a variety of biotic or abiotic stresses, which can affect their growth and development, productivity and geographic distribution. In order to survive adverse environmental conditions, plants have evolved various adaptive strategies, among which is the accumulation of metabolites that play protective roles. A well-established example of the metabolites that are involved in stress responses, or stress tolerance, is the low-molecular-weight aliphatic polyamines, including putrescine,spermidine and spermine. The critical role of polyamines in stress tolerance is suggested by several lines of evidence: firstly, the transcript levels of polyamine biosynthetic genes, as well as the activities of the corresponding enzymes, are induced by stresses; secondly, elevation of endogenous polyamine levels by exogenous supply of polyamines, or overexpression of polyamine biosynthetic genes, results in enhanced stress tolerance; and thirdly, a reduction of endogenous polyamines is accompanied by compromised stress tolerance. A number of studies have demonstrated that polyamines function in stress tolerance largely by modulating the homeostasis of reactive oxygen species (ROS due to their direct, or indirect, roles in regulating antioxidant systems or suppressing ROS production. The transcriptional regulation of polyamine synthesis by transcription factors is also reviewed here. Meanwhile, future perspectives on polyamine research are also suggested.

Haploinsufficiency of myostatin protects against aging-related declines in muscle function and enhances the longevity of mice.

Science.gov (United States)

Mendias, Christopher L; Bakhurin, Konstantin I; Gumucio, Jonathan P; Shallal-Ayzin, Mark V; Davis, Carol S; Faulkner, John A

2015-08-01

The molecular mechanisms behind aging-related declines in muscle function are not well understood, but the growth factor myostatin (MSTN) appears to play an important role in this process. Additionally, epidemiological studies have identified a positive correlation between skeletal muscle mass and longevity. Given the role of myostatin in regulating muscle size, and the correlation between muscle mass and longevity, we tested the hypotheses that the deficiency of myostatin would protect oldest-old mice (28-30 months old) from an aging-related loss in muscle size and contractility, and would extend the maximum lifespan of mice. We found that MSTN(+/-) and MSTN(-/-) mice were protected from aging-related declines in muscle mass and contractility. While no differences were detected between MSTN(+/+) and MSTN(-/-) mice, MSTN(+/-) mice had an approximately 15% increase in maximal lifespan. These results suggest that targeting myostatin may protect against aging-related changes in skeletal muscle and contribute to enhanced longevity. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Tomato NAC transcription factor SlSRN1 positively regulates defense response against biotic stress but negatively regulates abiotic stress response.

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Bo Liu

Full Text Available Biotic and abiotic stresses are major unfavorable factors that affect crop productivity worldwide. NAC proteins comprise a large family of transcription factors that play important roles in plant growth and development as well as in responses to biotic and abiotic stresses. In a virus-induced gene silencing-based screening to identify genes that are involved in defense response against Botrytis cinerea, we identified a tomato NAC gene SlSRN1 (Solanum lycopersicum Stress-related NAC1. SlSRN1 is a plasma membrane-localized protein with transactivation activity in yeast. Expression of SlSRN1 was significantly induced by infection with B. cinerea or Pseudomonas syringae pv. tomato (Pst DC3000, leading to 6-8 folds higher than that in the mock-inoculated plants. Expression of SlSRN1 was also induced by salicylic acid, jasmonic acid and 1-amino cyclopropane-1-carboxylic acid and by drought stress. Silencing of SlSRN1 resulted in increased severity of diseases caused by B. cinerea and Pst DC3000. However, silencing of SlSRN1 resulted in increased tolerance against oxidative and drought stresses. Furthermore, silencing of SlSRN1 accelerated accumulation of reactive oxygen species but attenuated expression of defense genes after infection by B. cinerea. Our results demonstrate that SlSRN1 is a positive regulator of defense response against B. cinerea and Pst DC3000 but is a negative regulator for oxidative and drought stress response in tomato.

Calycophyllum spruceanum (Benth., the Amazonian “Tree of Youth” Prolongs Longevity and Enhances Stress Resistance in Caenorhabditis elegans

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Herbenya Peixoto

2018-02-01

Full Text Available The tree popularly known in Brazil as mulateiro or pau-mulato (Calycophyllum spruceanum (Benth. K. Schum. is deeply embedded in the herbal medicine of the Amazon region. Different preparations of the bark are claimed to have anti-aging, antioxidant, antimicrobial, emollient, wound healing, hemostatic, contraceptive, stimulant, and anti-diabetic properties. The current study aims to provide the first step towards a science-based evidence of the beneficial effects of C. spruceanum in the promotion of longevity and in the modulation of age-related markers. For this investigation, we used the model system Caenorhabditis elegans to evaluate in vivo antioxidant and anti-aging activity of a water extract from C. spruceanum. To chemically characterize the extract, HPLC MS (High Performance Liquid Chromatography Mass Spectrometry/MS analyses were performed. Five secondary metabolites were identified in the extract, namely gardenoside, 5-hydroxymorin, cyanidin, taxifolin, and 5-hydroxy-6-methoxycoumarin-7-glucoside. C. spruceanum extract was able to enhance stress resistance and to extend lifespan along with attenuation of aging-associated markers in C. elegans. The demonstrated bioactivities apparently depend on the DAF-16/FOXO pathway. The data might support the popular claims of mulateiro as the “tree of youth”, however more studies are needed to clarify its putative benefits to human health.

Sustainability Cards: Design for Longevity

DEFF Research Database (Denmark)

Hasling, Karen Marie; Ræbild, Ulla

2017-01-01

Product longevity is considered widely as a relevant strategic approach, amongst many, within the field of sustainability. Yet, how to design for increased product lifetime may not be so obvious for practitioners. The complexity of the surrounding issues can constitute a barrier for designers...... for designers and other stakeholders in the design process. The paper is based on a developmental project carried out in the Autumn 2017, within a larger research and collaboration project between raw fur manufacturer Kopenhagen Fur and Design School Kolding investigating sustainability perspectives. The paper...... describes the development of a deck of sustainability cards aiming for product longevity and presents the final deck. Furthermore, the paper contributes with insights on how designers may apply design cards in the design process and how this practice can further sustainable considerations and strategies...

Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins

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Khanichi N. Charles

2017-10-01

Full Text Available Summary: Deterioration of metabolic health is a hallmark of aging and generally assumed to be detrimental to longevity. Exposure to a high-calorie diet impairs metabolism and accelerates aging; conversely, calorie restriction (CR prevents age-related metabolic diseases and extends lifespan. However, it is unclear whether preservation of metabolic health is sufficient to extend lifespan. We utilized a genetic mouse model lacking Fabp4/5 that confers protection against metabolic diseases and shares molecular and lipidomic features with CR to address this question. Fabp-deficient mice exhibit extended metabolic healthspan, with protection against insulin resistance and glucose intolerance, inflammation, deterioration of adipose tissue integrity, and fatty liver disease. Surprisingly, however, Fabp-deficient mice did not exhibit any extension of lifespan. These data indicate that extension of metabolic healthspan in the absence of CR can be uncoupled from lifespan, indicating the potential for independent drivers of these pathways, at least in laboratory mice. : Deterioration of metabolic health is a hallmark of aging and generally thought to be detrimental to longevity. Charles et al. utilize FABP-deficient mice as a model to demonstrate that the preservation of metabolic health in this model persists throughout life, even under metabolic stress, but does not increase longevity. Keywords: fatty acid binding protein, aging, calorie restriction, metabolic health, inflammation, metaflammation, diabetes, obesity, de novo lipogenesis

Positive emotion word use and longevity in famous deceased psychologists.

Science.gov (United States)

Pressman, Sarah D; Cohen, Sheldon

2012-05-01

This study examined whether specific types of positive and negative emotional words used in the autobiographies of well-known deceased psychologists were associated with longevity. For each of the 88 psychologists, the percent of emotional words used in writing was calculated and categorized by valence (positive or negative) and arousal (activated [e.g., lively, anxious] or not activated [e.g., calm, drowsy]) based on existing emotion scales and models of emotion categorization. After controlling for sex, year of publication, health (based on disclosed illness in autobiography), native language, and year of birth, the use of more activated positive emotional words (e.g., lively, vigorous, attentive, humorous) was associated with increased longevity. Negative terms (e.g., angry, afraid, drowsy, sluggish) and unactivated positive terms (e.g., peaceful, calm) were not related to longevity. The association of activated positive emotions with longevity was also independent of words indicative of social integration, optimism, and the other affect/activation categories. Results indicate that in writing, not every type of emotion correlates with longevity and that there may be value to considering different categories beyond emotional valence in health relevant outcomes.

Heritability of and mortality prediction with a longevity phenotype

DEFF Research Database (Denmark)

Sanders, Jason L; Minster, Ryan L; Barmada, M Michael

2014-01-01

Longevity-associated genes may modulate risk for age-related diseases and survival. The Healthy Aging Index (HAI) may be a subphenotype of longevity, which can be constructed in many studies for genetic analysis. We investigated the HAI's association with survival in the Cardiovascular Health Stu...... and heritability in the Long Life Family Study....

SH2B Regulation of Growth, Metabolism, and Longevity in Both Insects and Mammals

OpenAIRE

Song, Wei; Ren, Decheng; Li, Wenjun; Jiang, Lin; Cho, Kae Won; Huang, Ping; Fan, Chen; Song, Yiyun; Liu, Yong; Rui, Liangyou

2010-01-01

SH2B1 is a key regulator of body weight in mammals. Here we identified dSH2B as the Drosophila homolog of SH2B1. dSH2B bound to Chico and directly promoted insulin-like signaling. Disruption of dSH2B decreased insulin-like signaling and somatic growth in flies. dSH2B deficiency also increased hemolymph carbohydrate levels, whole body lipid levels, lifespan, and resistance to starvation and oxidative stress. Systemic overexpression of dSH2B resulted in opposite phenotypes. dSH2B overexpression...

Genetic parameters for longevity in Holteins cows

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Elisa Junqueira Oliveira

2012-12-01

Full Text Available The milk yield has been the most selected trait in dairy cattle breeding programs. However various studies have shown a decline in adaptive and longevity traits in herds that are under selection for improving production, especially in taurine breeds, as the Holstein, who was highly selected for milk production. The aim of this study was to estimate genetic parameters for first lactation 305-day milk yield (Y305 and for longevity traits and to verify the association among them, in high production Holstein cows. The data sets used were from Agrindus Farm, with calving occurring between 1989 and 2005. The traits analyzed were Y305, productive life (PL, calculated as the length of lactation days from the first day of lactation until the culling, and age at culling (AC. Variance components were estimated by Restricted Maximum Likelihood, applying multi-trait animal model. Heritability estimates for Y305, PL and AC were, respectively, 0.35, 0.07 and 0.10. Heritability estimates for PL and AC suggest small genetic variability to get genetic gains by direct selection for these traits, because they are influenced by decisions of voluntary and involuntary culling, being largely affected by factors related to the environment. It is difficult to measure these traits because it is necessary to evaluate culling of animals and causes of culling. The magnitude of the heritability estimate for Y305 evidences the existence of reasonable additive genetic variability, which allows efficiency by selecting for this trait. The genetic correlations between Y305 and PL was 0.02 and between Y305 and AC was 0.01, suggesting small genetic association between Y305 and longevity traits. In this case, the selection for Y305 is viable due to high heritability estimate and the favorable and almost null genetic correlation between Y305 and the longevity traits. Some studies have used to analyze longevity traits as threshold and since this trait has great economic importance, it

Academic Stress and Self-Regulation among University Students in Malaysia: Mediator Role of Mindfulness.

Science.gov (United States)

Hj Ramli, Nur Hamizah; Alavi, Masoumeh; Mehrinezhad, Seyed Abolghasem; Ahmadi, Atefeh

2018-01-15

Academic stress is the most common emotional or mental state that students experience during their studies. Stress is a result of a wide range of issues, including test and exam burden, a demanding course, a different educational system, and thinking about future plans upon graduation. A sizeable body of literature in stress management research has found that self-regulation and being mindful will help students to cope up with the stress and dodge long-term negative consequences, such as substance abuse. The present study aims to investigate the influence of academic stress, self-regulation, and mindfulness among undergraduate students in Klang Valley, Malaysia, and to identify mindfulness as the mediator between academic stress and self-regulation. For this study, a total of 384 undergraduate students in Klang Valley, Malaysia were recruited. Using Correlational analysis, results revealed that there was a significant relationship between academic stress, self-regulation, and mindfulness. However, using SPSS mediational analysis, mindfulness did not prove the mediator role in the study.

Necessity of angiotensin-converting enzyme-related gene for cardiac functions and longevity of Drosophila melanogaster assessed by optical coherence tomography

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Liao, Fang-Tsu; Chang, Cheng-Yi; Su, Ming-Tsan; Kuo, Wen-Chuan

2014-01-01

Prior studies have established the necessity of an angiotensin-converting enzyme-related (ACER) gene for heart morphogenesis of Drosophila. Nevertheless, the physiology of ACER has yet to be comprehensively understood. Herein, we employed RNA interference to down-regulate the expression of ACER in Drosophila's heart and swept source optical coherence tomography to assess whether ACER is required for cardiac functions in living adult flies. Several contractile parameters of Drosophila heart, including the heart rate (HR), end-diastolic diameter (EDD), end-systolic diameter (ESD), percent fractional shortening (%FS), and stress-induced cardiac performance, are shown, which are age dependent. These age-dependent cardiac functions declined significantly when ACER was down-regulated. Moreover, the lifespans of ACER knock-down flies were significantly shorter than those of wild-type control flies. Thus, we posit that ACER, the Drosophila ortholog of mammalian angiotensin-converting enzyme 2 (ACE2), is essential for both heart physiology and longevity of animals. Since mammalian ACE2 controls many cardiovascular physiological features and is implicated in cardiomyopathies, our findings that ACER plays conserved roles in genetically tractable animals will pave the way for uncovering the genetic pathway that controls the renin-angiotensin system.

What are the longevities of teeth and oral implants?

DEFF Research Database (Denmark)

Holm-Pedersen, Poul; Lang, Niklaus P; Müller, Frauke

2007-01-01

To analyse tooth loss and to evaluate the longevity of healthy teeth and teeth compromised by diseases and influenced by therapy as well as that of oral implants.......To analyse tooth loss and to evaluate the longevity of healthy teeth and teeth compromised by diseases and influenced by therapy as well as that of oral implants....

Regulation of water, salinity, and cold stress responses by salicylic acid

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Kenji eMiura

2014-01-01

Full Text Available Salicylic acid (SA is a naturally occurring phenolic compound. SA plays an important role in the regulation of plant growth, development, ripening, and defense responses. The role of SA in the plant-pathogen relationship has been extensively investigated. In addition to defense responses, SA plays an important role in the response to abiotic stresses, including drought, low temperature, and salinity stresses. It has been suggested that SA has great agronomic potential to improve the stress tolerance of agriculturally important crops. However, the utility of SA is dependent on the concentration of the applied SA, the mode of application, and the state of the plants (e.g., developmental stage and acclimation. Generally, low concentrations of applied SA alleviate the sensitivity to abiotic stresses, and high concentrations of applied induce high levels of oxidative stress, leading to a decreased tolerance to abiotic stresses. In this chapter, the effects of SA on the water stress responses and regulation of stomatal closure are reviewed.

Increased Rate of NAD Metabolism Shortens Plant Longevity by Accelerating Developmental Senescence in Arabidopsis.

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Hashida, Shin-Nosuke; Itami, Taketo; Takahara, Kentaro; Hirabayashi, Takayuki; Uchimiya, Hirofumi; Kawai-Yamada, Maki

2016-11-01

NAD is a well-known co-enzyme that mediates hundreds of redox reactions and is the basis of various processes regulating cell responses to different environmental and developmental cues. The regulatory mechanism that determines the amount of cellular NAD and the rate of NAD metabolism remains unclear. We created Arabidopsis thaliana plants overexpressing the NAD synthase (NADS) gene that participates in the final step of NAD biosynthesis. NADS overexpression enhanced the activity of NAD biosynthesis but not the amounts of NAD + , NADH, NADP + or NADPH. However, the amounts of some intermediates were elevated, suggesting that NAD metabolism increased. The NAD redox state was greatly facilitated by an imbalance between NAD generation and degradation in response to bolting. Metabolite profiling and transcriptional analysis revealed that the drastic modulation of NAD redox homeostasis increased tricarboxylic acid flux, causing the ectopic generation of reactive oxygen species. Vascular bundles suffered from oxidative stress, leading to a malfunction in amino acid and organic acid transportation that caused early wilting of the flower stalk and shortened plant longevity, probably due to malnutrition. We concluded that the mechanism regulating the balance between NAD synthesis and degradation is important in the systemic plant response to developmental cues during the growth-phase transition. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The pursuit of longevity - the bringer of peace to the middle East.

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Stambler, Ilia

2014-01-01

Despite the common apprehensions regarding the aging population, this work aims to argue, on both deontological and utilitarian moral grounds, that any increase in general life-expectancy will be beneficial for the Middle East, countering the common fears associated with this increase. A set of ethical arguments concerning increasing longevity is presented, from both the deontological and utilitarian perspective. A wide selection of economic, psychological, demographic and epidemiological literature and databases is analyzed to determine common correlates of extended longevity. On the deontological grounds, the value of extended longevity is derived from the value of life preservation, regardless of its term. On the utilitarian grounds, the value of extended longevity is demonstrated by its correlation with further human values, such as education level and intellectual activity, economic prosperity, equality, solidarity and peacefulness. With the common apprehensions of stagnation and scarcity due to life extension found wanting, the pursuit of longevity by the population can be seen as a cross-cultural and cross-generational good. Though the current study mainly refers to sources and data relevant to the Middle East, a similar pro-longevity argument can be also made for other cultural contexts. In view of its numerous benefits, normatively, the goal of longevity should be set clearly and openly by the society, and actively pursued, or at least discussed, in academia, the political system and broader public.

The challenges in moving from ageing to successful longevity.

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Kolovou, Genovefa; Barzilai, Nir; Caruso, Calogero; Sikora, Ewa; Capri, Miriam; Tzanetakou, Irene P; Bilianou, Helen; Avery, Peter; Katsiki, Niki; Panotopoulos, George; Franceschi, Claudio; Benetos, Athanase; Mikhailidis, Dimitri P

2014-01-01

During the last decades survival has significantly improved and centenarians are becoming a fast-growing group of the population. Human life span is mainly dependent on environmental and genetic factors. Favourable modifications of lifestyle factors (e.g. physical activity, diet and not smoking) and healthcare (e.g. effective vascular disease prevention) have also increased human life span. Genetic factors contribute to the variation of human life span by around 25%, which is believed to be more profound after 85 years of age. It is likely that multiple factors influence life span and we need answers to questions such as: 1) What does it take to reach 100?, 2) Do centenarians have better health during their lifespan compared with contemporaries who died at a younger age?, 3) Do centenarians have protective modifications of body composition, fat distribution and energy expenditure, maintain high physical and cognitive function, and sustained engagement in social and productive activities?, 4) Do centenarians have genes which contribute to longevity?, 5) Do centenarians benefit from epigenetic phenomena?, 6) Is it possible to influence the transgenerational epigenetic inheritance (epigenetic memory) which leads to longevity?, 7) Is the influence of nutrigenomics important for longevity?, 8) Do centenarians benefit more from drug treatment, particularly in primary prevention?, and, 9) Are there any potential goals for drug research? Many definitions of successful ageing have been proposed, but at present there is no consensus definition. Such definitions may need to differentiate between "Longevity Syndrome" and "Exceptional Longevity".

Personality predictors of longevity: activity, emotional stability, and conscientiousness.

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Terracciano, Antonio; Löckenhoff, Corinna E; Zonderman, Alan B; Ferrucci, Luigi; Costa, Paul T

2008-07-01

To examine the association between personality traits and longevity. Using the Guilford-Zimmerman Temperament Survey, personality traits were assessed in 2359 participants (38% women; age = 17 to 98 years, mean = 50 years) from the Baltimore Longitudinal Study of Aging, starting in 1958. Over the duration of the study, 943 (40%) participants died, on average 18 years after their personality assessment. The association of each trait with longevity was examined by Cox regression controlling for demographic variables. In preliminary analyses among the deceased, those who scored 1 standard deviation (SD) above the mean on General Activity (a facet of Extraversion), Emotional Stability (low Neuroticism), or Conscientiousness lived on average 2 to 3 years longer than those scoring 1 SD below the mean. Survival analyses on the full sample confirmed the association of General Activity, Emotional Stability, and Conscientiousness with lower risk of death, such that every 1-SD increase was related to about 13%, 15%, and 27% risk reduction, respectively. The association of personality traits with longevity was largely independent from the influence of smoking and obesity. Personality predictors of longevity did not differ by sex, except for Ascendance (a facet of Extraversion). Emotional Stability was a significant predictor when the analyses were limited to deaths due to cardiovascular disease, with comparable effect sizes for General Activity and Conscientiousness. In a large sample of generally healthy individuals followed for almost five decades, longevity was associated with being conscientious, emotionally stable, and active.

Personality predictors of longevity: Activity, Emotional Stability, and Conscientiousness

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Terracciano, Antonio; Löckenhoff, Corinna E.; Zonderman, Alan B.; Ferrucci, Luigi; Costa, Paul T.

2008-01-01

Objective To examine the association between personality traits and longevity. Methods Using the Guilford-Zimmerman Temperament Survey, personality traits were assessed in 2359 participants (38% women; age: 17 to 98 years, M = 50) from the Baltimore Longitudinal Study of Aging (BLSA), starting in 1958. Over the duration of the study, 943 (40%) participants died, on average 18 years after their personality assessment. The association of each trait with longevity was examined by Cox regression controlling for demographic variables. Results In preliminary analyses among the deceased, those who scored one SD above the mean on General Activity (a facet of Extraversion), Emotional Stability (low Neuroticism), or Conscientiousness lived on average two to three years longer than those scoring one SD below the mean. Survival analyses on the full sample confirmed the association of General Activity, Emotional Stability, and Conscientiousness with lower risk of death, such that every one SD increase was related to about 13%, 15%, and 27% risk reduction, respectively. The association of personality traits with longevity was largely independent from the influence of smoking and obesity. Personality predictors of longevity did not differ by sex, except for Ascendance (a facet of Extraversion). Emotional Stability was a significant predictor when the analyses were limited to deaths due to cardiovascular disease, with comparable effect sizes for General Activity and Conscientiousness. Conclusions In a large sample of generally healthy individuals followed for almost five decades, longevity was associated with being conscientious, emotionally stable, and active. PMID:18596250

Ppargamma2 is a key driver of longevity in the mouse.

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Carmen Argmann

2009-12-01

Full Text Available Aging involves a progressive physiological remodeling that is controlled by both genetic and environmental factors. Many of these factors impact also on white adipose tissue (WAT, which has been shown to be a determinant of lifespan. Interrogating a transcriptional network for predicted causal regulatory interactions in a collection of mouse WAT from F2 crosses with a seed set of 60 known longevity genes, we identified a novel transcriptional subnetwork of 742 genes which represent thus-far-unknown longevity genes. Within this subnetwork, one gene was Pparg (Nr1c3, an adipose-enriched nuclear receptor previously not associated with longevity. In silico, both the PPAR signaling pathway and the transcriptional signature of Ppargamma agonist rosiglitazone overlapped with the longevity subnetwork, while in vivo, lowered expression of Pparg reduced lifespan in both the lipodystrophic Pparg1/2-hypomorphic and the Pparg2-deficient mice. These results establish Ppargamma2 as one of the determinants of longevity and suggest that lifespan may be rather determined by a purposeful genetic program than a random process.

Running as a Key Lifestyle Medicine for Longevity.

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Lee, Duck-Chul; Brellenthin, Angelique G; Thompson, Paul D; Sui, Xuemei; Lee, I-Min; Lavie, Carl J

Running is a popular and convenient leisure-time physical activity (PA) with a significant impact on longevity. In general, runners have a 25%-40% reduced risk of premature mortality and live approximately 3 years longer than non-runners. Recently, specific questions have emerged regarding the extent of the health benefits of running versus other types of PA, and perhaps more critically, whether there are diminishing returns on health and mortality outcomes with higher amounts of running. This review details the findings surrounding the impact of running on various health outcomes and premature mortality, highlights plausible underlying mechanisms linking running with chronic disease prevention and longevity, identifies the estimated additional life expectancy among runners and other active individuals, and discusses whether there is adequate evidence to suggest that longevity benefits are attenuated with higher doses of running. Copyright © 2017 Elsevier Inc. All rights reserved.

[Regulation of heat shock gene expression in response to stress].

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Garbuz, D G

2017-01-01

Heat shock (HS) genes, or stress genes, code for a number of proteins that collectively form the most ancient and universal stress defense system. The system determines the cell capability of adaptation to various adverse factors and performs a variety of auxiliary functions in normal physiological conditions. Common stress factors, such as higher temperatures, hypoxia, heavy metals, and others, suppress transcription and translation for the majority of genes, while HS genes are upregulated. Transcription of HS genes is controlled by transcription factors of the HS factor (HSF) family. Certain HSFs are activated on exposure to higher temperatures or other adverse factors to ensure stress-induced HS gene expression, while other HSFs are specifically activated at particular developmental stages. The regulation of the main mammalian stress-inducible factor HSF1 and Drosophila melanogaster HSF includes many components, such as a variety of early warning signals indicative of abnormal cell activity (e.g., increases in intracellular ceramide, cytosolic calcium ions, or partly denatured proteins); protein kinases, which phosphorylate HSFs at various Ser residues; acetyltransferases; and regulatory proteins, such as SUMO and HSBP1. Transcription factors other than HSFs are also involved in activating HS gene transcription; the set includes D. melanogaster GAF, mammalian Sp1 and NF-Y, and other factors. Transcription of several stress genes coding for molecular chaperones of the glucose-regulated protein (GRP) family is predominantly regulated by another stress-detecting system, which is known as the unfolded protein response (UPR) system and is activated in response to massive protein misfolding in the endoplasmic reticulum and mitochondrial matrix. A translational fine tuning of HS protein expression occurs via changing the phosphorylation status of several proteins involved in translation initiation. In addition, specific signal sequences in the 5'-UTRs of some HS

The interactive role of eating regulation and stress in the prediction of weight-related outcomes among college students.

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Arsiwalla, Dilbur D; Arnold, Amanda W; Teel, Karla P; Ulrich, Pamela V; Gropper, Sareen S

2018-02-01

The interactive role of eating regulation and perceived stress on weight-related outcomes was examined among 319 sophomore year college students (110 males and 209 females). Moderated regressions were used to examine interactions between stress and eating regulation on study outcomes including body mass index (BMI) and body fat. Eating regulation moderated associations between stress and BMI and body fat outcomes. Students reporting high perceived stress, high autonomous eating regulation, low controlled regulation, and low amotivation exhibited higher outcomes (BMI and body fat) than those with similar eating regulation but lower perceived stress. Students with lower autonomous eating regulation and higher controlled regulation had no differences in study outcomes across levels of stress. College students who regulate their eating behaviours for health reasons (specifically showing autonomous regulation) exhibit higher BMI and body fat when they report higher levels of perceived stress. Health promotion programs for college students need to target education efforts towards stress reduction and healthy eating behaviours. Copyright © 2017 John Wiley & Sons, Ltd.

Analysis of implantable defibrillator longevity under clinical circumstances: implications for device selection.

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Knops, Paul; Theuns, Dominic A M J; Res, Jan C J; Jordaens, Luc

2009-10-01

Information about implantable cardioverter-defibrillator (ICD) longevity is mostly calculated from measurements under ideal laboratory conditions. However, little information about longevity under clinical circumstances is available. This survey gives an overview on ICD service times and generator replacements in a cohort of consecutive ICD patients. Indications for replacement were classified as a normal end-of-service (EOS), premature EOS, system malfunction, infection and device advisory, or recall actions. From the premature and normal EOS group, longevity from single-chamber (SC), dual-chamber (DC), and cardiac resynchronization therapy defibrillator (CRT-D), rate-responsive (RR) settings, high output (HO) stimulation, and indication for ICD therapy was compared. Differences between brands were compared as well. In a total of 854 patients, 203 ICD replacements (165 patients) were recorded. Premature and normal EOS replacements consisted of 32 SC, 98 DC and 24 CRT-D systems. Longevity was significantly longer in SC systems compared to DC and CRT-D systems (54 +/- 19 vs. 40 +/- 17 and 42 +/- 15 months; P = 0.008). Longevity between non-RR (n = 143) and RR (n = 11) settings was not significantly different (43 +/- 18 vs. 45 +/- 13 months) as it also was not for HO versus non-HO stimulation (43 +/- 19 vs. 46 +/- 17 months). Longevity of ICDs was not significantly different between primary and secondary prevention (42 +/- 19 vs. 44 +/- 18 months). The average longevity on account of a device-based EOS message was 43 +/- 18 months. Average longevity for Biotronik (BIO, n = 72) was 33 +/- 10 months, for ELA Medical (ELA, n = 12) 44 +/- 17 months, for Guidant (GDT, n = 36) 49 +/- 12 months, for Medtronic (MDT, n = 29) 62 +/- 22 months, and for St. Jude Medical (SJM, n = 5) 31 +/- 9 months (P generators had a longer service time compared to DC and CRT-D systems. No influence of indication for ICD therapy and HO stimulation on generator longevity was observed in this

Therapeutic landscapes and longevity: Wellness tourism in Bama.

Science.gov (United States)

Huang, Liyuan; Xu, Honggang

2018-01-01

Due to the rising demand for healthcare products and concern over environmental pollution, wellness tourism has been booming in China in recent years. The therapeutic landscape theory provides a multi-scale interpretation of wellness tourism to explore how wellness tourists achieve health in healing places. By presenting the results of 83 interviews conducted in Bama, China, this study reveals that the "longevity village" Bama, endorsed by centenarians, provides a retreat that combines natural beauty and a harmonious neighbourhood for wellness tourists. This article argues that although three themes-natural environment, social interaction and symbolic landscape-work together in the healing process of tourists, the symbolic landscape, which is significantly shaped by the longevity culture, plays a dominant role. Longevity in Chinese culture symbolizes the alignment of a strong body, graceful mind, and pleasant habitat. Furthermore, tourism reinforces the importance of symbols and imagination (of a place), the perception of longevity demonstrates the symbolic landscape and thus increases tourists' attachment to the place, and the unusual environment leads to a different therapeutic landscape from that of daily life. Finally, since to date there has been very few works on therapeutic landscapes in China, it is expected that this study will fill the knowledge gap and broaden the scope of application as well as conceptualization of the therapeutic landscape. Copyright © 2017 Elsevier Ltd. All rights reserved.

Strong social relationships are associated with decreased longevity in a facultatively social mammal.

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Blumstein, Daniel T; Williams, Dana M; Lim, Alexandra N; Kroeger, Svenja; Martin, Julien G A

2018-01-31

Humans in strong social relationships are more likely to live longer because social relationships may buffer stressors and thus have protective effects. However, a shortcoming of human studies is that they often rely on self-reporting of these relationships. By contrast, observational studies of non-human animals permit detailed analyses of the specific nature of social relationships. Thus, discoveries that some social animals live longer and healthier lives if they are involved in social grooming, forage together or have more affiliative associates emphasizes the potential importance of social relationships on health and longevity. Previous studies have focused on the impact of social metrics on longevity in obligately social species. However, if sociality indeed has a key role in longevity, we might expect that affiliative relationships should also influence longevity in less social species. We focused on socially flexible yellow-bellied marmots ( Marmota flaviventer ) and asked whether female longevity covaries with the specific nature of social relationships. We quantified social relationships with social network statistics that were based on affiliative interactions, and then estimated the correlation between longevity and sociality using bivariate models. We found a significant negative phenotypic correlation between affiliative social relationship strength and longevity; marmots with greater degree, closeness and those with a greater negative average shortest path length died at younger ages. We conclude that sociality plays an important role in longevity, but how it does so may depend on whether a species is obligately or facultatively social. © 2018 The Author(s).

Effect of interleukin-6 polymorphisms on human longevity

DEFF Research Database (Denmark)

Di Bona, Danilo; Vasto, Sonya; Capurso, Cristiano

2009-01-01

-6 levels. However, discordant results have been obtained. To explore the relationship between this polymorphism and longevity, we analyzed individual data on long-living subjects and controls from eight case-control studies conducted in Europeans, using meta-analysis. There was no significant...... two times less likely to reach extreme old age compared with subjects carrying CC or CG genotypes. These findings were not replicated in other European groups suggesting a possible interaction between genetics, sex and environment in reaching longevity....

Familial Longevity Is Marked by Better Cognitive Performance at Middle Age: The Leiden Longevity Study

NARCIS (Netherlands)

Stijntjes, M.; Craen, A.J.M.; van Heemst, D.; Meskers, C.G.M.; van Buchem, M.A.; Westendorp, R.G.J.; Slagboom, P.E.; Maier, A.B.

2013-01-01

Background: Decline in cognitive performance is a highly prevalent health condition in elderly. We studied whether offspring of nonagenarian siblings with a familial history of longevity, perform better on cognitive tests compared to their partners as controls. This is relevant since it could

The role of the TOR pathway in mediating the link between nutrition and longevity.

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Lushchak, Oleh; Strilbytska, Olha; Piskovatska, Veronika; Storey, Kenneth B; Koliada, Alexander; Vaiserman, Alexander

2017-06-01

The target of rapamycin (TOR) pathway integrates signals from extracellular and intracellular agents, such as growth factors, nutrients, mediators of energy balance, oxygen availability and other environmental cues. It allows the regulation of multiple cellular processes including protein and lipid synthesis, ribosome biogenesis, autophagy and metabolic processes. Being conserved across different phyla, TOR regulates longevity of various organisms in response to dietary conditions. In this review we described the main components of the TOR pathway and its upstream effectors and downstream processes in relation to aging. The potential contribution of the TOR pathway in lifespan-extending effects of varied dietary interventions, and the anti-aging drugs rapamycin and metformin direct or indirect regulation of TOR activity in yeasts, worms, flies and mammals are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

The microbiome: A key regulator of stress and neuroinflammation

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Kieran Rea

2016-10-01

In this review, the involvement of the gastrointestinal microbiota in stress-mediated and immune-mediated modulation of neuroendocrine, immune and neurotransmitter systems and the consequential behaviour is considered. We also focus on the mechanisms by which commensal gut microbiota can regulate neuroinflammation and further aim to exploit our understanding of their role in stress-related disorders as a consequence of neuroinflammatory processes.

Assortative Mating by Ethnicity in Longevous Families

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Paola Sebastiani

2017-11-01

Full Text Available Recent work shows strong evidence of ancestry-based assortative mating in spouse pairs of the older generation of the Framingham Heart Study. Here, we extend this analysis to two studies of human longevity: the Long Life Family Study (LLFS, and the New England Centenarian Study (NECS. In the LLFS, we identified 890 spouse pairs spanning two generations, while in the NECS we used data from 102 spouse pairs including offspring of centenarians. We used principal components of genome-wide genotype data to demonstrate strong evidence of ancestry-based assortative mating in spouse pairs of the older generation and also confirm the decreasing trend of endogamy in more recent generations. These findings in studies of human longevity suggest that spouses marrying into longevous families may not be powerful controls for genetic association studies, and that there may be important ethnicity-specific, genetic influences and/or gene–environment interactions that influence extreme survival in old generations. In addition, the decreasing trend of genetic similarity of more recent generations might have ramifications for the incidence of homozygous rare variants necessary for survival to the most extreme ages.

Assortative Mating by Ethnicity in Longevous Families.

Science.gov (United States)

Sebastiani, Paola; Gurinovich, Anastasia; Bae, Harold; Andersen, Stacy L; Perls, Thomas T

2017-01-01

Recent work shows strong evidence of ancestry-based assortative mating in spouse pairs of the older generation of the Framingham Heart Study. Here, we extend this analysis to two studies of human longevity: the Long Life Family Study (LLFS), and the New England Centenarian Study (NECS). In the LLFS, we identified 890 spouse pairs spanning two generations, while in the NECS we used data from 102 spouse pairs including offspring of centenarians. We used principal components of genome-wide genotype data to demonstrate strong evidence of ancestry-based assortative mating in spouse pairs of the older generation and also confirm the decreasing trend of endogamy in more recent generations. These findings in studies of human longevity suggest that spouses marrying into longevous families may not be powerful controls for genetic association studies, and that there may be important ethnicity-specific, genetic influences and/or gene-environment interactions that influence extreme survival in old generations. In addition, the decreasing trend of genetic similarity of more recent generations might have ramifications for the incidence of homozygous rare variants necessary for survival to the most extreme ages.

Adaptations to a Subterranean Environment and Longevity Revealed by the Analysis of Mole Rat Genomes

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Xiaodong Fang

2014-09-01

Full Text Available Subterranean mammals spend their lives in dark, unventilated environments that are rich in carbon dioxide and ammonia and low in oxygen. Many of these animals are also long-lived and exhibit reduced aging-associated diseases, such as neurodegenerative disorders and cancer. We sequenced the genome of the Damaraland mole rat (DMR, Fukomys damarensis and improved the genome assembly of the naked mole rat (NMR, Heterocephalus glaber. Comparative genome analyses, along with the transcriptomes of related subterranean rodents, revealed candidate molecular adaptations for subterranean life and longevity, including a divergent insulin peptide, expression of oxygen-carrying globins in the brain, prevention of high CO2-induced pain perception, and enhanced ammonia detoxification. Juxtaposition of the genomes of DMR and other more conventional animals with the genome of NMR revealed several truly exceptional NMR features: unusual thermogenesis, an aberrant melatonin system, pain insensitivity, and unique processing of 28S rRNA. Together, these genomes and transcriptomes extend our understanding of subterranean adaptations, stress resistance, and longevity.

Apolipoprotein E and familial longevity

DEFF Research Database (Denmark)

Schupf, Nicole; Barral, Sandra; Perls, Thomas

2013-01-01

Exceptional longevity is associated with substantial heritability. The ε4 allele in apolipoprotein E and the linked G allele in rs2075650 of TOMM40 have been associated with increased mortality and the ε2 allele with decreased mortality, although inconsistently. Offspring from long-lived families...

The GATA transcription factor egl-27 delays aging by promoting stress resistance in Caenorhabditis elegans.

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Xiao Xu

Full Text Available Stress is a fundamental aspect of aging, as accumulated damage from a lifetime of stress can limit lifespan and protective responses to stress can extend lifespan. In this study, we identify a conserved Caenorhabditis elegans GATA transcription factor, egl-27, that is involved in several stress responses and aging. We found that overexpression of egl-27 extends the lifespan of wild-type animals. Furthermore, egl-27 is required for the pro-longevity effects from impaired insulin/IGF-1 like signaling (IIS, as reduced egl-27 activity fully suppresses the longevity of worms that are mutant for the IIS receptor, daf-2. egl-27 expression is inhibited by daf-2 and activated by pro-longevity factors daf-16/FOXO and elt-3/GATA, suggesting that egl-27 acts at the intersection of IIS and GATA pathways to extend lifespan. Consistent with its role in IIS signaling, we found that egl-27 is involved in stress response pathways. egl-27 expression is induced in the presence of multiple stresses, its targets are significantly enriched for many types of stress genes, and altering levels of egl-27 itself affects survival to heat and oxidative stress. Finally, we found that egl-27 expression increases between young and old animals, suggesting that increased levels of egl-27 in aged animals may act to promote stress resistance. These results identify egl-27 as a novel factor that links stress and aging pathways.

Application of gamma radiation on longevity of some mites species (Acari: Tetranychidade)

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Machi, Andre R., E-mail: rica_machi@hotmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Arthur, Valter, E-mail: arthur@cena.usp.br [Centro de Energia Nuclear na Agricultura (CENA/USP), Piracicaba, SP (Brazil)

2015-07-01

Mites are pests agricultural found in various environments accessible to animal life: soil, aerial parts of the plants, host insects. In this research the effects of gamma irradiation on longevity of mite pests of the tetranychidae family have been studied. The mites were irradiated in a source of Cobalt-60, Gammacell-220 type, at a dose rate of 0.486 kGy located in the CENA/USP, in the doses of 0 (control), 100, 200, 300, and 400 Gy with sixteen replicates per dose. After the irradiation, the mites were placed in petri dishes totalizing 5 treatments in 32 repetitions. The analysis of variance design with completely randomized design using the Statistical Analysis System (SAS) and the Tukey test, the verification of means. Were evaluated daily the adult mortality and longevity of irradiated mites. After 25 days was observed a mean longevity of mites, for O.ilicis, 100 Gy was equal the control dose (18.3 days), but to T. desertorum and T. urticae the larger longevity was observed in the dose of 200 Gy (19.0 days) being that this dose, obtained the larger longevity in comparison to control dose (18.5 days), in general the longevity decreased in relation to increased doses. Thus, only the dose of 100 Gy and 200 Gy stimulated an increased the longevity in O. ilicis and T. desertorum and T. urticae respectively. The exact mechanism by which the mites are tolerant to avoid damage caused by radicals when exposed to ionizing radiation is not fully understood. (author)

Application of gamma radiation on longevity of some mites species (Acari: Tetranychidade)

International Nuclear Information System (INIS)

Machi, Andre R.; Arthur, Valter

2015-01-01

Mites are pests agricultural found in various environments accessible to animal life: soil, aerial parts of the plants, host insects. In this research the effects of gamma irradiation on longevity of mite pests of the tetranychidae family have been studied. The mites were irradiated in a source of Cobalt-60, Gammacell-220 type, at a dose rate of 0.486 kGy located in the CENA/USP, in the doses of 0 (control), 100, 200, 300, and 400 Gy with sixteen replicates per dose. After the irradiation, the mites were placed in petri dishes totalizing 5 treatments in 32 repetitions. The analysis of variance design with completely randomized design using the Statistical Analysis System (SAS) and the Tukey test, the verification of means. Were evaluated daily the adult mortality and longevity of irradiated mites. After 25 days was observed a mean longevity of mites, for O.ilicis, 100 Gy was equal the control dose (18.3 days), but to T. desertorum and T. urticae the larger longevity was observed in the dose of 200 Gy (19.0 days) being that this dose, obtained the larger longevity in comparison to control dose (18.5 days), in general the longevity decreased in relation to increased doses. Thus, only the dose of 100 Gy and 200 Gy stimulated an increased the longevity in O. ilicis and T. desertorum and T. urticae respectively. The exact mechanism by which the mites are tolerant to avoid damage caused by radicals when exposed to ionizing radiation is not fully understood. (author)

Is extreme climate or moderate climate more conducive to longevity in China?

Science.gov (United States)

Huang, Yi; Rosenberg, Mark; Wang, Yingli

2018-02-01

Climate is closely related to human longevity. In China, there are many climate types. According to national population censuses from 1982 to 2000, most provinces with a high ratio of centenarians are located in western and northwestern China far from the sea; these areas are characterized by a dry, cold climate, very high altitude, very high daily temperature range, strong winds, and partial hypoxia. Meanwhile, provinces with a high ratio of nonagenarians from 1982 to 2000 are located in southern China near the sea. Previous studies have attributed the high ratio of centenarians in western and northwestern China to the extreme local climate. However, centenarians in these areas decreased greatly in 2010, whereas residents in southern China frequently reached 90 to 100 years old in 2010. This study aims to explain this strange phenomenon and find whether extreme climate in Tibetan plateau and northwestern China or moderate climate in southern China is more conducive to longevity. The study found that mortality rate in Tibetan plateau is much higher than southern China, then a population evolution experiment was proposed to compare longevity indicators between low mortality rate and high mortality rate and shows that longevity indicators will decrease in the near future and increase above their original levels after several decades when the mortality rate is decreased. Results of this study show individuals in northwestern China do not live as long as those in eastern and southern China. A moderate climate is more conducive to longevity than extreme climate in China. The longevity of a region should be judged by long-term longevity indicators.

Adult Literacy Education Program Administrators' Perceptions of Occupational Stress and Coping Mechanisms

Science.gov (United States)

Engelmann, Stephanie

2014-01-01

Job performance may be adversely affected by stress. Job stress is a primary contributor to serious physical and emotional health consequences. This quantitative study examined adult literacy program administrator perceptions of occupational stress and coping mechanisms related to job satisfaction, job efficacy, career longevity, and overall…

Molecular markers as a tool for breeding for flower longevity in Asiatic hybrid lilies.

NARCIS (Netherlands)

Meulen, van der J.J.M.; Oeveren, van J.C.; Sandbrink, J.M.; Tuyl, van J.M.

1996-01-01

Segregation of flower longevity in two lily populations was studied and the genetic linkage of morphological markers and RAPD markers with loci involved in flower longevity was investigated. A large variation in flower longevity was found within the two populations tested at individual plant level.

The longevity of gerontologists.

Science.gov (United States)

Freeman, J T

1975-05-01

The forces of mortality are the prime determinants of longevity. Longevity is a basic consideration of gerontology and includes the life expectancy of the species, the average expectancy of survival at birth, and the average of lifespan. In the history of the study of old age, for which the modern period began about 1930, there are no reports of the average lifespan for the students of aging. A survey revealed that the average lifespan of 28 special groups (15,000 individuals) was 68 years; this included an average of 68.01 years for 394 gerontologists during the same eras. These figures are comparable because the attainment of a particular status in a profession or vocation is evidence of survival to maturity. Comparison could not be made with data for the general population whose vital statistics begin at birth. The average duration of life for men whose work in part or in whole prior to the 20th century was in gerontology falls midway between the high level of 77 years for classical Greek authors and the low level of 51 years for revolutionary statesmen, and exactly between the levels of life duration for eunuchs and physical and medical scientists.

Evolution of stress-regulated gene expression in duplicate genes of Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Cheng Zou

2009-07-01

Full Text Available Due to the selection pressure imposed by highly variable environmental conditions, stress sensing and regulatory response mechanisms in plants are expected to evolve rapidly. One potential source of innovation in plant stress response mechanisms is gene duplication. In this study, we examined the evolution of stress-regulated gene expression among duplicated genes in the model plant Arabidopsis thaliana. Key to this analysis was reconstructing the putative ancestral stress regulation pattern. By comparing the expression patterns of duplicated genes with the patterns of their ancestors, duplicated genes likely lost and gained stress responses at a rapid rate initially, but the rate is close to zero when the synonymous substitution rate (a proxy for time is > approximately 0.8. When considering duplicated gene pairs, we found that partitioning of putative ancestral stress responses occurred more frequently compared to cases of parallel retention and loss. Furthermore, the pattern of stress response partitioning was extremely asymmetric. An analysis of putative cis-acting DNA regulatory elements in the promoters of the duplicated stress-regulated genes indicated that the asymmetric partitioning of ancestral stress responses are likely due, at least in part, to differential loss of DNA regulatory elements; the duplicated genes losing most of their stress responses were those that had lost more of the putative cis-acting elements. Finally, duplicate genes that lost most or all of the ancestral responses are more likely to have gained responses to other stresses. Therefore, the retention of duplicates that inherit few or no functions seems to be coupled to neofunctionalization. Taken together, our findings provide new insight into the patterns of evolutionary changes in gene stress responses after duplication and lay the foundation for testing the adaptive significance of stress regulatory changes under highly variable biotic and abiotic environments.

Influence of internal current and pacing current on pacemaker longevity.

Science.gov (United States)

Schuchert, A; Kuck, K H

1994-01-01

The effects of lower pulse amplitude on battery current and pacemaker longevity were studied comparing the new, small-sized VVI pacemaker, Minix 8341, with the former model, Pasys 8329. Battery current was telemetrically measured at 0.8, 1.6, 2.5, and 5.0 V pulse amplitude and 0.05, 0.25, 0.5, and 1.0 msec pulse duration. Internal current was assumed to be equal to the battery current at 0.8 V and 0.05 msec. Pacing current was calculated subtracting internal current from battery current. The Minix pacemaker had a significantly lower battery current because of a lower internal current (Minix: 4.1 +/- 0.1 microA; Pasys: 16.1 +/- 0.1 microA); pacing current of both units was similar. At 0.5 msec pulse duration, the programming from 5.0-2.5 V pulse amplitude resulted in a greater relative reduction of battery current in the newer pacemaker (51% vs 25%). Projected longevity of each pacemaker was 7.9 years at 5.0 V and 0.5 msec. The programming from 5.0-2.5 V extended the projected longevity by 2.3 years (Pasys) and by 7.1 years (Minix). The longevity was negligibly longer after programming to 1.6 V. extension of pacemaker longevity can be achieved with the programming to 2.5 V or less if the connected pacemakers need a low internal current for their circuitry.

The Role of Stress Regulation on Neural Plasticity in Pain Chronification.

Science.gov (United States)

Li, Xiaoyun; Hu, Li

2016-01-01

Pain, especially chronic pain, is one of the most common clinical symptoms and has been considered as a worldwide healthcare problem. The transition from acute to chronic pain is accompanied by a chain of alterations in physiology, pathology, and psychology. Increasing clinical studies and complementary animal models have elucidated effects of stress regulation on the pain chronification via investigating activations of the hypothalamic-pituitary-adrenal (HPA) axis and changes in some crucial brain regions, including the amygdala, prefrontal cortex, and hippocampus. Although individuals suffer from acute pain benefit from such physiological alterations, chronic pain is commonly associated with maladaptive responses, like the HPA dysfunction and abnormal brain plasticity. However, the causal relationship among pain chronification, stress regulation, and brain alterations is rarely discussed. To call for more attention on this issue, we review recent findings obtained from clinical populations and animal models, propose an integrated stress model of pain chronification based on the existing models in perspectives of environmental influences and genetic predispositions, and discuss the significance of investigating the role of stress regulation on brain alteration in pain chronification for various clinical applications.

Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

Directory of Open Access Journals (Sweden)

Ji-Ming Bao

2014-06-01

Full Text Available Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs and 95% confidence intervals (CIs were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR = 1.36, 95% CI = 1.10-1.69, P= 0.005; OR = 1.20, 95% CI = 1.04-1.37, P= 0.01; OR = 1.27, 95% CI = 1.10-1.46, P= 0.001; OR = 1.14, 95% CI = 1.01-1.27 and OR = 1.24, 95% CI = 1.07-1.43, P= 0.003, respectively. Analysis stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR = 1.54, 95% CI = 1.33-1.79, P < 0.001; OR = 1.38, 95% CI = 1.15-1.66, P= 0.001; and OR = 1.39, 95% CI = 1.15-1.67, P= 0.001, but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a significant association of five FOXO3A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis.

Science.gov (United States)

Bao, Ji-Ming; Song, Xian-Lu; Hong, Ying-Qia; Zhu, Hai-Li; Li, Cui; Zhang, Tao; Chen, Wei; Zhao, Shan-Chao; Chen, Qing

2014-01-01

Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR = 1.36, 95% CI = 1.10-1.69, P= 0.005; OR = 1.20, 95% CI = 1.04-1.37, P= 0.01; OR = 1.27, 95% CI = 1.10-1.46, P= 0.001; OR = 1.14, 95% CI = 1.01-1.27 and OR = 1.24, 95% CI = 1.07-1.43, P= 0.003, respectively). Analysis stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR = 1.54, 95% CI = 1.33-1.79, P < 0.001; OR = 1.38, 95% CI = 1.15-1.66, P= 0.001; and OR = 1.39, 95% CI = 1.15-1.67, P= 0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a significant association of five FOXO3A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

Exceptional longevity in female Rottweiler dogs is not encumbered by investment in reproduction.

Science.gov (United States)

Kengeri, S S; Maras, A H; Suckow, C L; Chiang, E C; Waters, D J

2013-12-01

To better understand the potential trade-off between female reproductive investment and longevity in an emerging model of human healthspan, we studied pet dogs to determine whether intensity of reproduction (total number of offspring) encumbered the likelihood of exceptional longevity. This hypothesis was tested by collecting and analyzing lifetime medical histories, including complete reproductive histories, for a cohort of canine "centenarians"--exceptionally long-lived Rottweiler dogs that lived more than 30% longer than the breed's average life expectancy. Reproductive intensity (number of litters, total number of pups) and tempo of reproductive effort (age at first reproduction, mean interbirth interval, age at last reproduction) in 78 exceptionally long-lived female Rottweilers (>13 years old) were compared to a cohort of 97 female Rottweilers that had usual longevity (age at death 8.0-10.75 years). We found no evidence that a mother's physiological investment in offspring was associated with disadvantaged longevity. Instead, similar to some studies in women, our data showed an inverted U-shaped trend, suggesting that moderate investment in reproduction may promote longevity. Late reproductive success, a much-studied surrogate of maternal fitness in women, was not a strong predictor of longevity in this canine cohort. Instead, independent of reproductive investment, the duration of lifetime ovary exposure was significantly associated with highly successful aging. Our results from exceptionally long-lived pet dogs provide rationale for further investigative efforts to understand the ovary-sensitive biological factors that promote healthy longevity in women and pet dogs.

Regulation of Adult Neurogenesis and Plasticity by (Early) Stress, Glucocorticoids, and Inflammation

NARCIS (Netherlands)

Lucassen, P.J.; Oomen, C.A.; Naninck, E.F.G.; Fitzsimons, C.P.; van Dam, A.M.; Czeh, B.; Korosi, A.

2015-01-01

Exposure to stress is one of the best-known negative regulators of adult neurogenesis (AN). We discuss changes in neurogenesis in relation to exposure to stress, glucocorticoid hormones, and inflammation, with a particular focus on early development and on lasting effects of stress. Although the

The effect of floral resources on parasitoid and host longevity

DEFF Research Database (Denmark)

Sigsgaard, Lene; Betzer, Cathrine; Naulin, Cyril

2013-01-01

The strawberry tortricid, Acleris comariana Lienig and Zeller(Lepidoptera: Tortricidae)is an important pest in Danish strawberry production. Its most common parasitoid is Copidosoma aretas (Walker) (Hymenoptera: Chalcidoidea: Encyrtidae). To identify selective flowering plants that could be used...... to increase functional biodiversity, the longevity of C. aretas and its host A. comariana was assessed on 5 flowering species: buckwheat, Fagopyrum esculentum Moench (Caryophyllales: Polygonaceae); borage, Borago officinalis L. (Boraginaceae); strawberry, Fragaria x ananassa Duchesne (Rosales: Rosaceae...... buckwheat also increased longevity of A. comariana, its longevity and survival on buckwheat, borage, and strawberry was not significantly different, so buckwheat was chosen for field experiments. A. comariana densities in the 3 fields with sown buckwheat flower strips were 0.5, 4.0, and 8.3 larvae per m per...

Exercise and longevity.

Science.gov (United States)

Gremeaux, Vincent; Gayda, Mathieu; Lepers, Romuald; Sosner, Philippe; Juneau, Martin; Nigam, Anil

2012-12-01

Aging is a natural and complex physiological process influenced by many factors, some of which are modifiable. As the number of older individuals continues to increase, it is important to develop interventions that can be easily implemented and contribute to "successful aging". In addition to a healthy diet and psychosocial well-being, the benefits of regular exercise on mortality, and the prevention and control of chronic disease affecting both life expectancy and quality of life are well established. We summarize the benefits of regular exercise on longevity, present the current knowledge regarding potential mechanisms, and outline the main recommendations. Exercise can partially reverse the effects of the aging process on physiological functions and preserve functional reserve in the elderly. Numerous studies have shown that maintaining a minimum quantity and quality of exercise decreases the risk of death, prevents the development of certain cancers, lowers the risk of osteoporosis and increases longevity. Training programs should include exercises aimed at improving cardiorespiratory fitness and muscle function, as well as flexibility and balance. Though the benefits of physical activity appear to be directly linked to the notion of training volume and intensity, further research is required in the elderly, in order to develop more precise recommendations, bearing in mind that the main aim is to foster long-term adherence to physical activity in this growing population. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity.

Directory of Open Access Journals (Sweden)

J R Managbanag

Full Text Available BACKGROUND: Identification of genes that modulate longevity is a major focus of aging-related research and an area of intense public interest. In addition to facilitating an improved understanding of the basic mechanisms of aging, such genes represent potential targets for therapeutic intervention in multiple age-associated diseases, including cancer, heart disease, diabetes, and neurodegenerative disorders. To date, however, targeted efforts at identifying longevity-associated genes have been limited by a lack of predictive power, and useful algorithms for candidate gene-identification have also been lacking. METHODOLOGY/PRINCIPAL FINDINGS: We have utilized a shortest-path network analysis to identify novel genes that modulate longevity in Saccharomyces cerevisiae. Based on a set of previously reported genes associated with increased life span, we applied a shortest-path network algorithm to a pre-existing protein-protein interaction dataset in order to construct a shortest-path longevity network. To validate this network, the replicative aging potential of 88 single-gene deletion strains corresponding to predicted components of the shortest-path longevity network was determined. Here we report that the single-gene deletion strains identified by our shortest-path longevity analysis are significantly enriched for mutations conferring either increased or decreased replicative life span, relative to a randomly selected set of 564 single-gene deletion strains or to the current data set available for the entire haploid deletion collection. Further, we report the identification of previously unknown longevity genes, several of which function in a conserved longevity pathway believed to mediate life span extension in response to dietary restriction. CONCLUSIONS/SIGNIFICANCE: This work demonstrates that shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity and represents the first application of

A novel sampling design to explore gene-longevity associations

DEFF Research Database (Denmark)

De Rango, Francesco; Dato, Serena; Bellizzi, Dina

2008-01-01

To investigate the genetic contribution to familial similarity in longevity, we set up a novel experimental design where cousin-pairs born from siblings who were concordant or discordant for the longevity trait were analyzed. To check this design, two chromosomal regions already known to encompass...... from concordant and discordant siblings. In addition, we analyzed haplotype transmission from centenarians to offspring, and a statistically significant Transmission Ratio Distortion (TRD) was observed for both chromosomal regions in the discordant families (P=0.007 for 6p21.3 and P=0.015 for 11p15.......5). In concordant families, a marginally significant TRD was observed at 6p21.3 only (P=0.06). Although no significant difference emerged between the two groups of cousin-pairs, our study gave new insights on the hindrances to recruiting a suitable sample to obtain significant IBD data on longevity...

Longevity of Emplacement Drift Ground Support Materials, Rev. 01

International Nuclear Information System (INIS)

David H. Tang

2000-01-01

The purpose of this analysis is to evaluate the factors affecting the longevity of emplacement drift ground support materials and to develop a basis for the selection of materials for ground support that will function throughout the preclosure period of a potential repository at Yucca Mountain. The Development Plan (DP) for this analysis is given in Longevity of Emplacement Drift Ground Support Materials (CRWMS M and O 1999a). The objective of this analysis is to update the previous analysis (CRWMS M and O 2000a) to account for related changes in the Ground Control System Description Document (CRWMS M and O 2000b), the Monitored Geologic Repository Project Description Document (CRWMS M and O 1999b), and in environmental conditions, and to provide updated information on candidate ground support materials. Candidate materials for ground support are carbon steel and cement grout. Steel is mainly used for steel sets, lagging, channel, rock bolts, and wire mesh. Cement grout is only considered in the case of grouted rock bolts. Candidate materials for the emplacement drift invert are carbon steel and crushed rock ballast. Materials are evaluated for the repository emplacement drift environment based on the updated thermal loading condition and waste package design. The analysis consists of the following tasks: (1) Identify factors affecting the longevity of ground support materials for use in emplacement drifts; (2) Review existing documents concerning the behavior of candidate ground support materials during the preclosure period; (3) Evaluate impacts of temperature and radiation effects on mechanical and thermal properties of steel. Assess corrosion potential of steel at emplacement drift environment; (4) Evaluate factors affecting longevity of cement grouts for fully grouted rock bolt system. Provide updated information on cement grout mix design for fully grouted rock bolt system; and (5) Evaluate longevity of materials for the emplacement drift invert

Central nervous system promotes thermotolerance via FoxO/DAF-16 activation through octopamine and acetylcholine signaling in Caenorhabditis elegans.

Science.gov (United States)

Furuhashi, Tsubasa; Sakamoto, Kazuichi

2016-03-25

The autonomic nervous system (ANS) responds to many kinds of stressors to maintain homeostasis. Although the ANS is believed to regulate stress tolerance, the exact mechanism underlying this is not well understood. To understand this, we focused on longevity genes, which have functions such as lifespan extension and promotion of stress tolerance. To understand the relationship between ANS and longevity genes, we analyzed stress tolerance of Caenorhabditis elegans treated with octopamine, which has an affinity to noradrenaline in insects, and acetylcholine. Octopamine and acetylcholine did not show resistance against H2O2, but the neurotransmitters promoted thermotolerance via DAF-16. However, chronic treatment with octopamine and acetylcholine did not extend the lifespan, although DAF-16 plays an important role in longevity. In conclusion, our results show that octopamine and acetylcholine activate DAF-16 in response to stress, but chronic induction of octopamine and acetylcholine is not beneficial for increasing longevity. Copyright © 2016 Elsevier Inc. All rights reserved.

78 FR 59219 - Stress Testing of Regulated Entities

Science.gov (United States)

2013-09-26

... institutions. C. Methodologies The Banks requested that Sec. 1238.4 of the rule expressly state that the stress... the scenarios provided by FHFA. FHFA will clarify questions about materiality and about which... its regulated financial institutions. Methodologies and Practices--Sec. 1238.4 Section 1238.4 provides...

Parental divorce and adult longevity.

Science.gov (United States)

Larson, Kandyce; Halfon, Neal

2013-02-01

Life course research has established associations between adverse childhood events and later life health. We examine the relationship of experiencing parental divorce before the age of 16 and survival across 34 years of adulthood. Analysis of panel data from a USA-based survey of 6,928 adults residing in Alameda County, California in 1965. Cox regression was used to examine associations between parental divorce and longevity. Controlling for age, race/ethnicity, gender, and childhood socioeconomic position, respondents who recalled a parental divorce during childhood had increased risk of mortality compared to those with no separation. The association was stronger for premature mortality and deaths due to cardiovascular disease. Divorce in childhood was also associated with lowered adult education, fewer social network ties, more depression, and worse health practices. These factors appeared to explain the association with longevity. Parental divorce in childhood is associated with lowered well-being in adulthood and long-term survival. Early prevention and health promotion efforts may be warranted for children who experience parental divorce or discord as a means of supporting enhanced trajectories of health and well-being.

The significance of translation regulation in the stress response

OpenAIRE

Picard, Flora; Loubière, Pascal; Girbal, Laurence; Bousquet, Muriel

2013-01-01

Background: The stress response in bacteria involves the multistage control of gene expression but is not entirely understood. To identify the translational response of bacteria in stress conditions and assess its contribution to the regulation of gene expression, the translational states of all mRNAs were compared under optimal growth condition and during nutrient (isoleucine) starvation. Results: A genome-scale study of the translational response to nutritional limitation was performed in t...

Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

OpenAIRE

Bao, Ji-Ming; Song, Xian-Lu; Hong, Ying-Qia; Zhu, Hai-Li; Li, Cui; Zhang, Tao; Chen, Wei; Zhao, Shan-Chao; Chen, Qing

2014-01-01

Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence interval...

Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity.

Science.gov (United States)

Panossian, Alexander; Wikman, Georg

2009-09-01

The aim of this review article is to assess the level of scientific evidence presented by clinical trials of adaptogens in fatigue, and to provide a rationale at the molecular level for verified effects. Strong scientific evidence is available for Rhodiola rosea SHR-5 extract, which improved attention, cognitive function and mental performance in fatigue and in chronic fatigue syndrome. Good scientific evidence has been documented in trails in which Schisandra chinensis and Eleutherococcus senticosus increased endurance and mental performance in patients with mild fatigue and weakness. Based on their efficacy in clinical studies, adaptogens can be defined as a pharmacological group of herbal preparations that increase tolerance to mental exhaustion and enhance attention and mental endurance in situations of decreased performance. The beneficial stress-protective effect of adaptogens is related to regulation of homeostasis via several mechanisms of action associated with the hypothalamic-pituitary-adrenal axis and the control of key mediators of stress response such as molecular chaperons (e.g. Hsp70), stress-activated c-Jun N-terminal protein kinase (JNK1), Forkhead Box O transcription factor DAF-16, cortisol and nitric oxide (NO). The key point of action of phytoadaptogens appears to be their up-regulating and stress-mimetic effects on the "stress-sensor" protein Hsp70, which plays an important role in cell survival and apoptosis. Hsp70 inhibits the expression of NO synthase II gene and interacts with glucocorticoid receptors directly and via the JNK pathway, thus affecting the levels of circulating cortisol and NO. Prevention of stress-induced increase in NO, and the associated decrease in ATP production, results in increased performance and endurance. Adaptogen-induced up-regulation of Hsp70 triggers stress-induced JNK-1 and DAF-16-mediated pathways regulating the resistance to stress and resulting in enhanced mental and physical performance and, possibly

Regional Distribution of Longevity Population and Elements in Drinking Water in Jiangjin District, Chongqing City, China.

Science.gov (United States)

Liu, Yonglin; Yuan, Yuyang; Luo, Kunli

2017-10-25

In order to determine the spatial variation of longevity population and elements contained in the drinking water of longevity region in Jiangjin and investigate the relationship between the elements in drinking water and longevity, population censuses on township level and 98 drinking water samples from Jiangjin District, Chongqing City in West China were collected and analyzed. Population statistics on township level showed that the number of centenarians per 100,000 inhabitants (OC), centenarity index (CI), and number of centenarians per 10,000 over 65-year-old subjects (UC) present obvious geographic distribution properties, generally Central region > Northern region > Southern region (Kruskal-Wallis test, p water (150 mg/L water from longevity township (OC > 7.5) in Jiangjin District, whereas soft water (75 mg/L strontium (Sr) (0.73 mg/L) in drinking water from the longevity township was apparently higher than that of non-longevity township (0.44 mg/L) (Mann-Whitney U test, p = 0.019 water from longevity township were also higher than those of non-longevity township (Mann-Whitney U test, p water might be good for the health and prolong people's life.

Life style and longevity among initially healthy middle-aged men: prospective cohort study.

Science.gov (United States)

Heir, Trond; Erikssen, Jan; Sandvik, Leiv

2013-09-11

Few studies have examined how various lifestyle factors in midlife predict longevity, and none of these studies have examined the impact of physical fitness. The present study aimed to examine longevity in relation to smoking, overweight and physical fitness. We prospectively studied longevity (defined as reaching at least 85 years of age) in relation to smoking status, body mass index and physical fitness in 821 healthy men between 51 and 59 years of age. Of these, 369 were smokers, 320 were overweight, and 31 were obese. The associations were adjusted for age, systolic blood pressure and cholesterol level, using multivariate logistic regression analysis. Deaths were registered until the 31st of December, 2006. Physical fitness was measured as the total work performed in a maximal exercise tolerance bicycle test. 252 men survived to the age of 85 years (30.7%). Smoking status was significantly and independently related to longevity; 37.2% of the non-smokers survived to the age of 85, and 22.8% of the smokers. Among non-smokers, overweight and physical fitness were significantly and independently related to longevity after adjustment for age, blood pressure and cholesterol level, but not among smokers. Among non-smokers with high physical fitness, 48.8% reached the age of 85 years, compared to 27.9% among non-smokers with low physical fitness. Lifestyle variables appear to be strong and independent predictors of longevity in initially healthy middle-aged men. The probability of longevity may be a useful concept when informing the general public about the benefits of a healthy lifestyle.

The genetic component of human longevity

DEFF Research Database (Denmark)

Dato, Serena; Thinggaard, Mette Sørensen; De Rango, Francesco

2018-01-01

In human longevity studies, single nucleotide polymorphism (SNP) analysis identified a large number of genetic variants with small effects, yet not easily replicable in different populations. New insights may come from the combined analysis of different SNPs, especially when grouped by metabolic ...

Galactinol as marker for seed longevity

NARCIS (Netherlands)

Souza Vidigal, De D.; Willems, L.A.J.; Arkel, van J.; Dekkers, S.J.W.; Hilhorst, H.W.M.; Bentsink, L.

2016-01-01

Reduced seed longevity or storability is a major problem in seed storage and contributes to increasedcosts in crop production. Here we investigated whether seed galactinol contents could be predictive forseed storability behavior in Arabidopsis, cabbage and tomato. The analyses revealed a positive

Familial longevity is marked by better cognitive performance at middle age: the Leiden Longevity Study.

Directory of Open Access Journals (Sweden)

Marjon Stijntjes

Full Text Available BACKGROUND: Decline in cognitive performance is a highly prevalent health condition in elderly. We studied whether offspring of nonagenarian siblings with a familial history of longevity, perform better on cognitive tests compared to their partners as controls. This is relevant since it could provide insights into determinants underlying decline in cognitive performance. METHODS: Cross-sectional analysis within the longitudinal cohort of the Leiden Longevity Study consisting of middle-aged offspring of nonagenarian siblings together with their partners (n = 500, mean age (SD 66.3 (6.1 and 65.7 (7.2 years, respectively as controls. Memory function, attention and processing speed were tested using the 15-Picture Learning Test, Stroop test and Digit Symbol Substitution Test. Data were analyzed with regression adjusted for age, gender, years of education and additionally for diabetes mellitus, cardiovascular diseases, alcohol use, smoking, inflammatory markers and apolipoprotein E genotype. Robust standard errors were used to account for familial relationships among the offspring. RESULTS: Cognitive performance was worse at higher calendar age (p<0.001, all except Stroop test part 1. The offspring performed better compared to their partners on trial 3 (p = 0.005, the immediate (p = 0.016 and delayed (p = 0.004 recall of the 15-Picture Learning Test as well as on the interference and combined interference score of the Stroop test (p = 0.014 and p = 0.036, respectively in the fully adjusted model. The difference between offspring and partners was estimated to be more than three years according to the observed difference in calendar age. CONCLUSIONS: Offspring of nonagenarian siblings with a familial history of longevity have better cognitive performance compared to the group of their partners of comparable age. This effect is independent of age-related diseases and known possible confounders. Possible explanations might be differences in subclinical

Study on residual stresses in ultrasonic torsional vibration assisted micro-milling

Science.gov (United States)

Lu, Zesheng; Hu, Haijun; Sun, Yazhou; Sun, Qing

2010-10-01

It is well known that machining induced residual stresses can seriously affect the dimensional accuracy, corrosion and wear resistance, etc., and further influence the longevity and reliability of Micro-Optical Components (MOC). In Ultrasonic Torsional Vibration Assisted Micro-milling (UTVAM), cutting parameters, vibration parameters, mill cutter parameters, the status of wear length of tool flank are the main factors which affect residual stresses. A 2D model of UTVAM was established with FE analysis software ABAQUS. Johnson-Cook's flow stress model and shear failure principle are used as the workpiece material model and failure principle, while friction between tool and workpiece uses modified Coulomb's law whose sliding friction area is combined with sticking friction. By means of FEA, the influence rules of cutting parameters, vibration parameters, mill cutter parameters, the status of wear length of tool flank on residual stresses are obtained, which provides a basis for choosing optimal process parameters and improving the longevity and reliability of MOC.

Phenotypic plasticity and longevity in plants and animals: cause and effect?

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Borges, Renee M

2009-10-01

Immobile plants and immobile modular animals outlive unitary animals. This paper discusses competing but not necessarily mutually exclusive theories to explain this extreme longevity, especially from the perspective of phenotypic plasticity. Stem cell immortality, vascular autonomy, and epicormic branching are some important features of the phenotypic plasticity of plants that contribute to their longevity. Monocarpy versus polycarpy can also influence the kind of senescent processes experienced by plants. How density-dependent phenomena affecting the establishment of juveniles in these immobile organisms can influence the evolution of senescence, and consequently longevity, is reviewed and discussed. Whether climate change scenarios will favour long-lived or short-lived organisms, with their attendant levels of plasticity, is also presented.

INVERSION POLYMORPHISM, LONGEVITY, AND BODY SIZE IN A NATURAL POPULATION OF DROSOPHILA BUZZATII.

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Rodriguez, Constantina; Fanara, Juan J; Hasson, Esteban

1999-04-01

In this study we present the results of an analysis of differential longevity associated with Drosophila buzzatii second chromosome inversion karyotypes based on the assessment of more than 1000 individuals collected in a natural population. Comparisons of inversion frequencies between emerged and bait-collected flies showed not only that inversion arrangements were associated with differential longevity, but also that selection was sex specific. Because each individual fly was scored for thorax length and karyotype, we were able to show that longevity selection favoring larger flies coupled with the average effect of inversions on thorax length can account for the change of inversion frequencies due to longevity in females. The observed genotypic-by-sex interaction could be an important mechanism involved in the maintenance of the polymorphism. Arrangement 2Jz 3 , which was shown to impaired fecundity in two independent previous studies, exhibited a positive effect on longevity. This pattern of negative pleiotropy may be another plausible mechanism accounting for the maintenance of the polymorphism. © 1999 The Society for the Study of Evolution.

Personality and Longevity: Knowns, Unknowns, and Implications for Public Health and Personalized Medicine

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Chapman, Benjamin P.; Roberts, Brent; Duberstein, Paul

2011-01-01

We review evidence for links between personality traits and longevity. We provide an overview of personality for health scientists, using the primary organizing framework used in the study of personality and longevity. We then review data on various aspects of personality linked to longevity. In general, there is good evidence that higher level of conscientiousness and lower levels of hostility and Type D or “distressed” personality are associated with greater longevity. Limited evidence suggests that extraversion, openness, perceived control, and low levels of emotional suppression may be associated with longer lifespan. Findings regarding neuroticism are mixed, supporting the notion that many component(s) of neuroticism detract from life expectancy, but some components at some levels may be healthy or protective. Overall, evidence suggests various personality traits are significant predictors of longevity and points to several promising directions for further study. We conclude by discussing the implications of these links for epidemiologic research and personalized medicine and lay out a translational research agenda for integrating the psychology of individual differences into public health and medicine. PMID:21766032

Disrupted amygdala-prefrontal connectivity during emotion regulation links stress-reactive rumination and adolescent depressive symptoms

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Carina H. Fowler

2017-10-01

Full Text Available Rumination in response to stress (stress-reactive rumination has been linked to higher levels of depressive symptoms in adolescents. However, no work to date has examined the neural mechanisms connecting stress-reactive rumination and adolescent depressive symptoms. The present work attempted to bridge this gap through an fMRI study of 41 adolescent girls (Mage = 15.42, SD = 0.33 – a population in whom elevated levels of depressive symptoms, rumination, and social stress sensitivity are displayed. During the scan, participants completed two tasks: an emotion regulation task and a social stress task. Using psychophysiological interaction (PPI analyses, we found that positive functional connectivity between the amygdala and ventrolateral prefrontal cortex (VLPFC during the emotion regulation task mediated the association between stress-reactive rumination and depressive symptoms. These results suggest that stress-reactive rumination may interfere with the expression and development of neural connectivity patterns associated with effective emotion regulation, which may contribute, in turn, to heightened depressive symptoms.

The moderator role of emotion regulation ability in the link between stress and well-being

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Natalio eExtremera

2015-10-01

Full Text Available This article examined the moderating role of a central core dimension of emotional intelligence – emotion-regulation ability – in the relationship between perceived stress and indicators of well-being (depression and subjective happiness in a sample from a community adult population. The relationships for males and females on these dimensions were also compared. Results revealed that emotion-regulation abilities moderated both the association between perceived stress and depression/happiness for the total sample. However, a gender-specific analysis showed that the moderation effect was only significant for males. In short, when males reported a high level of perceived stress, those with high scores in regulating emotions reported higher scores in subjective happiness and lower depression symptoms than those with low regulating emotions. However, no interaction effect of regulating emotions and stress for predicting subjective happiness and depression was found for females. In developing stress management programmes for reducing depression and increasing well-being, these findings suggest that training in emotional regulation may be more beneficial for males than females. Our findings are discussed in terms of the need for future research to understand the different gender associations and to consider these differences in further intervention programmes.

Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

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Stephanie Munk

2017-10-01

Full Text Available The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essential role for SUMOs (small ubiquitin-like modifiers has also been established. Here, we investigate the global interplay between phosphorylation and SUMOylation in response to replication stress. Using SUMO and phosphoproteomic technologies, we identify thousands of regulated modification sites. We find co-regulation of central DNA damage and replication stress responders, of which the ATR-activating factor TOPBP1 is the most highly regulated. Using pharmacological inhibition of the DNA damage response kinases ATR and ATM, we find that these factors regulate global protein SUMOylation in the protein networks that protect DNA upon replication stress and fork breakage, pointing to integration between phosphorylation and SUMOylation in the cellular systems that protect DNA integrity.

Lifestyle and nutrition related to male longevity in Sardinia: an ecological study.

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Pes, G M; Tolu, F; Poulain, M; Errigo, A; Masala, S; Pietrobelli, A; Battistini, N C; Maioli, M

2013-03-01

A demographic analysis in the Mediterranean island of Sardinia revealed marked differences in extreme longevity across the 377 municipalities and particularly identified a mountain inner area where the proportion of oldest subjects among male population has one of the highest validated value worldwide. The cause(s) of this unequal distribution of male longevity may be attributed to a concurrence of environmental, lifestyle and genetic factors. In this study we focussed on some lifestyle and nutrition variables recorded in the island's population in early decades of 20th century, when agricultural and pastoral economy was still prevalent, and try to verify through ecological spatial models if they may account for the variability in male longevity. By computing the Extreme Longevity Index (the proportion of newborns in a given municipality who reach age 100) the island's territory was divided in two areas with relatively higher and lower level of population longevity. Most nutritional variables do not show any significant difference between these two areas whereas a significant difference was found with respect to pastoralism (P = 0.0001), physical activity estimated by the average slope of the territory in each municipality (P = 0.0001), and average daily distance required by the active population to reach the usual workplace (P = 0.0001). Overall, these findings suggest that factors affecting the average energy expenditure of male population such as occupational activity and geographic characteristics of the area where the population mainly resides, are important in explaining the spatial variation of Sardinian extreme longevity. Copyright © 2011 Elsevier B.V. All rights reserved.

Nectarine promotes longevity in Drosophila melanogaster

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Aging is associated with increased oxidative damage and gradual decline of physiology function with age, and is modulated by numerous genetic and environmental factors. Functional fruits are thought to be ideal candidates for promoting longevity and healthspan due to their high contents of polypheno...

Predictors of Exceptional Longevity: Effects of Early-Life Childhood Conditions, Midlife Environment and Parental Characteristics.

Science.gov (United States)

Gavrilov, Leonid A; Gavrilova, Natalia S

Knowledge of strong predictors of mortality and longevity is very important for actuarial science and practice. Earlier studies found that parental characteristics as well as early-life conditions and midlife environment play a significant role in survival to advanced ages. However, little is known about the simultaneous effects of these three factors on longevity. This ongoing study attempts to fill this gap by comparing centenarians born in the United States in 1890-91 with peers born in the same years who died at age 65. The records for centenarians and controls were taken from computerized family histories, which were then linked to 1900 and 1930 U.S. censuses. As a result of this linkage procedure, 765 records of confirmed centenarians and 783 records of controls were obtained. Analysis with multivariate logistic regression found that parental longevity and some midlife characteristics proved to be significant predictors of longevity while the role of childhood conditions was less important. More centenarians were born in the second half of the year compared to controls, suggesting early origins of longevity. We found the existence of both general and gender-specific predictors of human longevity. General predictors common for men and women are paternal and maternal longevity. Gender-specific predictors of male longevity are the farmer occupation at age 40, Northeastern region of birth in the United States and birth in the second half of year. A gender-specific predictor of female longevity is surprisingly the availability of radio in the household according to the 1930 U.S. census. Given the importance of familial longevity as an independent predictor of survival to advanced ages, we conducted a comparative study of biological and nonbiological relatives of centenarians using a larger sample of 1,945 validated U.S. centenarians born in 1880-95. We found that male gender of centenarian has significant positive effect on survival of adult male relatives

Factors affecting on longevity in Northern Khorasan Kordish sheep

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razieh saghi

2016-04-01

Full Text Available Introduction The longevity is normally defined as the length of its productive life in the flock, which is the amount of time an animal spends producing (1. Longevity reflects the ability of ewe to avoid being culled for low production, low fertility, illness and influences the number and cost of replacements required to maintain the flock size. The benefit of increasing longevity are increased average age of the flock, having more ewes available for sale at the end of their four parity, having more ewe lambs to sell, and higher productivity from a slightly older flock age profile (2. Sheep population of Khorasan province (10. In sheep production, longevity has an important influence on the economic returns. Reliable estimates of non genetic effects of longevity are needed to aid establishing an efficient strategy for improving ewe productivity. Thus, the objective of this study was the factors affecting on longevity in Northern Khorasan Kordish sheep. We want to determine effect of environmental and non-genetic factors on longevity. Material and Methods In order to investigate on factors affecting longevity trait in Northen Khorasan Kordish sheep, records of 7469 sheep (187 sire and 2258 dam between 1990 to 2012 that were collected by breeding station of Hossein Abad in Shirvan (This city is located in the north of Mashhad were used. Flock has been kept under village system. Breeding ewes were identified in the data set as those that lambed at 2 year of age and culled at 6 to 7 year of age duo to oldness. Ram kept until a male offspring was available for replacement. In this study longevity was defined as the age of a ewe (in day when it leaves the flock. Ewes were generally removed from the flock due to poor production, low fertility, death and illness. Ewes were identified as being removed from the flock if a lambing record was present at n year of age but not at n+1 years of age. All females were culled before reaching 7 years of age

The genetics of human longevity: an intricacy of genes, environment, culture and microbiome.

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Dato, Serena; Rose, Giuseppina; Crocco, Paolina; Monti, Daniela; Garagnani, Paolo; Franceschi, Claudio; Passarino, Giuseppe

2017-07-01

Approximately one-quarter of the variation in lifespan in developed countries can be attributed to genetic factors. However, even large population based studies investigating genetic influence on human lifespan have been disappointing, identifying only a few genes accounting for genetic susceptibility to longevity. Some environmental and lifestyle determinants associated with longevity have been identified, which interplay with genetic factors in an intricate way. The study of gene-environment and gene-gene interactions can significantly improve our chance to disentangle this complex scenario. In this review, we first describe the most recent approaches for genetic studies of longevity, from those enriched with health parameters and frailty measures to pathway-based and SNP-SNP interaction analyses. Then, we go deeper into the concept of "environmental influences" in human aging and longevity, focusing on the contribution of life style changes, social and cultural influences, as important determinants of survival differences among individuals in a population. Finally, we discuss the contribution of the microbiome in human longevity, as an example of complex interaction between organism and environment. In conclusion, evidences collected from the latest studies on human longevity provide a support for the collection of life-long genetic and environmental/lifestyle variables with beneficial or detrimental effects on health, to improve our understanding of the determinants of human lifespan. Copyright © 2017 Elsevier B.V. All rights reserved.

Family Financial Stress and Adolescent Sexual Risk-Taking: The Role of Self-Regulation.

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Crandall, AliceAnn; Magnusson, Brianna M; Novilla, M Lelinneth B; Novilla, Lynneth Kirsten B; Dyer, W Justin

2017-01-01

The ability to control one's emotions, thoughts, and behaviors is known as self-regulation. Family stress and low adolescent self-regulation have been linked with increased engagement in risky sexual behaviors, which peak in late adolescence and early adulthood. The purpose of this study was to assess whether adolescent self-regulation, measured by parent and adolescent self-report and respiratory sinus arrhythmia, mediates or moderates the relationship between family financial stress and risky sexual behaviors. We assessed these relationships in a 4-year longitudinal sample of 450 adolescents (52 % female; 70 % white) and their parents using structural equation modeling. Results indicated that high family financial stress predicts engagement in risky sexual behaviors as mediated, but not moderated, by adolescent self-regulation. The results suggest that adolescent self-regulatory capacities are a mechanism through which proximal external forces influence adolescent risk-taking. Promoting adolescent self-regulation, especially in the face of external stressors, may be an important method to reduce risk-taking behaviors as adolescents transition to adulthood.

Longevity Candidate Genes and Their Association With Personality Traits in the Elderly

NARCIS (Netherlands)

Luciano, M.; Lopez, L.M.; de Moor, M.H.M.; Harris, S.E.; Davies, G.; Nutile, T.; Krueger, R.F.; Esko, T.; Schlessinger, D.; Toshiko, T.; Derringer, J.; Realo, A.; Hansell, N.K.; Pergadia, M.L.; Pesonen, A.-K.; Sanna, S.; Terracciano, A.; Madden, P.A.F.; Penninx, B.W.J.H.; Spinhoven, Ph.D.; Hartman, C.A.; Oostra, B.A.; Janssens, A.C.J.W.; Eriksson, J.G.; Starr, J.M.; Cannas, A.; Ferrucci, L.; Metspalu, A.; Wright, M.J.; Heath, A.C.; van Duijn, C.M.; Bierut, L.J.; Raikkonen, K.; Martin, N.G.; Ciullo, M.; Rujescu, D.; Boomsma, D.I.; Deary, I.J.

2012-01-01

Human longevity and personality traits are both heritable and are consistently linked at the phenotypic level. We test the hypothesis that candidate genes influencing longevity in lower organisms are associated with variance in the five major dimensions of human personality (measured by the NEO-FFI

Longevity candidate genes and their association with personality traits in the elderly

NARCIS (Netherlands)

Luciano, Michelle; Lopez, Lorna M.; de Moor, Marleen H. M.; Harris, Sarah E.; Davies, Gail; Nutile, Teresa; Krueger, Robert F.; Esko, Tonu; Schlessinger, David; Toshiko, Tanaka; Derringer, Jaime L.; Realo, Anu; Hansell, Narelle K.; Pergadia, Michele L.; Pesonen, Anu-Katriina; Sanna, Serena; Terracciano, Antonio; Madden, Pamela A. F.; Penninx, Brenda; Spinhoven, Philip; Hartman, Catherina A.; Oostra, Ben A.; Janssens, A. Cecile J. W.; Eriksson, Johan G.; Starr, John M.; Cannas, Alessandra; Ferrucci, Luigi; Metspalu, Andres; Wright, Margeret J.; Heath, Andrew C.; van Duijn, Cornelia M.; Bierut, Laura J.; Raikkonen, Katri; Martin, Nicholas G.; Ciullo, Marina; Rujescu, Dan; Boomsma, Dorret I.; Deary, Ian J.

Human longevity and personality traits are both heritable and are consistently linked at the phenotypic level. We test the hypothesis that candidate genes influencing longevity in lower organisms are associated with variance in the five major dimensions of human personality (measured by the NEO-FFI

In Search of Rationality in Human Longevity and Immortality.

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Bhar, Gopal C

2016-01-01

The human body is machine-like, but self-moving, self-regulating, and self-adjusting, governed by willpower and intelligence. Aging of the body is basically a maintenance problem and so it could perhaps be postponed by thorough and frequent maintenance. Aging brings on a cascade of ills and health problems leading to deterioration of physical, mental, emotional, and social dimensions of life. This paper deals with solution of the problem philosophically in the light of Indian scriptures without entering into traditional bioethical issues. With a meaningful reason for existence, life can be extended. Examining the scientific perspectives on aging, some common manipulations for its extension are discussed. These are calorie restriction, vitamin and antioxidant treatment, exercise and hormonal interventions, etc. Finally, the question of longevity is explored through pursuance of eternal value-based activity and spirituality in the tradition of Indian heritage.

Changes in Teacher Stress through Participation in Pre-Referral Intervention Teams

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Lhospital, Ann Shargo; Gregory, Anne

2009-01-01

Teachers today face high stress that can compromise their well-being, longevity in the profession, and the quality of their interactions with students. Pre-referral interventions, which address individual student difficulties before consideration for special education, may help buffer teacher stress through student interventions and team support.…

Genetics of longevity. data from the studies on Sicilian centenarians

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Balistreri Carmela R

2012-04-01

Full Text Available Abstract The demographic and social changes of the past decades have determined improvements in public health and longevity. So, the number of centenarians is increasing as a worldwide phenomenon. Scientists have focused their attention on centenarians as optimal model to address the biological mechanisms of "successful and unsuccessful ageing". They are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases, such as cardiovascular diseases and cancer. Thus, particular attention has been centered on their genetic background and immune system. In this review, we report our data gathered for over 10 years in Sicilian centenarians. Based on results obtained, we suggest longevity as the result of an optimal performance of immune system and an over-expression of anti-inflammatory sequence variants of immune/inflammatory genes. However, as well known, genetic, epigenetic, stochastic and environmental factors seem to have a crucial role in ageing and longevity. Epigenetics is associated with ageing, as demonstrated in many studies. In particular, ageing is associated with a global loss of methylation state. Thus, the aim of future studies will be to analyze the weight of epigenetic changes in ageing and longevity.

Battery longevity in cardiac resynchronization therapy implantable cardioverter defibrillators.

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Alam, Mian Bilal; Munir, Muhammad Bilal; Rattan, Rohit; Flanigan, Susan; Adelstein, Evan; Jain, Sandeep; Saba, Samir

2014-02-01

Cardiac resynchronization therapy (CRT) implantable cardioverter defibrillators (ICDs) deliver high burden ventricular pacing to heart failure patients, which has a significant effect on battery longevity. The aim of this study was to investigate whether battery longevity is comparable for CRT-ICDs from different manufacturers in a contemporary cohort of patients. All the CRT-ICDs implanted at our institution from 1 January 2008 to 31 December 2010 were included in this analysis. Baseline demographic and clinical data were collected on all patients using the electronic medical record. Detailed device information was collected on all patients from scanned device printouts obtained during routine follow-up. The primary endpoint was device replacement for battery reaching the elective replacement indicator (ERI). A total of 646 patients (age 69 ± 13 years), implanted with CRT-ICDs (Boston Scientific 173, Medtronic 416, and St Jude Medical 57) were included in this analysis. During 2.7 ± 1.5 years follow-up, 113 (17%) devices had reached ERI (Boston scientific 4%, Medtronic 25%, and St Jude Medical 7%, P battery was significantly worse for Medtronic devices compared with devices from other manufacturers (94% for Boston scientific, 67% for Medtronic, and 92% for St Jude Medical, P battery longevity by manufacturer was independent of pacing burden, lead parameters, and burden of ICD therapy. There are significant discrepancies in CRT-ICD battery longevity by manufacturer. These data have important implications on clinical practice and patient outcomes.

The relative tail of longevity and the mean remaining lifetime

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James W. Vaupel

2006-02-01

Full Text Available Vaupel (1998 posed the provocative question, "When it comes to death, how do people and flies differ from Toyotas?" He suggested that as the force of natural selection diminishes with age, structural reliability concepts can be profitably used in mortality analysis. Vaupel (2003 went a step further, using simulations to investigate the impact of redundancy, repair capacity, and heterogeneity on the relative length of post-reproductive life spans, called relative tails of longevity. His 2003 paper showed that structural redundancy and the possibility of repair decrease the relative tail of longevity, whereas greater heterogeneity increases it. Here, we consider the problem in much greater generality and prove these results analytically. Structures with repairable and non-repairable components are considered. Heterogeneity is described by a frailty-type model and different definitions of the tail of longevity are discussed.

A novel generalized normal distribution for human longevity and other negatively skewed data.

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Robertson, Henry T; Allison, David B

2012-01-01

Negatively skewed data arise occasionally in statistical practice; perhaps the most familiar example is the distribution of human longevity. Although other generalizations of the normal distribution exist, we demonstrate a new alternative that apparently fits human longevity data better. We propose an alternative approach of a normal distribution whose scale parameter is conditioned on attained age. This approach is consistent with previous findings that longevity conditioned on survival to the modal age behaves like a normal distribution. We derive such a distribution and demonstrate its accuracy in modeling human longevity data from life tables. The new distribution is characterized by 1. An intuitively straightforward genesis; 2. Closed forms for the pdf, cdf, mode, quantile, and hazard functions; and 3. Accessibility to non-statisticians, based on its close relationship to the normal distribution.

Effect of floral bud reduction on flower longevity in Asiatic hybrids lilies.

NARCIS (Netherlands)

Meulen-Muisers, van der J.J.M.; Oeveren, van J.C.; Sandbrink, J.M.; Tuyl, van J.M.

1995-01-01

Floral bud abortion was found to be an undesirable source of non-genetic variation in breeding trials directed on the improvement of individual flower longevity in Asiatic hybrid lilies. It increased the longevity of the remaining flowers of the inflorescence. A similar response was found after

Silicon Regulates Potential Genes Involved in Major Physiological Processes in Plants to Combat Stress

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Abinaya Manivannan

2017-08-01

Full Text Available Silicon (Si, the quasi-essential element occurs as the second most abundant element in the earth's crust. Biological importance of Si in plant kingdom has become inevitable particularly under stressed environment. In general, plants are classified as high, medium, and low silicon accumulators based on the ability of roots to absorb Si. The uptake of Si directly influence the positive effects attributed to the plant but Si supplementation proves to mitigate stress and recover plant growth even in low accumulating plants like tomato. The application of Si in soil as well as soil-less cultivation systems have resulted in the enhancement of quantitative and qualitative traits of plants even under stressed environment. Silicon possesses several mechanisms to regulate the physiological, biochemical, and antioxidant metabolism in plants to combat abiotic and biotic stresses. Nevertheless, very few reports are available on the aspect of Si-mediated molecular regulation of genes with potential role in stress tolerance. The recent advancements in the era of genomics and transcriptomics have opened an avenue for the determination of molecular rationale associated with the Si amendment to the stress alleviation in plants. Therefore, the present endeavor has attempted to describe the recent discoveries related to the regulation of vital genes involved in photosynthesis, transcription regulation, defense, water transport, polyamine synthesis, and housekeeping genes during abiotic and biotic stress alleviation by Si. Furthermore, an overview of Si-mediated modulation of multiple genes involved in stress response pathways such as phenylpropanoid pathway, jasmonic acid pathway, ABA-dependent or independent regulatory pathway have been discussed in this review.

Self-Regulation and Economic Stress in Children of Hispanic Immigrants and Their Peers: Better Regulation at a Cost?

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McFadyen-Ketchum, Lisa Schlueter; Hurwich-Reiss, Eliana; Stiles, Allison A.; Mendoza, Marina M.; Badanes, Lisa S.; Dmitrieva, Julia; Watamura, Sarah Enos

2016-01-01

Research Findings: Although there is a well-established relationship between economic stress and children's self-regulation, few studies have examined this relationship in children of Hispanic immigrants (COHIs), a rapidly growing population. In a sample of preschool children (N = 165), we examined whether economic stress predicted teacher…

Mild heat stress at a young age in Drosophila melanogaster leads to ...

Indian Academy of Sciences (India)

Unknown

effect on stress resistance later in life, and on longevity. ... bouts of mild heat stress (3 h at 34°C) at a young age (days 2, 4 and 6 post-eclosion) or held under .... The mortality during the investigated lifespan .... at least during early senescence.

Dynamic regulation of NMDAR function in the adult brain by the stress hormone corticosterone

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Yiu Chung eTse

2012-03-01

Full Text Available Stress and corticosteroids dynamically modulate the expression of synaptic plasticity at glutamatergic synapses in the developed brain. Together with alpha-amino-3-hydroxy-methyl-4-isoxazole propionic acid receptors (AMPAR, N-methyl-D-aspartate receptors (NMDAR are critical mediators of synaptic function and are essential for the induction of many forms of synaptic plasticity. Regulation of NMDAR function by cortisol/corticosterone (CORT may be fundamental to the effects of stress on synaptic plasticity. Recent reports of the efficacy of NMDAR antagonists in treating certain stress-associated psychopathologies further highlight the importance of understanding the regulation of NMDAR function by CORT. Knowledge of how corticosteroids regulate NMDAR function within the adult brain is relatively sparse, perhaps due to a common belief that NMDAR function is relatively stable in the adult brain. We review recent results from our laboratory and others demonstrating dynamic regulation of NMDAR function by CORT in the adult brain. In addition, we consider the issue of how differences in the early life environment may program differential sensitivity to modulation of NMDAR function by CORT and how this may influence synaptic function during stress. Findings from these studies demonstrate that NMDAR function in the adult hippocampus remains sensitive to even brief exposures to CORT and that the capacity for modulation of NMDAR may be programmed, in part, by the early life environment. Modulation of NMDAR function may contribute to dynamic regulation of synaptic plasticity and adaptation in the face of stress, however enhanced NMDAR function may be implicated in mechanisms of stress related psychopathologies including depression.

Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study.

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Anselmi, Chiara Viviani; Malovini, Alberto; Roncarati, Roberta; Novelli, Valeria; Villa, Francesco; Condorelli, Gianluigi; Bellazzi, Riccardo; Puca, Annibale Alessandro

2009-04-01

A number of potential candidate genes in a variety of biological pathways have been associated with longevity in model organisms. Many of these genes have human homologs and thus have the potential to provide insights into human longevity. Recently, several studies suggested that FOXO3A functions as a key bridge for various signaling pathways that influence aging and longevity. Interestingly, Willcox and colleagues identified several variants that displayed significant genotype-gender interaction in male human longevity. In particular, a nested case-control study was performed in an ethnic Japanese population in Hawaii, and five candidate longevity genes were chosen based on links to the insulin-insulin-like growth factor-1 (IGF-1) signaling pathway. In the Willcox study, the investigated genetic variations (rs2802292, rs2764264, and rs13217795) within the FOXO3A gene were significantly associated with longevity in male centenarians. We validated the association of FOXO3A polymorphisms with extreme longevity in males from the Southern Italian Centenarian Study. Particularly, rs2802288, a proxy of rs2802292, showed the best allelic association--minor allele frequency (MAF) = 0.49; p = 0.003; odds ratio (OR) = 1.51; 95% confidence interval (CI), 1.15-1.98). Furthermore, we undertook a meta-analysis to explore the significance of rs2802292 association with longevity by combining the association results of the current study and the findings coming from the Willcox et al. investigation. Our data point to a key role of FOXO3A in human longevity and confirm the feasibility of the identification of such genes with centenarian-controls studies. Moreover, we hypothesize the susceptibility to the longevity phenotype may well be the result of complex interactions involving genes and environmental factors but also gender.

Transcriptome analysis uncovers Arabidopsis F-BOX STRESS INDUCED 1 as a regulator of jasmonic acid and abscisic acid stress gene expression.

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Gonzalez, Lauren E; Keller, Kristen; Chan, Karen X; Gessel, Megan M; Thines, Bryan C

2017-07-17

The ubiquitin 26S proteasome system (UPS) selectively degrades cellular proteins, which results in physiological changes to eukaryotic cells. F-box proteins are substrate adaptors within the UPS and are responsible for the diversity of potential protein targets. Plant genomes are enriched in F-box genes, but the vast majority of these have unknown roles. This work investigated the Arabidopsis F-box gene F-BOX STRESS INDUCED 1 (FBS1) for its effects on gene expression in order elucidate its previously unknown biological function. Using publically available Affymetrix ATH1 microarray data, we show that FBS1 is significantly co-expressed in abiotic stresses with other well-characterized stress response genes, including important stress-related transcriptional regulators. This gene suite is most highly expressed in roots under cold and salt stresses. Transcriptome analysis of fbs1-1 knock-out plants grown at a chilling temperature shows that hundreds of genes require FBS1 for appropriate expression, and that these genes are enriched in those having roles in both abiotic and biotic stress responses. Based on both this genome-wide expression data set and quantitative real-time PCR (qPCR) analysis, it is apparent that FBS1 is required for elevated expression of many jasmonic acid (JA) genes that have established roles in combatting environmental stresses, and that it also controls a subset of JA biosynthesis genes. FBS1 also significantly impacts abscisic acid (ABA) regulated genes, but this interaction is more complex, as FBS1 has both positive and negative effects on ABA-inducible and ABA-repressible gene modules. One noteworthy effect of FBS1 on ABA-related stress processes, however, is the restraint it imposes on the expression of multiple class I LIPID TRANSFER PROTEIN (LTP) gene family members that have demonstrated protective effects in water deficit-related stresses. FBS1 impacts plant stress responses by regulating hundreds of genes that respond to the plant

Quantitative trait loci associated with longevity of lettuce seeds under conventional and controlled deterioration storage conditions.

Science.gov (United States)

Schwember, Andrés R; Bradford, Kent J

2010-10-01

Lettuce (Lactuca sativa L.) seeds have poor shelf life and exhibit thermoinhibition (fail to germinate) above ∼25°C. Seed priming (controlled hydration followed by drying) alleviates thermoinhibition by increasing the maximum germination temperature, but reduces lettuce seed longevity. Controlled deterioration (CD) or accelerated ageing storage conditions (i.e. elevated temperature and relative humidity) are used to study seed longevity and to predict potential seed lifetimes under conventional storage conditions. Seeds produced in 2002 and 2006 of a recombinant inbred line (RIL) population derived from a cross between L. sativa cv. Salinas×L. serriola accession UC96US23 were utilized to identify quantitative trait loci (QTLs) associated with seed longevity under CD and conventional storage conditions. Multiple longevity-associated QTLs were identified under both conventional and CD storage conditions for control (non-primed) and primed seeds. However, seed longevity was poorly correlated between the two storage conditions, suggesting that deterioration processes under CD conditions are not predictive of ageing in conventional storage conditions. Additionally, the same QTLs were not identified when RIL populations were grown in different years, indicating that lettuce seed longevity is strongly affected by production environment. Nonetheless, a major QTL on chromosome 4 [Seed longevity 4.1 (Slg4.1)] was responsible for almost 23% of the phenotypic variation in viability of the conventionally stored control seeds of the 2006 RIL population, with improved longevity conferred by the Salinas allele. QTL analyses may enable identification of mechanisms responsible for the sensitivity of primed seeds to CD conditions and breeding for improved seed longevity.

Ambient intelligence might support increased longevity.

Science.gov (United States)

Noury, Norbert

2014-01-01

Several technologies entered our homes to change our lives. First electricity brought light and comfort, now communication technologies are transforming our living place into a connected place allowing new services to be invented, comfort, security, wellness and health services. The ICTs in homes can now help prolonge our longevity.

Abiotic stress responses in plants: roles of calmodulin-regulated proteins

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Virdi, Amardeep S.; Singh, Supreet; Singh, Prabhjeet

2015-01-01

Intracellular changes in calcium ions (Ca2+) in response to different biotic and abiotic stimuli are detected by various sensor proteins in the plant cell. Calmodulin (CaM) is one of the most extensively studied Ca2+-sensing proteins and has been shown to be involved in transduction of Ca2+ signals. After interacting with Ca2+, CaM undergoes conformational change and influences the activities of a diverse range of CaM-binding proteins. A number of CaM-binding proteins have also been implicated in stress responses in plants, highlighting the central role played by CaM in adaptation to adverse environmental conditions. Stress adaptation in plants is a highly complex and multigenic response. Identification and characterization of CaM-modulated proteins in relation to different abiotic stresses could, therefore, prove to be essential for a deeper understanding of the molecular mechanisms involved in abiotic stress tolerance in plants. Various studies have revealed involvement of CaM in regulation of metal ions uptake, generation of reactive oxygen species and modulation of transcription factors such as CAMTA3, GTL1, and WRKY39. Activities of several kinases and phosphatases have also been shown to be modulated by CaM, thus providing further versatility to stress-associated signal transduction pathways. The results obtained from contemporary studies are consistent with the proposed role of CaM as an integrator of different stress signaling pathways, which allows plants to maintain homeostasis between different cellular processes. In this review, we have attempted to present the current state of understanding of the role of CaM in modulating different stress-regulated proteins and its implications in augmenting abiotic stress tolerance in plants. PMID:26528296

Dicarbonyl stress and glyoxalase enzyme system regulation in human skeletal muscle.

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Mey, Jacob T; Blackburn, Brian K; Miranda, Edwin R; Chaves, Alec B; Briller, Joan; Bonini, Marcelo G; Haus, Jacob M

2018-02-01

Skeletal muscle insulin resistance is a hallmark of Type 2 diabetes (T2DM) and may be exacerbated by protein modifications by methylglyoxal (MG), known as dicarbonyl stress. The glyoxalase enzyme system composed of glyoxalase 1/2 (GLO1/GLO2) is the natural defense against dicarbonyl stress, yet its protein expression, activity, and regulation remain largely unexplored in skeletal muscle. Therefore, this study investigated dicarbonyl stress and the glyoxalase enzyme system in the skeletal muscle of subjects with T2DM (age: 56 ± 5 yr.; BMI: 32 ± 2 kg/m 2 ) compared with lean healthy control subjects (LHC; age: 27 ± 1 yr.; BMI: 22 ± 1 kg/m 2 ). Skeletal muscle biopsies obtained from the vastus lateralis at basal and insulin-stimulated states of the hyperinsulinemic (40 mU·m -2 ·min -1 )-euglycemic (5 mM) clamp were analyzed for proteins related to dicarbonyl stress and glyoxalase biology. At baseline, T2DM had increased carbonyl stress and lower GLO1 protein expression (-78.8%), which inversely correlated with BMI, percent body fat, and HOMA-IR, while positively correlating with clamp-derived glucose disposal rates. T2DM also had lower NRF2 protein expression (-31.6%), which is a positive regulator of GLO1, while Keap1 protein expression, a negative regulator of GLO1, was elevated (207%). Additionally, insulin stimulation during the clamp had a differential effect on NRF2, Keap1, and MG-modified protein expression. These data suggest that dicarbonyl stress and the glyoxalase enzyme system are dysregulated in T2DM skeletal muscle and may underlie skeletal muscle insulin resistance. Whether these phenotypic differences contribute to the development of T2DM warrants further investigation.

Variance in centrality within rock hyrax social networks predicts adult longevity.

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Adi Barocas

Full Text Available BACKGROUND: In communal mammals the levels of social interaction among group members vary considerably. In recent years, biologists have realized that within-group interactions may affect survival of the group members. Several recent studies have demonstrated that the social integration of adult females is positively associated with infant survival, and female longevity is affected by the strength and stability of the individual social bonds. Our aim was to determine the social factors that influence adult longevity in social mammals. METHODOLOGY/PRINCIPAL FINDINGS: As a model system, we studied the social rock hyrax (Procavia capensis, a plural breeder with low reproductive skew, whose groups are mainly composed of females. We applied network theory using 11 years of behavioral data to quantify the centrality of individuals within groups, and found adult longevity to be inversely correlated to the variance in centrality. In other words, animals in groups with more equal associations lived longer. Individual centrality was not correlated with longevity, implying that social tension may affect all group members and not only the weakest or less connected ones. CONCLUSIONS/SIGNIFICANCE: Our novel findings support previous studies emphasizing the adaptive value of social associations and the consequences of inequality among adults within social groups. However, contrary to previous studies, we suggest that it is not the number or strength of associations that an adult individual has (i.e. centrality that is important, but the overall configuration of social relationships within the group (i.e. centrality SD that is a key factor in influencing longevity.

Relationship between cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers: Exploring multiple mediation model.

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Cai, Wen-Peng; Pan, Yu; Zhang, Shui-Miao; Wei, Cun; Dong, Wei; Deng, Guang-Hui

2017-10-01

The current study aimed to explore the association of cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers and to understand the multiple mediation effects of social support and resilience on the relationship between cognitive emotion regulation and acute stress responses. A total of 1477 male soldiers completed mental scales, including the cognitive emotion regulation questionnaire-Chinese version, the perceived social support scale, the Chinese version of the Connor-Davidson resilience scale, and the military acute stress scale. As hypothesized, physiological responses, psychological responses, and acute stress were associated with negative-focused cognitive emotion regulation, and negatively associated with positive-focused cognitive emotion regulation, social supports and resilience. Besides, positive-focused cognitive emotion regulation, social support, and resilience were significantly associated with one another, and negative-focused cognitive emotion regulation was negatively associated with social support. Regression analysis and bootstrap analysis showed that social support and resilience had partly mediating effects on negative strategies and acute stress, and fully mediating effects on positive strategies and acute stress. These results thus indicate that military acute stress is significantly associated with cognitive emotion regulation, social support, and resilience, and that social support and resilience have multiple mediation effects on the relationship between cognitive emotion regulation and acute stress responses. Copyright © 2017 Elsevier B.V. All rights reserved.

TATN-1 mutations reveal a novel role for tyrosine as a metabolic signal that influences developmental decisions and longevity in Caenorhabditis elegans.

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Annabel A Ferguson

Full Text Available Recent work has identified changes in the metabolism of the aromatic amino acid tyrosine as a risk factor for diabetes and a contributor to the development of liver cancer. While these findings could suggest a role for tyrosine as a direct regulator of the behavior of cells and tissues, evidence for this model is currently lacking. Through the use of RNAi and genetic mutants, we identify tatn-1, which is the worm ortholog of tyrosine aminotransferase and catalyzes the first step of the conserved tyrosine degradation pathway, as a novel regulator of the dauer decision and modulator of the daf-2 insulin/IGF-1-like (IGFR signaling pathway in Caenorhabditis elegans. Mutations affecting tatn-1 elevate tyrosine levels in the animal, and enhance the effects of mutations in genes that lie within the daf-2/insulin signaling pathway or are otherwise upstream of daf-16/FOXO on both dauer formation and worm longevity. These effects are mediated by elevated tyrosine levels as supplemental dietary tyrosine mimics the phenotypes produced by a tatn-1 mutation, and the effects still occur when the enzymes needed to convert tyrosine into catecholamine neurotransmitters are missing. The effects on dauer formation and lifespan require the aak-2/AMPK gene, and tatn-1 mutations increase phospho-AAK-2 levels. In contrast, the daf-16/FOXO transcription factor is only partially required for the effects on dauer formation and not required for increased longevity. We also find that the controlled metabolism of tyrosine by tatn-1 may function normally in dauer formation because the expression of the TATN-1 protein is regulated both by daf-2/IGFR signaling and also by the same dietary and environmental cues which influence dauer formation. Our findings point to a novel role for tyrosine as a developmental regulator and modulator of longevity, and support a model where elevated tyrosine levels play a causal role in the development of diabetes and cancer in people.

TATN-1 Mutations Reveal a Novel Role for Tyrosine as a Metabolic Signal That Influences Developmental Decisions and Longevity in Caenorhabditis elegans

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Ferguson, Annabel A.; Dumas, Kathleen J.; Ritov, Vladimir B.; Matern, Dietrich; Hu, Patrick J.; Fisher, Alfred L.

2013-01-01

Recent work has identified changes in the metabolism of the aromatic amino acid tyrosine as a risk factor for diabetes and a contributor to the development of liver cancer. While these findings could suggest a role for tyrosine as a direct regulator of the behavior of cells and tissues, evidence for this model is currently lacking. Through the use of RNAi and genetic mutants, we identify tatn-1, which is the worm ortholog of tyrosine aminotransferase and catalyzes the first step of the conserved tyrosine degradation pathway, as a novel regulator of the dauer decision and modulator of the daf-2 insulin/IGF-1-like (IGFR) signaling pathway in Caenorhabditis elegans. Mutations affecting tatn-1 elevate tyrosine levels in the animal, and enhance the effects of mutations in genes that lie within the daf-2/insulin signaling pathway or are otherwise upstream of daf-16/FOXO on both dauer formation and worm longevity. These effects are mediated by elevated tyrosine levels as supplemental dietary tyrosine mimics the phenotypes produced by a tatn-1 mutation, and the effects still occur when the enzymes needed to convert tyrosine into catecholamine neurotransmitters are missing. The effects on dauer formation and lifespan require the aak-2/AMPK gene, and tatn-1 mutations increase phospho-AAK-2 levels. In contrast, the daf-16/FOXO transcription factor is only partially required for the effects on dauer formation and not required for increased longevity. We also find that the controlled metabolism of tyrosine by tatn-1 may function normally in dauer formation because the expression of the TATN-1 protein is regulated both by daf-2/IGFR signaling and also by the same dietary and environmental cues which influence dauer formation. Our findings point to a novel role for tyrosine as a developmental regulator and modulator of longevity, and support a model where elevated tyrosine levels play a causal role in the development of diabetes and cancer in people. PMID:24385923

Longevity and Depreciation of Audiovisual Equipment.

Science.gov (United States)

Post, Richard

1987-01-01

Describes results of survey of media service directors at public universities in Ohio to determine the expected longevity of audiovisual equipment. Use of the Delphi technique for estimates is explained, results are compared with an earlier survey done in 1977, and use of spreadsheet software to calculate depreciation is discussed. (LRW)

Mother-Infant Emotion Regulation at Three Months: The Role of Maternal Anxiety, Depression and Parenting Stress.

Science.gov (United States)

Riva Crugnola, Cristina; Ierardi, Elena; Ferro, Valentino; Gallucci, Marcello; Parodi, Cinzia; Astengo, Marina

While the association between anxiety and postpartum depression is well known, few studies have investigated the relationship between these two states and parenting stress. Furthermore, a number of studies have found that postpartum depression affects mother-infant emotion regulation, but there has been only one study on anxiety and emotion regulation and no studies at all on parenting stress and emotion regulation. Therefore, the primary aim of our study is to identify, in a community sample of 71 mothers, the relationship between maternal depression, anxiety, and parenting stress. The second aim is to examine the relationship between anxiety, postpartum depression, and parenting stress and mother-infant emotion regulation assessed at 3 months. Mother-infant interaction was coded with a modified version of the Infant Caregiver and Engagement Phases (ICEP) using a microanalytic approach. The Edinburgh Postnatal Depression Scale (EPDS), State-Trait Anxiety Inventory (STAI), and Parenting Stress Index-Short Form (PSI-SF) were administered to the mothers to assess depression, anxiety, and parenting stress, respectively. Analysis revealed correlations between anxiety and depression, showing that parenting stress is associated with both states. In a laboratory observation, depression was correlated with both negative maternal states and negative dyadic matches as well as infant positive/mother negative mismatches; anxiety was correlated with both negative maternal states and infant negative states as well as mismatches involving one of the partners having a negative state. Multiple regression analysis showed that anxiety is a greater predictor than depression of less adequate styles of mother-infant emotion regulation. Parenting stress was not shown to predict such regulation. © 2016 S. Karger AG, Basel.

Evolutionary history and stress regulation of the lectin superfamily in higher plants

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Ramachandran Srinivasan

2010-03-01

Full Text Available Abstract Background Lectins are a class of carbohydrate-binding proteins. They play roles in various biological processes. However, little is known about their evolutionary history and their functions in plant stress regulation. The availability of full genome sequences from various plant species makes it possible to perform a whole-genome exploration for further understanding their biological functions. Results Higher plant genomes encode large numbers of lectin proteins. Based on their domain structures and phylogenetic analyses, a new classification system has been proposed. In this system, 12 different families have been classified and four of them consist of recently identified plant lectin members. Further analyses show that some of lectin families exhibit species-specific expansion and rapid birth-and-death evolution. Tandem and segmental duplications have been regarded as the major mechanisms to drive lectin expansion although retrogenes also significantly contributed to the birth of new lectin genes in soybean and rice. Evidence shows that lectin genes have been involved in biotic/abiotic stress regulations and tandem/segmental duplications may be regarded as drivers for plants to adapt various environmental stresses through duplication followed by expression divergence. Each member of this gene superfamily may play specialized roles in a specific stress condition and function as a regulator of various environmental factors such as cold, drought and high salinity as well as biotic stresses. Conclusions Our studies provide a new outline of the plant lectin gene superfamily and advance the understanding of plant lectin genes in lineage-specific expansion and their functions in biotic/abiotic stress-related developmental processes.

The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

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Justin W Walley

2008-12-01

Full Text Available Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD is required for the expression of selected genes downstream of the jasmonate (JA and ethylene (ET signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

A matrix approach to the statistics of longevity in heterogeneous frailty models

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Hal Caswell

2014-09-01

Full Text Available Background: The gamma-Gompertz model is a fixed frailty model in which baseline mortality increasesexponentially with age, frailty has a proportional effect on mortality, and frailty at birth follows a gamma distribution. Mortality selects against the more frail, so the marginal mortality rate decelerates, eventually reaching an asymptote. The gamma-Gompertz is one of a wider class of frailty models, characterized by the choice of baseline mortality, effects of frailty, distributions of frailty, and assumptions about the dynamics of frailty. Objective: To develop a matrix model to compute all the statistical properties of longevity from thegamma-Gompertz and related models. Methods: I use the vec-permutation matrix formulation to develop a model in which individuals are jointly classified by age and frailty. The matrix is used to project the age and frailty dynamicsof a cohort and the fundamental matrix is used to obtain the statistics of longevity. Results: The model permits calculation of the mean, variance, coefficient of variation, skewness and all moments of longevity, the marginal mortality and survivorship functions, the dynamics of the frailty distribution, and other quantities. The matrix formulation extends naturally to other frailty models. I apply the analysis to the gamma-Gompertz model (for humans and laboratory animals, the gamma-Makeham model, and the gamma-Siler model, and to a hypothetical dynamic frailty model characterized by diffusion of frailty with reflecting boundaries.The matrix model permits partitioning the variance in longevity into components due to heterogeneity and to individual stochasticity. In several published human data sets, heterogeneity accounts for less than 10Š of the variance in longevity. In laboratory populations of five invertebrate animal species, heterogeneity accounts for 46Š to 83Š ofthe total variance in longevity.

Exploring the genetics of longevity in the Old Order Amish.

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Sorkin, John; Post, Wendy; Pollin, Toni I; O'Connell, Jeffrey R; Mitchell, Braxton D; Shuldiner, Alan R

2005-02-01

Lifespan is a complex phenotype determined by the interaction of genetic and environmental factors. This makes the identification of variants in genes that influence longevity challenging. We believe that the Old Order Amish (OOA) of Lancaster, Pennsylvania is an excellent population for studying the genetics of longevity. They are a closed population derived from a limited number of founders. They have large families and maintain extensive genealogic records dating to the 1700 s. They eschew modern technology; their lifestyle is little changed over the last 250 years. Homogeneity of environment and lifestyle factors across time and across the OOA population minimizes the influence that environmental factors have in determining the differences in lifespan between individuals. We hypothesize that this reduction in environmental variability will make it easier to identify the genetic factors that influence lifespan. In this article, we describe our strategy for identifying variants in genes that influence longevity in the Amish and present the results of our studies to date.

AB126. Association between FOX03A gene polymorphisms and human longevity: a meta-analysis

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Zhao, Shanchao; Bao, Jiming; Song, Xianlu

2016-01-01

Objective Numerous studies have shown associations between the FOX03A gene, encoding the forkhead box 03 transcription factor, and human or specifically male longevity. However, the associations of specific FOX03A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. Methods A comprehensive search was conducted to identify studies of FOX03A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (Cls) were calculated by comparing the minor and major alleles. Results A total of seven articles reporting associations of FOX03A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rsI3217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR =1.36, 95% CI, 1. 10–1.69, P=0.005; OR =1.20, 95% CI, 1.04–1.37, P=0.01; OR =1.27, 95% CI, 1.10–1.46, P=0.001; OR =1.14, 95% CI, 1.01–1.27 and OR =1.24, 95% CI, 1.07–1.43, P=0.003, respectively). Analysis is stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR =1.54, 95% CI, 1.33–1.79, P<0.001; OR =1.38, 95% CI, 1.15–1.66, P=0.001; and OR =1.39, 95% CI, 1.15–1.67, P=0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. Conclusions In conclusion, this meta-analysis indicates a significant association of five FOX03A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

The naked mole-rat response to oxidative stress: just deal with it.

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Lewis, Kaitlyn N; Andziak, Blazej; Yang, Ting; Buffenstein, Rochelle

2013-10-20

The oxidative stress theory of aging has been the most widely accepted theory of aging providing insights into why we age and die for over 50 years, despite mounting evidence from a multitude of species indicating that there is no direct relationship between reactive oxygen species (ROS) and longevity. Here we explore how different species, including the longest lived rodent, the naked mole-rat, have defied the most predominant aging theory. In the case of extremely long-lived naked mole-rat, levels of ROS production are found to be similar to mice, antioxidant defenses unexceptional, and even under constitutive conditions, naked mole-rats combine a pro-oxidant intracellular milieu with high, steady state levels of oxidative damage. Clearly, naked mole-rats can tolerate this level of oxidative stress and must have mechanisms in place to prevent its translation into potentially lethal diseases. In addition to the naked mole-rat, other species from across the phylogenetic spectrum and even certain mouse strains do not support this theory. Moreover, overexpressing or knocking down antioxidant levels alters levels of oxidative damage and even cancer incidence, but does not modulate lifespan. Perhaps, it is not oxidative stress that modulates healthspan and longevity, but other cytoprotective mechanisms that allow animals to deal with high levels of oxidative damage and stress, and nevertheless live long, relatively healthy lifespans. Studying these mechanisms in uniquely long-lived species, like the naked mole-rat, may help us tease out the key contributors to aging and longevity.

Understanding the Posttranscriptional Regulation of Plant Responses to Abiotic Stress

KAUST Repository

AlShareef, Sahar A.

2017-06-01

Constitutive and alternative splicing of pre-mRNAs from multiexonic genes controls the diversity of the proteome; these precisely regulated processes also fine-tune responses to cues related to growth, development, and biotic and abiotic stresses. Recent work showed that AS is pervasive across plant species, with more than 60% of intron-containing genes producing different isoforms. Mammalian cell-based assays have discovered various AS small-molecule inhibitors that perturb splicing and thereby provide invaluable tools for use as chemical probes to uncover the molecular underpinnings of splicing regulation and as potential anticancer compounds. Here, I show that the macrolide Pladienolide B (PB) and herboxidiene (GEX1A) inhibits both constitutive and alternative splicing, mimics an abiotic stress signal, and activates the abscisic acid (ABA) pathway in plants. Moreover, PB and GEX1A activate genome-wide transcriptional patterns involved in abiotic stress responses in plants. PB and GEX1A treatment triggered the ABA signaling pathway, activated ABA-inducible promoters, and led to stomatal closure. Interestingly, PB and GEX1A elicited similar cellular changes, including alterations in the patterns of transcription and splicing, suggesting that these compounds might target the same spliceosome complex in plant cells. This work establishes PB and GEX1A as potent splicing inhibitors in plants that can be used to probe the assembly, dynamics, and molecular functions of the spliceosome and to study the interplay between splicing stress and abiotic stresses, as well as having potential biotechnological applications.

Estimation of the effects of multipoint pacing on battery longevity in routine clinical practice.

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Akerström, Finn; Narváez, Irene; Puchol, Alberto; Pachón, Marta; Martín-Sierra, Cristina; Rodríguez-Mañero, Moisés; Rodríguez-Padial, Luis; Arias, Miguel A

2017-09-23

Multipoint pacing (MPP) permits simultaneous multisite pacing of the left ventricle (LV); initial studies suggest haemodynamic and clinical benefits over conventional (single LV site) cardiac resynchronization therapy (CRT). The aim of this study was to estimate the impact of MPP activation on battery longevity in routine clinical practice. Patient (n = 46) and device data were collected from two centres at least 3 months after MPP-CRT device implantation. Multipoint pacing programming was based on the maximal possible anatomical LV1/LV2 separation according to three predefined LV pacing capture threshold (PCT) cut-offs (≤1.5 V; ≤4.0 V; and ≤6.5 V). Estimated battery longevity was calculated using the programmed lower rate limit, lead impedances, outputs, and pacing percentages. Relative to the longevity for conventional CRT using the lowest PCT (8.9 ± 1.2 years), MPP activation significantly shortened battery longevity for all three PCT cut-offs (≤1.5 V, -5.6%; ≤4.0 V, -16.9%; ≤6.5 V, -21.3%; P's battery longevity was significantly shortened for the MPP ≤ 4.0 V and ≤6.5 V cut-offs (-10.8 and -15.7%, respectively; P's battery longevity compared with that for conventional CRT configuration. When reasonable MPP LV vector PCTs (≤4.0 V) are achieved, the decrease in battery longevity is relatively small which may prompt the clinician to activate MPP. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Transgenerational programming of longevity and reproduction by post-eclosion dietary manipulation in Drosophila

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Xia, Brian; de Belle, Steven

2016-01-01

Accumulating evidence suggests that early-life diet may program one's health status by causing permanent alternations in specific organs, tissues, or metabolic or homeostatic pathways, and such programming effects may propagate across generations through heritable epigenetic modifications. However, it remains uninvestigated whether postnatal dietary changes may program longevity across generations. To address this question of important biological and public health implications, newly-born flies (F0) were collected and subjected to various post-eclosion dietary manipulations (PDMs) with different protein-carbohydrate (i.e., LP, IP or HP for low-, intermediate- or high-protein) contents or a control diet (CD). Longevity and fecundity analyses were performed with these treated F0 flies and their F1, F2 and F3 offspring, while maintained on CD at all times. The LP and HP PDMs shortened longevity, while the IP PDM extended longevity significantly up to the F3 generation. Furthermore, the LP reduced while the IP PDM increased lifetime fecundity across the F0-F2 generations. Our observations establish the first animal model for studying transgenerational inheritance of nutritional programming of longevity, making it possible to investigate the underlying epigenetic mechanisms and identify gene targets for drug discovery in future studies. PMID:27025190

Diacylglycerol kinase regulation of protein kinase D during oxidative stress-induced intestinal cell injury

International Nuclear Information System (INIS)

Song Jun; Li Jing; Mourot, Joshua M.; Mark Evers, B.; Chung, Dai H.

2008-01-01

We recently demonstrated that protein kinase D (PKD) exerts a protective function during oxidative stress-induced intestinal epithelial cell injury; however, the exact role of DAG kinase (DGK)ζ, an isoform expressed in intestine, during this process is unknown. We sought to determine the role of DGK during oxidative stress-induced intestinal cell injury and whether DGK acts as an upstream regulator of PKD. Inhibition of DGK with R59022 compound or DGKζ siRNA transfection decreased H 2 O 2 -induced RIE-1 cell apoptosis as measured by DNA fragmentation and increased PKD phosphorylation. Overexpression of kinase-dead DGKζ also significantly increased PKD phosphorylation. Additionally, endogenous nuclear DGKζ rapidly translocated to the cytoplasm following H 2 O 2 treatment. Our findings demonstrate that DGK is involved in the regulation of oxidative stress-induced intestinal cell injury. PKD activation is induced by DGKζ, suggesting DGK is an upstream regulator of oxidative stress-induced activation of the PKD signaling pathway in intestinal epithelial cells

C. elegans SIRT6/7 homolog SIR-2.4 promotes DAF-16 relocalization and function during stress.

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Chiang, Wei-Chung; Tishkoff, Daniel X; Yang, Bo; Wilson-Grady, Joshua; Yu, Xiaokun; Mazer, Travis; Eckersdorff, Mark; Gygi, Steven P; Lombard, David B; Hsu, Ao-Lin

2012-09-01

FoxO transcription factors and sirtuin family deacetylases regulate diverse biological processes, including stress responses and longevity. Here we show that the Caenorhabditis elegans sirtuin SIR-2.4--homolog of mammalian SIRT6 and SIRT7 proteins--promotes DAF-16-dependent transcription and stress-induced DAF-16 nuclear localization. SIR-2.4 is required for resistance to multiple stressors: heat shock, oxidative insult, and proteotoxicity. By contrast, SIR-2.4 is largely dispensable for DAF-16 nuclear localization and function in response to reduced insulin/IGF-1-like signaling. Although acetylation is known to regulate localization and activity of mammalian FoxO proteins, this modification has not been previously described on DAF-16. We find that DAF-16 is hyperacetylated in sir-2.4 mutants. Conversely, DAF-16 is acetylated by the acetyltransferase CBP-1, and DAF-16 is hypoacetylated and constitutively nuclear in response to cbp-1 inhibition. Surprisingly, a SIR-2.4 catalytic mutant efficiently rescues the DAF-16 localization defect in sir-2.4 null animals. Acetylation of DAF-16 by CBP-1 in vitro is inhibited by either wild-type or mutant SIR-2.4, suggesting that SIR-2.4 regulates DAF-16 acetylation indirectly, by preventing CBP-1-mediated acetylation under stress conditions. Taken together, our results identify SIR-2.4 as a critical regulator of DAF-16 specifically in the context of stress responses. Furthermore, they reveal a novel role for acetylation, modulated by the antagonistic activities of CBP-1 and SIR-2.4, in modulating DAF-16 localization and function.

Longevity and aging in vertebrate evolution

Energy Technology Data Exchange (ETDEWEB)

Sacher, G.A

1978-08-01

Mammalian lifespan has a close allometric association with brain weight, body weight, metabolic rate, and body temperature. Longevity, then, if governed by natural selection acting on positive genetic mechanisms for stabilizing life processes, rather than by the random accumulation of ''senescence genes.'' This paper compares the social implications of these hypotheses.

Longevity of Emplacement Drift Ground Support Materials

International Nuclear Information System (INIS)

D.H.Tang

2001-01-01

The purpose of this analysis is to evaluate the factors affecting the longevity of emplacement drift ground support materials and to develop a basis for the selection of materials for ground support that will function throughout the preclosure period of a potential repository at Yucca Mountain. REV 01 ICN 01 of this analysis is developed in accordance with AP-3.10Q, Analyses and Models, Revision 2, ICN 4, and prepared in accordance with the Technical Work Plan for Subsurface Design Section FY 01 Work Activities (CRWMS M and O 2001a). The objective of this analysis is to update the previous analysis (CRWMS M and O 2000a) to account for related changes in the Ground Control System Description Document (CRWMS M and O 2000b), the Monitored Geologic Repository Project Description Document, which is included in the Requirements and Criteria for Implementing a Repository Design that can be Operated Over a Range of Thermal Modes (BSC 2001), input information, and in environmental conditions, and to provide updated information on candidate ground support materials. Candidate materials for ground support are carbon steel and cement grout. Steel is mainly used for steel sets, lagging, channel, rock bolts, and wire mesh. Cement grout is only considered in the case of grouted rock bolts. Candidate materials for the emplacement drift invert are carbon steel and granular natural material. Materials are evaluated for the repository emplacement drift environment based on the updated thermal loading condition and waste package design. The analysis consists of the following tasks: (1) Identify factors affecting the longevity of ground support materials for use in emplacement drifts. (2) Review existing documents concerning the behavior of candidate ground support materials during the preclosure period. (3) Evaluate impacts of temperature and radiation effects on mechanical and thermal properties of steel. Assess corrosion potential of steel at emplacement drift environment. (4

Dietary regulation of hypodermal polyploidization in C. elegans.

Science.gov (United States)

Tain, Luke S; Lozano, Encarnación; Sáez, Alberto G; Leroi, Armand M

2008-03-12

Dietary restriction (DR) results in increased longevity, reduced fecundity and reduced growth in many organisms. Though many studies have examined the effects of DR on longevity and fecundity, few have investigated the effects on growth. Here we use Caenorhabditis elegans to determine the mechanisms that regulate growth under DR. We show that rather than a reduction in cell number, decreased growth in wild type C. elegans under DR is correlated with lower levels of hypodermal polyploidization. We also show that mutants lacking wild type sensory ciliated neurons are small, exhibit hypo-polyploidization and more importantly, when grown under DR, reduce their levels of endoreduplication to a lesser extent than wild type, suggesting that these neurons are required for the regulation of hypodermal polyploidization in response to DR. Similarly, we also show that the cGMP-dependent protein kinase EGL-4 and the SMA/MAB signalling pathway regulate polyploidization under DR. We show C. elegans is capable of actively responding to food levels to regulate adult ploidy. We suggest this response is dependent on the SMA/MAB signalling pathway.

Power for genetic association study of human longevity using the case-control design

DEFF Research Database (Denmark)

Tan, Qihua; Zhao, Jing Hua; Zhang, Dongfeng

2008-01-01

The efficiency of the popular case-control design in gene-longevity association studies needs to be verified because, different from a binary trait, longevity represents only the extreme end of the continuous life span distribution without a clear cutoff for defining the phenotype. In this paper...

Understanding the Posttranscriptional Regulation of Plant Responses to Abiotic Stress

KAUST Repository

Alshareef, Sahar

2017-01-01

Constitutive and alternative splicing of pre-mRNAs from multiexonic genes controls the diversity of the proteome; these precisely regulated processes also fine-tune responses to cues related to growth, development, and biotic and abiotic stresses

Extreme Longevity in Proteinaceous Deep-Sea Corals

Energy Technology Data Exchange (ETDEWEB)

Roark, E B; Guilderson, T P; Dunbar, R B; Fallon, S J; Mucciarone, D A

2009-02-09

Deep-sea corals are found on hard substrates on seamounts and continental margins world-wide at depths of 300 to {approx}3000 meters. Deep-sea coral communities are hotspots of deep ocean biomass and biodiversity, providing critical habitat for fish and invertebrates. Newly applied radiocarbon age date from the deep water proteinaceous corals Gerardia sp. and Leiopathes glaberrima show that radial growth rates are as low as 4 to 35 {micro}m yr{sup -1} and that individual colony longevities are on the order of thousands of years. The management and conservation of deep sea coral communities is challenged by their commercial harvest for the jewelry trade and damage caused by deep water fishing practices. In light of their unusual longevity, a better understanding of deep sea coral ecology and their interrelationships with associated benthic communities is needed to inform coherent international conservation strategies for these important deep-sea ecosystems.

Salivary cytokine response in the aftermath of stress: An emotion regulation perspective.

Science.gov (United States)

Newton, Tamara L; Fernandez-Botran, Rafael; Lyle, Keith B; Szabo, Yvette Z; Miller, James J; Warnecke, Ashlee J

2017-09-01

Elevated inflammation in the context of stress has been implicated in mental and physical health. Approaching this from an emotion regulation perspective, we tested whether the salivary cytokine response to stress is dampened by using distraction to minimize opportunity for poststressor rumination. Healthy young adults were randomized to an acute stressor: modified Trier Social Stress Test (TSST, Study 1) or angry memory retrieval (Study 2). Within each study, participants were randomized to poststressor condition-rest or distraction-at a 3:1 ratio. Saliva, collected before and 40 min after the end of each stressor, was assayed for proinflammatory cytokines (PICs): interleukin-1β (IL-1β), TNF-α, and IL-6. Both stressors increased all PICs, and both provoked negative emotion. At 40 min post-TSST, salivary PIC increases did not differ between distraction and rest, but correlated positively with emotional reactivity to stress. At 40 min after memory retrieval, IL-1β increases and intrusive rumination were lower during distraction than rest, but did not correlate with emotional reactivity. Trait rumination and interference control mechanisms, also measured, played little role in PIC increases. Overall, after some stressors, some salivary cytokine responses are lower during distraction than rest. The roles of specific emotions, emotional intensity, and poststressor timing of saliva collection in this finding require clarification. Furthermore, the possibility of two affective paths to inflammation in the context of stress-one sensitive to opportunities for early occurring emotion regulation (as reflected in emotional reactivity), and one sensitive to late-occurring emotion regulation (as reflected in distraction after stress)-deserves attention. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts.

Science.gov (United States)

Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Kwiatkowska, Aleksandra; Potocki, Leszek; Rawska, Ewa; Pabian, Sylwia; Kaplan, Jakub; Lewinska, Anna; Wnuk, Maciej

2016-05-24

Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages. The gains of chromosomes I, III and VI and significant changes in the gene copy number in nine functional gene categories involved in metabolic processes and stress responses were observed. Ethanol-mediated gains of YRF1 and CUP1 genes were the most accented. Ethanol also induced nucleolus fragmentation that confirms that nucleolus is a stress sensor in yeasts. Taken together, we postulate that wine yeasts of different origin may adapt to mild alcohol stress by shifts in intracellular redox state promoting growth capacity, upregulation of key regulators of longevity, namely sirtuins and changes in the dosage of genes involved in the telomere maintenance and ion detoxification.

Social exclusion, personal control, self-regulation, and stress among substance abuse treatment clients.

Science.gov (United States)

Cole, Jennifer; Logan, T K; Walker, Robert

2011-01-01

The purpose of this study was to examine the relationship of social exclusion, personal control, and self-regulation to perceived stress among individuals who participated in publicly funded substance abuse treatment. Participants entered treatment between June 2006 and July 2007 and completed a 12-month follow-up survey by telephone (n=787). The results of the OLS regression analysis indicate that individuals with greater social exclusion factors (e.g. greater economic hardship, lower subjective social standing, greater perceived discrimination), lower perceived control of one's life, and lower self-regulation had higher perceived stress. Furthermore, a significant interaction was found suggesting a stress-buffering effect of personal control between subjective social standing and perceived stress. Interestingly, income status was not significantly related to perceived stress, while economic hardship, which assesses participants' inability to meet basic expenses, was significantly associated with perceived stress. Future research should examine how to integrate the AA/NA teaching about powerlessness and its role in recovery with the importance of increased personal control and self-control in decreasing perceived stress. Implications for future research and substance abuse treatment are discussed. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

A Study of the Longevity of Hebrew Slang

Science.gov (United States)

Kornblueth, Ilana; Aynor, Sarah

1974-01-01

Investigates the following as possibly related to the longevity of slang items in Hebrew: the language of origin, the category of content, structural characteristics and the background characteristics of the users. (PM)

Regulation of the corticosteroid signalling system in rainbow trout HPI axis during confinement stress.

Science.gov (United States)

Kiilerich, Pia; Servili, Arianna; Péron, Sandrine; Valotaire, Claudiane; Goardon, Lionel; Leguen, Isabelle; Prunet, Patrick

2018-03-01

This study aims to shed light on corticosteroid regulation of stress in teleost fish with focus on the corticosteroid signalling system. The role of the mineralocorticoid-like hormone 11-deoxycorticosterone (DOC) in fish is still enigmatic, as is the function of the mineralocorticoid receptor, MR. Low plasma DOC levels and ubiquitous tissue distribution of MR question the physiological relevance of the mineralocorticoid-axis. Furthermore, the particular purpose of each of the three corticosteroid receptors in fish, the glucocorticoid receptors, GR1 and GR2, and the MR, is still largely unknown. Therefore we investigate the regulation of cortisol and DOC in plasma and mRNA levels of MR, GR1 and GR2 in the HPI-axis tissues (hypothalamus, pituitary and interrenal gland) during a detailed confinement stress time-course. Here we show a sustained up-regulation of plasma DOC levels during a confinement stress time-course. However, the low DOC levels compared to cortisol measured in the plasma do not favour an activity of DOC through MR receptors. Furthermore, we show differential contribution of the CRs in regulation and control of HPI axis activity following confinement stress. Judged by the variation of mRNA levels negative feedback regulation of cortisol release occurs on the level of the pituitary via MR and on the level of the interrenal gland via GR2. Finally, asa significant effect of confinement stress on CR expressions was observed in the pituitary gland, we completed this experiment by demonstrating that corticosteroid receptors (GR1, GR2 and MR) are co-expressed in the ACTH cells located in the adenohypophysis. Overall, these data suggest the involvement of these receptors in the regulation of the HPI axis activity by cortisol. Copyright © 2017 Elsevier Inc. All rights reserved.

Can early-life growth disruptions predict longevity? Testing the association between vertebral neural canal (VNC) size and age-at-death.

Science.gov (United States)

Amoroso, Alexandra; Garcia, Susana J

2018-04-04

This study tests the association of vertebral neural canal (VNC) size and age-at-death in a Portuguese skeletal collection from the 19 th -20th century. If the plasticity and constraint model best explains this association, VNC size would be negatively related to mortality risk. If the predictive adaptive response (PAR) model is a better fit, no association can be inferred between VNC size and age-at-death. Ninety individuals were used in this study. The anteroposterior and transverse diameters of all vertebrae were measured. A Cox regression analysis was performed by sex to assess the effect of VNC size on age-at-death, after adjusting for the effects of year of birth and cause of death. Several measurements of VNC diameters have a statistically significant effect on age-at-death, but when the covariates were considered, this association became non-significant. The PAR model seems the best fit to explain the relation between VNC and age-at-death. Individuals who went through stressful events early in life were prepared to face a stressful environment later in life, allowing them to cope with adversity without affecting longevity. However, developmental plasticity may be buffered by maternal capital accumulated over several generations, and health hazards encountered throughout life can contribute to health outcomes and longevity. Copyright © 2018 Elsevier Inc. All rights reserved.

Perfectionism related to self-reported insomnia severity, but not when controlled for stress and emotion regulation.

Science.gov (United States)

Brand, Serge; Kirov, Roumen; Kalak, Nadeem; Gerber, Markus; Pühse, Uwe; Lemola, Sakari; Correll, Christoph U; Cortese, Samuele; Meyer, Till; Holsboer-Trachsler, Edith

2015-01-01

Perfectionism is understood as a set of personality traits such as unrealistically high and rigid standards for performance, fear of failure, and excessive self-criticism. Previous studies showed a direct association between increased perfectionism and poor sleep, though without taking into account possible mediating factors. Here, we tested the hypothesis that perfectionism was directly associated with poor sleep, and that this association collapsed, if mediating factors such as stress and poor emotion regulation were taken into account. Three hundred and forty six young adult students (M=23.87 years) completed questionnaires relating to perfectionism traits, sleep, and psychological functioning such as stress perception, coping with stress, emotion regulation, and mental toughness. Perfectionism was directly associated with poor sleep and poor psychological functioning. When stress, poor coping, and poor emotion regulation were entered in the equation, perfectionism traits no longer contributed substantively to the explanation of poor sleep. Though perfectionism traits seem associated with poor sleep, the direct role of such traits seemed small, when mediating factors such as stress perception and emotion regulation were taken into account.

AB126. Association between FOX03A gene polymorphisms and human longevity: a meta-analysis

OpenAIRE

Zhao, Shanchao; Bao, Jiming; Song, Xianlu

2016-01-01

Objective Numerous studies have shown associations between the FOX03A gene, encoding the forkhead box 03 transcription factor, and human or specifically male longevity. However, the associations of specific FOX03A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. Methods A comprehensive search was conducted to identify studies of FOX03A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% c...

Beyond allostatic load: rethinking the role of stress in regulating human development.

Science.gov (United States)

Ellis, Bruce J; Del Giudice, Marco

2014-02-01

How do exposures to stress affect biobehavioral development and, through it, psychiatric and biomedical disorder? In the health sciences, the allostatic load model provides a widely accepted answer to this question: stress responses, while essential for survival, have negative long-term effects that promote illness. Thus, the benefits of mounting repeated biological responses to threat are traded off against costs to mental and physical health. The adaptive calibration model, an evolutionary-developmental theory of stress-health relations, extends this logic by conceptualizing these trade-offs as decision nodes in allocation of resources. Each decision node influences the next in a chain of resource allocations that become instantiated in the regulatory parameters of stress response systems. Over development, these parameters filter and embed information about key dimensions of environmental stress and support, mediating the organism's openness to environmental inputs, and function to regulate life history strategies to match those dimensions. Drawing on the adaptive calibration model, we propose that consideration of biological fitness trade-offs, as delineated by life history theory, is needed to more fully explain the complex relations between developmental exposures to stress, stress responsivity, behavioral strategies, and health. We conclude that the adaptive calibration model and allostatic load model are only partially complementary and, in some cases, support different approaches to intervention. In the long run, the field may be better served by a model informed by life history theory that addresses the adaptive role of stress response systems in regulating alternative developmental pathways.

Low-Temperature Stress during Capped Brood Stage Increases Pupal Mortality, Misorientation and Adult Mortality in Honey Bees

Science.gov (United States)

Wang, Qing; Xu, Xinjian; Zhu, Xiangjie; Chen, Lin; Zhou, Shujing; Huang, Zachary Y.; Zhou, Bingfeng

2016-01-01

Honey bees (Apis mellifera) are key pollinators, playing a vital role in ecosystem maintenance and stability of crop yields. Recently, reduced honey bee survival has attracted intensive attention. Among all other honey bee stresses, temperature is a fundamental ecological factor that has been shown to affect honey bee survival. Yet, the impact of low temperature stress during capped brood on brood mortality has not been systematically investigated. In addition, little was known about how low temperature exposure during capped brood affects subsequent adult longevity. In this study, capped worker broods at 12 different developmental stages were exposed to 20°C for 12, 24, 36, 48, 60, 72, 84 and 96 hours, followed by incubation at 35°C until emergence. We found that longer durations of low temperature during capped brood led to higher mortality, higher incidences of misorientation inside cells and shorter worker longevity. Capped brood as prepupae and near emergence were more sensitive to low-temperature exposure, while capped larvae and mid-pupal stages showed the highest resistance to low-temperature stress. Our results suggest that prepupae and pupae prior to eclosion are the most sensitive stages to low temperature stress, as they are to other stresses, presumably due to many physiological changes related to metamorphosis happening during these two stages. Understanding how low-temperature stress affects honey bee physiology and longevity can improve honey bee management strategies. PMID:27149383

Stress responsiveness of the hypothalamic-pituitary-adrenal axis: age-related features of the vasopressinergic regulation

Directory of Open Access Journals (Sweden)

Nadezhda Dmitrievna Goncharova

2013-03-01

Full Text Available The hypothalamic-pituitary-adrenal (HPA axis plays a key role in adaptation to environmental stresses. Parvicellular neurons of the hypothalamic paraventricular nucleus secrete corticotrophin releasing hormone (CRH and arginine vasopressin (AVP into pituitary portal system; CRH and AVP stimulate ACTH release through specific G protein-coupled membrane receptors on pituitary corticotrophs, CRH1 for CRH and V1b for AVP; the adrenal gland cortex secretes glucocorticoids in response ACTH. The glucocorticoids activate specific receptors in brain and peripheral tissues thereby triggering the necessary metabolic, immune, neuromodulatory and behavioral changes to resist stress. While importance of CRH, as a key hypothalamic factor of HPA axis regulation in basal and stress conditions in most species, is generally recognized, role of AVP remains to be clarified. This review focuses on the role of AVP in the regulation of stress responsiveness of the HPA axis with emphasis on the effects of aging on vasopressinergic regulation of HPA axis stress responsiveness. Under most of the known stressors, AVP is necessary for acute ACTH secretion but in a context-specific manner. The current data on the AVP role in regulation of HPA responsiveness to chronic stress in adulthood are rather contradictory. The importance of the vasopressinergic regulation of the HPA stress responsiveness is greatest during fetal development, in neonatal period, and in the lactating adult. Aging associated with increased variability in several parameters of HPA function including basal state, responsiveness to stressors, and special testing. Reports on the possible role of the AVP/V1b receptor system in the increase of HPA axis hyperactivity with aging are contradictory and requires further research. Many contradictory results may be due to age and species differences in the HPA function of rodents and primates.

Intellectual maturity and longevity : Late-blooming composers and writers live longer than child prodigies

NARCIS (Netherlands)

Hafkamp, Maurits P. J.; Slaets, Joris P. J.; van Bodegom, David

Life history theory links human physical and sexual development to longevity. However, there have been no studies on the association of intellectual development with longevity. This observational study investigates the relationship between the onset of intellectual maturity and lifespan through the

Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

Directory of Open Access Journals (Sweden)

Michael A Petrie

Full Text Available Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat and mechanical stress (vibration on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction.The purpose of this study is to examine whether active mechanical stress (muscle contraction, passive mechanical stress (vibration, or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair.Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus to analyze mRNA gene expression.We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold, PGC-1α (5.46 fold, and ABRA (5.98 fold; and repressed MSTN (0.56 fold. Heat stress repressed PGC-1α (0.74 fold change; p < 0.05; while vibration induced FOXK2 (2.36 fold change; p < 0.05. Vibration similarly caused a down regulation of MSTN (0.74 fold change; p < 0.05, but to a lesser extent than active muscle contraction. Vibration induced FOXK2 (p < 0.05 while heat stress repressed PGC-1α (0.74 fold and ANKRD1 genes (0.51 fold; p < 0.05.These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell

Health Status and Health Dynamics in an Empirical Model of Expected Longevity*

Science.gov (United States)

Benítez-Silva, Hugo; Ni, Huan

2010-01-01

Expected longevity is an important factor influencing older individuals’ decisions such as consumption, savings, purchase of life insurance and annuities, claiming of Social Security benefits, and labor supply. It has also been shown to be a good predictor of actual longevity, which in turn is highly correlated with health status. A relatively new literature on health investments under uncertainty, which builds upon the seminal work by Grossman (1972), has directly linked longevity with characteristics, behaviors, and decisions by utility maximizing agents. Our empirical model can be understood within that theoretical framework as estimating a production function of longevity. Using longitudinal data from the Health and Retirement Study, we directly incorporate health dynamics in explaining the variation in expected longevities, and compare two alternative measures of health dynamics: the self-reported health change, and the computed health change based on self-reports of health status. In 38% of the reports in our sample, computed health changes are inconsistent with the direct report on health changes over time. And another 15% of the sample can suffer from information losses if computed changes are used to assess changes in actual health. These potentially serious problems raise doubts regarding the use and interpretation of the computed health changes and even the lagged measures of self-reported health as controls for health dynamics in a variety of empirical settings. Our empirical results, controlling for both subjective and objective measures of health status and unobserved heterogeneity in reporting, suggest that self-reported health changes are a preferred measure of health dynamics. PMID:18187217

Differential regulation of mitochondrial pyruvate carrier genes modulates respiratory capacity and stress tolerance in yeast.

Directory of Open Access Journals (Sweden)

Alba Timón-Gómez

Full Text Available Mpc proteins are highly conserved from yeast to humans and are necessary for the uptake of pyruvate at the inner mitochondrial membrane, which is used for leucine and valine biosynthesis and as a fuel for respiration. Our analysis of the yeast MPC gene family suggests that amino acid biosynthesis, respiration rate and oxidative stress tolerance are regulated by changes in the Mpc protein composition of the mitochondria. Mpc2 and Mpc3 are highly similar but functionally different: Mpc2 is most abundant under fermentative non stress conditions and important for amino acid biosynthesis, while Mpc3 is the most abundant family member upon salt stress or when high respiration rates are required. Accordingly, expression of the MPC3 gene is highly activated upon NaCl stress or during the transition from fermentation to respiration, both types of regulation depend on the Hog1 MAP kinase. Overexpression experiments show that gain of Mpc2 function leads to a severe respiration defect and ROS accumulation, while Mpc3 stimulates respiration and enhances tolerance to oxidative stress. Our results identify the regulated mitochondrial pyruvate uptake as an important determinant of respiration rate and stress resistance.

Differential regulation of mitochondrial pyruvate carrier genes modulates respiratory capacity and stress tolerance in yeast.

Science.gov (United States)

Timón-Gómez, Alba; Proft, Markus; Pascual-Ahuir, Amparo

2013-01-01

Mpc proteins are highly conserved from yeast to humans and are necessary for the uptake of pyruvate at the inner mitochondrial membrane, which is used for leucine and valine biosynthesis and as a fuel for respiration. Our analysis of the yeast MPC gene family suggests that amino acid biosynthesis, respiration rate and oxidative stress tolerance are regulated by changes in the Mpc protein composition of the mitochondria. Mpc2 and Mpc3 are highly similar but functionally different: Mpc2 is most abundant under fermentative non stress conditions and important for amino acid biosynthesis, while Mpc3 is the most abundant family member upon salt stress or when high respiration rates are required. Accordingly, expression of the MPC3 gene is highly activated upon NaCl stress or during the transition from fermentation to respiration, both types of regulation depend on the Hog1 MAP kinase. Overexpression experiments show that gain of Mpc2 function leads to a severe respiration defect and ROS accumulation, while Mpc3 stimulates respiration and enhances tolerance to oxidative stress. Our results identify the regulated mitochondrial pyruvate uptake as an important determinant of respiration rate and stress resistance.

Impacts of Dietary Phytochemicals in the Presence and Absence of Pesticides on Longevity of Honey Bees (Apis mellifera

Directory of Open Access Journals (Sweden)

Ling-Hsiu Liao

2017-02-01

Full Text Available Because certain flavonols and phenolic acids are found in pollen and nectar of most angiosperms, they are routinely ingested by Apis mellifera, the western honey bee. The flavonol quercetin and the phenolic acid p-coumaric acid are known to upregulate detoxification enzymes in adult bees; their presence or absence in the diet may thus affect the toxicity of ingested pesticides. We conducted a series of longevity assays with one-day-old adult workers to test if dietary phytochemicals enhance longevity and pesticide tolerance. One-day-old bees were maintained on sugar syrup with or without casein (a phytochemical-free protein source in the presence or absence of quercetin and p-coumaric acid as well as in the presence or absence of two pyrethroid insecticides, bifenthrin and β-cyfluthrin. Dietary quercetin (hazard ratio, HR = 0.82, p-coumaric acid (HR = 0.91 and casein (HR = 0.74 were associated with extended lifespan and the two pyrethroid insecticides, 4 ppm bifenthrin (HR = 9.17 and 0.5 ppm β-cyfluthrin (HR = 1.34, reduced lifespan. Dietary quercetin enhanced tolerance of both pyrethroids; p-coumaric acid had a similar effect trend, although of reduced magnitude. Casein in the diet appears to eliminate the life-prolonging effect of p-coumaric acid in the absence of quercetin. Collectively, these assays demonstrate that dietary phytochemicals influence honey bee longevity and pesticide stress; substituting sugar syrups for honey or yeast/soy flour patties may thus have hitherto unrecognized impacts on adult bee health.

Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage

Science.gov (United States)

Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked: considerable variation in oxidative stress resistance exists among and within species and ...

Central roles of iron in the regulation of oxidative stress in the yeast Saccharomyces cerevisiae.

Science.gov (United States)

Matsuo, Ryo; Mizobuchi, Shogo; Nakashima, Maya; Miki, Kensuke; Ayusawa, Dai; Fujii, Michihiko

2017-10-01

Oxygen is essential for aerobic organisms but causes cytotoxicity probably through the generation of reactive oxygen species (ROS). In this study, we screened for the genes that regulate oxidative stress in the yeast Saccharomyces cerevisiae, and found that expression of CTH2/TIS11 caused an increased resistance to ROS. CTH2 is up-regulated upon iron starvation and functions to remodel metabolism to adapt to iron starvation. We showed here that increased resistance to ROS by CTH2 would likely be caused by the decreased ROS production due to the decreased activity of mitochondrial respiration, which observation is consistent with the fact that CTH2 down-regulates the mitochondrial respiratory proteins. We also found that expression of CTH1, a paralog of CTH2, also caused an increased resistance to ROS. This finding supported the above view, because mitochondrial respiratory proteins are the common targets of CTH1 and CTH2. We further showed that supplementation of iron in medium augmented the growth of S. cerevisiae under oxidative stress, and expression of CTH2 and supplementation of iron collectively enhanced its growth under oxidative stress. Since CTH2 is regulated by iron, these findings suggested that iron played crucial roles in the regulation of oxidative stress in S. cerevisiae.

The impact of biomedical innovation on longevity and health

Directory of Open Access Journals (Sweden)

Frank R Lichtenberg

2015-03-01

Full Text Available Many authors have expressed the view that a substantial portion of recent gains in longevity and health is due to biomedical research and innovation. This article describes the methodologies and findings of a number of studies based on observational data that have sought to measure the impact of biomedical innovation on the longevity and health of Americans and other populations during recent decades. Most of these studies have examined the impact of innovation in pharmaceuticals, the most research-intensive medical good or service. Two measures of medical innovation that have been used are the mean vintage of the medical goods or procedures used by an individual or population, and the number of distinct products (e.g. drugs available for treating a condition. Longevity (e.g. time till death is the health outcome that has been analyzed the most, but several studies have studied the impact of medical (i.e. pharmaceutical innovation on the ability of people to work or engage in activities of daily living. Some studies have been based on cross-sectional patient-level data. Others have been based on longitudinal, region-level data; they have investigated whether regions (e.g. states undergoing more rapid medical innovation have exhibited larger improvements in health. And some studies have been based on longitudinal, disease-level data; they have investigated whether the medical conditions undergoing more rapid innovation have exhibited larger gains in health outcomes. Innovation related to some specific major diseases (e.g. cardiovascular disease and cancer has been investigated, but the overall impact of innovation related to other major diseases (e.g. diabetes has not.These studies provide considerable support for the hypothesis that a substantial portion of recent gains in longevity and health is due to biomedical research and innovation. It would be desirable to apply these methods to data from developing countries.

Clinical Outcomes Measures for Assessment of Longevity in the Dental Implant Literature : ORONet Approach

NARCIS (Netherlands)

Bassi, Francesco; Carr, Alan B.; Chang, Ting-Ling; Estafanous, Emad; Garrett, Neal R.; Happonen, Risto-Pekka; Koka, Sreenivas; Laine, Juhani; Osswald, Martin; Reintsema, Harry; Rieger, Jana; Roumanas, Eleni; Salinas, Thomas J.; Stanford, Clark M.; Wolfaardt, Johan

2013-01-01

The Oral Rehabilitation Outcomes Network (ORONet) Longevity Working Group undertook a search of the literature from 1995 to 2009 on randomized controlled trials related to longevity of osseointegrated implants. Outcomes measures used in these studies were identified and subjected to the OMERACT

DNA demethylases target promoter transposable elements to positively regulate stress responsive genes in Arabidopsis.

Science.gov (United States)

Le, Tuan-Ngoc; Schumann, Ulrike; Smith, Neil A; Tiwari, Sameer; Au, Phil Chi Khang; Zhu, Qian-Hao; Taylor, Jennifer M; Kazan, Kemal; Llewellyn, Danny J; Zhang, Ren; Dennis, Elizabeth S; Wang, Ming-Bo

2014-09-17

DNA demethylases regulate DNA methylation levels in eukaryotes. Arabidopsis encodes four DNA demethylases, DEMETER (DME), REPRESSOR OF SILENCING 1 (ROS1), DEMETER-LIKE 2 (DML2), and DML3. While DME is involved in maternal specific gene expression during seed development, the biological function of the remaining DNA demethylases remains unclear. We show that ROS1, DML2, and DML3 play a role in fungal disease resistance in Arabidopsis. A triple DNA demethylase mutant, rdd (ros1 dml2 dml3), shows increased susceptibility to the fungal pathogen Fusarium oxysporum. We identify 348 genes differentially expressed in rdd relative to wild type, and a significant proportion of these genes are downregulated in rdd and have functions in stress response, suggesting that DNA demethylases maintain or positively regulate the expression of stress response genes required for F. oxysporum resistance. The rdd-downregulated stress response genes are enriched for short transposable element sequences in their promoters. Many of these transposable elements and their surrounding sequences show localized DNA methylation changes in rdd, and a general reduction in CHH methylation, suggesting that RNA-directed DNA methylation (RdDM), responsible for CHH methylation, may participate in DNA demethylase-mediated regulation of stress response genes. Many of the rdd-downregulated stress response genes are downregulated in the RdDM mutants nrpd1 and nrpe1, and the RdDM mutants nrpe1 and ago4 show enhanced susceptibility to F. oxysporum infection. Our results suggest that a primary function of DNA demethylases in plants is to regulate the expression of stress response genes by targeting promoter transposable element sequences.

Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism

DEFF Research Database (Denmark)

Jansen, S W; Akintola, A A; Roelfsema, F

2015-01-01

hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring...... of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis...... may favour longevity without altering energy metabolism....

Efikasi Chitosan untuk Memperpanjang Flower Longevity Bunga Anggrek Dendrobium Hibrida dalam Pot (Potted Flower

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I MADE SUKEWIJAYA

2015-09-01

Full Text Available Effication of Chitosan on Lengthening The Flower Longevity of Potted Orchid ofDendrobium Hybrid. The aim of the current research is to investigate general effects of Chitosantreatment on the flowering of Dendrobium orchid and to find out the optimum concentration of Chitosanin lengthening flower longevity of potted orchid of Dendrobium hybrid. Results of the research showedthat Chitosan application significantly affected variables of the number of flower per-plant, the length ofindividual flower, period of time to get full blooming, and the flower longevity. The best results for thoseof variables was achieved with Chitosan concentration of 0.15%.

Natural modifiers of seed longevity in the Arabidopsis mutants abscisic acid insensitive3-5 (abi3-5) and leafy cotyledon1-3 (lec1-3)

NARCIS (Netherlands)

Sugliani, M.R.L.; Rajjou, L.; Clerkx, E.J.M.; Koornneef, M.; Soppe, W.J.J.

2009-01-01

• Seed longevity is an important trait in many crops and is essential for the success of most land plant species. Current knowledge of its molecular regulation is limited. The Arabidopsis mutants abscisic acid insensitive3-5 (abi3-5) and leafy cotyledon1-3 (lec1-3) have impaired seed maturation and

[Effect of physical activity on longevity].

Science.gov (United States)

Wilczek, Mateusz M; Krupienicz, Andrzej

2016-11-25

Multiple population studies have reported a positive correlation between higher levels of physical activity (PA) and longer lifespan. It has been generally accepted that it occurs due to PA having a direct effect on longevity. However, this idea is negated by experiments on animal models and an observational study on a twin cohort published recently by Karvinen et al. This unique study includes a pairwise comparison of monozygotic twins discordant for PA, therefore eliminating any influence of genetic factors on both mortality and tendency to take up exercise. The intriguing lack of differences in lifespan in such pairs implies that PA is not an important life prolonging factor. This discovery casts doubt on the validity of PA recommendations found in numerous medical guidelines. Nevertheless, the mentioned results apply only to the plain PA - longevity relation. They do not consider health benefits of PA, for which solid evidence exists. In particular, PA clearly reduces the risk of obesity-related diseases. This may indirectly yet significantly affect the length and quality of life, even if the direct relationship between PA and lifespan will be proven false in further research. © 2016 MEDPRESS.

Mediterranean Way of Drinking and Longevity.

Science.gov (United States)

Giacosa, Attilio; Barale, Roberto; Bavaresco, Luigi; Faliva, Milena Anna; Gerbi, Vincenzo; La Vecchia, Carlo; Negri, Eva; Opizzi, Annalisa; Perna, Simone; Pezzotti, Mario; Rondanelli, Mariangela

2016-01-01

The relation between alcohol consumption and mortality is a J-shaped curve in most of the many studies published on this topic. The Copenhagen Prospective Population Studies demonstrated in the year 2000 that wine intake may have a beneficial effect on all cause mortality that is additive to that of alcohol. Wine contains various poliphenolic substances which may be beneficial for health and in particular flavonols (such as myricetin and quercetin), catechin and epicatechin, proanthocyanidins, anthocyanins, various phenolic acids and the stilbene resveratrol. In particular, resveratrol seems to play a positive effect on longevity because it increases the expression level of Sirt1, besides its antioxidant, anti-inflammatory and anticarcinogenic properties. Moderate wine drinking is part of the Mediterranean diet, together with abundant and variable plant foods, high consumption of cereals, olive oil as the main (added) fat and a low intake of (red) meat. This healthy diet pattern involves a "Mediterranean way of drinking," that is a regular, moderate wine consumption mainly with food (up to two glasses a day for men and one glass for women). Moderate wine drinking increases longevity, reduces the risk of cardiovascular diseases and does not appreciably influence the overall risk of cancer.

Human Longevity : nature vs nurture-fact or fiction.

Energy Technology Data Exchange (ETDEWEB)

Carnes, B. A.; Jay Olshansky, S.; Gavrilov, L.; Gavrilova, N.; Grahn, D.; Center for Mechanistic Biology and Biotechnology; Univ. of Chicago

1999-04-01

Genetic effects may have a greater influence on human longevity than biomedical intervention. An alternative perspective examines the heritability effects of genetic damage caused by free radicals within somatic cells, or genetic damage that accumulates over a lifetime.

Educators' emotion regulation strategies and their physiological indicators of chronic stress over 1 year.

Science.gov (United States)

Katz, Deirdre A; Harris, Alexis; Abenavoli, Rachel; Greenberg, Mark T; Jennings, Patricia A

2018-04-01

Studies show teaching is a highly stressful profession and that chronic work stress is associated with adverse health outcomes. This study analysed physiological markers of stress and self-reported emotion regulation strategies in a group of middle school teachers over 1 year. Chronic physiological stress was assessed with diurnal cortisol measures at three time points over 1 year (fall, spring, fall). The aim of this longitudinal study was to investigate the changes in educators' physiological level of stress. Results indicate that compared to those in the fall, cortisol awakening responses were blunted in the spring. Further, this effect was ameliorated by the summer break. Additionally, self-reported use of the emotion regulation strategy reappraisal buffered the observed blunting that occurred in the spring. Copyright © 2017 John Wiley & Sons, Ltd.

Recent advances in human gene-longevity association studies

DEFF Research Database (Denmark)

De Benedictis, G; Tan, Q; Jeune, B

2001-01-01

This paper reviews the recent literature on genes and longevity. The influence of genes on human life span has been confirmed in studies of life span correlation between related individuals based on family and twin data. Results from major twin studies indicate that approximately 25......% of the variation in life span is genetically determined. Taking advantage of recent developments in molecular biology, researchers are now searching for candidate genes that might have an influence on life span. The data on unrelated individuals emerging from an ever-increasing number of centenarian studies makes...... this possible. This paper summarizes the rich literature dealing with the various aspects of the influence of genes on individual survival. Common phenomena affecting the development of disease and longevity are discussed. The major methodological difficulty one is confronted with when studying the epidemiology...

The Trade-Off between Female Fertility and Longevity during the Epidemiological Transition in the Netherlands

DEFF Research Database (Denmark)

Kaptijn, Ralf; Thomese, Fleur; Liefbroer, Aart C

2015-01-01

as an evolutionary trade-off between reproduction and survival. We examine the relationship between fertility and longevity during the epidemiological transition in the Netherlands. This period of rapid decline in mortality from infectious diseases offers a good opportunity to study the relationship between...... fertility and longevity, using registry data from 6,359 women born in The Netherlands between 1850 and 1910. We hypothesize that an initially negative relationship between women's fertility and their longevity gradually turns less negative during the epidemiological transition, because of decreasing costs...

Worker life tables, survivorship, and longevity in colonies of Bombus (Fervidobombus atratus (Hymenoptera: Apidae

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Eunice Vieira da Silva-Matos

2000-06-01

Full Text Available Survivorship curves and longevity of workers were studied in two queenright and two queenless colonies of Bombus (Fervidobombus atratus. Survivorship curves for workers of all colonies were, in general, convex, indicating an increasing mortality rate with increasing age. The mean longevity for the workers from queenright colonies, 24.3 days and 17.6 days, was not significantly different from that in queenless colonies, 21.2 days and 20.2 days. In all colonies workers started foraging activities when aged 0-5 days, and the potential forager rates rose progressively with increasing age. Mortality rates within each age interval were significantly correlated with the foraging worker rates in all colonies. Only in two of the colonies (one queenright and one queenless longevity was significantly correlated with worker size. The duration of brood development period seems to be one of the most important factors influencing adult worker longevity in this bumble bee species.

Yeast aquaporin regulation by 4-hydroxynonenal is implicated in oxidative stress response.

Science.gov (United States)

Rodrigues, Claudia; Tartaro Bujak, Ivana; Mihaljević, Branka; Soveral, Graça; Cipak Gasparovic, Ana

2017-05-01

Reactive oxygen species, especially hydrogen peroxide (H 2 O 2 ), contribute to functional molecular impairment and cellular damage, but also are necessary in normal cellular metabolism, and in low doses play stimulatory role in cell proliferation and stress resistance. In parallel, reactive aldehydes such as 4-hydroxynonenal (HNE), are lipid peroxidation breakdown products which also contribute to regulation of numerous cellular processes. Recently, channeling of H 2 O 2 by some mammalian aquaporin isoforms has been reported and suggested to contribute to aquaporin involvement in cancer malignancies, although the mechanism by which these membrane water channels are implicated in oxidative stress is not clear. In this study, two yeast models with increased levels of membrane polyunsaturated fatty acids (PUFAs) and aquaporin AQY1 overexpression, respectively, were used to evaluate their interplay in cell's oxidative status. In particular, the aim of the study was to investigate if HNE accumulation could affect aquaporin function with an outcome in oxidative stress response. The data showed that induction of aquaporin expression by PUFAs results in increased water permeability in yeast membranes and that AQY1 activity is impaired by HNE. Moreover, AQY1 expression increases cellular sensitivity to oxidative stress by facilitating H 2 O 2 influx. On the other hand, AQY1 expression has no influence on the cellular antioxidant GSH levels and catalase activity. These results strongly suggest that aquaporins are important players in oxidative stress response and could contribute to regulation of cellular processes by regulation of H 2 O 2 influx. © 2017 IUBMB Life, 69(5):355-362, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Vasomotor Regulation of Coronary Microcirculation by Oxidative Stress: Role of Arginase

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Lih eKuo

2013-08-01

Full Text Available Overproduction of reactive oxygen species, i.e., oxidative stress, is associated with the activation of redox signaling pathways linking to inflammatory insults and cardiovascular diseases by impairing endothelial function and consequently blood flow dysregulation due to microvascular dysfunction. This review focuses on the regulation of vasomotor function in the coronary microcirculation by endothelial nitric oxide (NO during oxidative stress and inflammation related to the activation of L-arginine consuming enzyme arginase. Superoxide produced in the vascular wall compromises vasomotor function by not only scavenging endothelium-derived NO but also inhibiting prostacyclin synthesis due to formation of peroxynitrite. The upregulation of arginase contributes to the deficiency of endothelial NO and microvascular dysfunction in various vascular diseases by initiating or following oxidative stress and inflammation. Hydrogen peroxide, a diffusible and stable oxidizing agent, exerts vasodilator function and plays important roles in the physiological regulation of coronary blood flow. In occlusive coronary ischemia, the release of hydrogen peroxide from the microvasculature helps to restore vasomotor function of coronary collateral microvessels with exercise training. However, excessive production and prolonged exposure of microvessels to hydrogen peroxide impairs NO-mediated endothelial function by reducing L-arginine availability through hydroxyl radical-dependent upregulation of arginase. The redox signaling can be a double-edged sword in the microcirculation, which helps tissue survival in one way by improving vasomotor regulation and elicits oxidative stress and tissue injury in the other way by causing vascular dysfunction. The impact of vascular arginase on the development of vasomotor dysfunction associated with angiotensin II receptor activation, hypertension, ischemia-reperfusion, hypercholesterolemia and inflammatory insults is discussed.

The comparison of species longevity and size evolution in fossilized dinosaurs vs. fossilized mammals

Science.gov (United States)

Baeza, E.; Srinath, A.; Hernandez, A.; Heim, N.; Payne, J.

2016-12-01

For over 200 million years, two animal groups have been competing for dominance over Earth: the reptiles, (in this case, dinosaurs), and the mammals. At the beginning of the Triassic, mammals were small, rat-like creatures that were dwarfed by the dinosaurs. Dinosaurs progressively continued to grow larger throughout the Jurassic and Cretaceous periods, thus outweighing and outliving the current mammals. But at the end of the Cretaceous, the K-T mass extinction occurred, and that wiped out the dinosaurs from the face of the Earth. After the disappearance of dinosaurs, mammals started to grow larger to fill the niches that the dinosaurs left open. With this evolution in mammals, would they be able to match or even beat the dinosaur's previous records? To judge that, we need to utilize two significant factors to help judge our answer. The two factors that set them apart were body mass and longevity. Documenting the body mass shows us how much the animal weighed compared to other species. The heaviest animal in our data set weighed 77 tons. The other factor is longevity, which indicates how long a certain species has existed on a geologic time scale. The longest living animal species in our data set lived for over 20 million years. With all the data we have analyzed, we have conducted research on this subject to find out how terrestrial mammals contrasted dinosaurs in the terms of body mass and species longevity. Our research brought us to the conclusion that mammals could not overtake the body mass and longevity of dinosaurs. Although mammals came pretty close to overlapping the dinosaurs' body masses, they were just below them marginally. We had a similar pattern in longevity, where we found out that heavier animals tended to have longer longevity, therefore the dinosaurs came out on top. Additionally, we did another contrast between Mesozoic and Cenozoic mammals, where Cenozoic mammals were larger, but both had similar longevities.

Is rate of skin wound healing associated with aging or longevity phenotype?

Science.gov (United States)

Yanai, Hagai; Budovsky, Arie; Tacutu, Robi; Fraifeld, Vadim E

2011-12-01

Wound healing (WH) is a fundamental biological process. Is it associated with a longevity or aging phenotype? In an attempt to answer this question, we compared the established mouse models with genetically modified life span and also an altered rate of WH in the skin. Our analysis showed that the rate of skin WH in advanced ages (but not in the young animals) may be used as a marker for biological age, i.e., to be indicative of the longevity or aging phenotype. The ability to preserve the rate of skin WH up to an old age appears to be associated with a longevity phenotype, whereas a decline in WH-with an aging phenotype. In the young, this relationship is more complex and might even be inversed. While the aging process is likely to cause wounds to heal slowly, an altered WH rate in younger animals could indicate a different cellular proliferation and/or migration capacity, which is likely to affect other major processes such as the onset and progression of cancer. As a point for future studies on WH and longevity, using only young animals might yield confusing or misleading results, and therefore including older animals in the analysis is encouraged.

The influence of work-related chronic stress on the regulation of emotion and on functional connectivity in the brain.

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Armita Golkar

Full Text Available Despite mounting reports about the negative effects of chronic occupational stress on cognitive and emotional functions, the underlying mechanisms are unknown. Recent findings from structural MRI raise the question whether this condition could be associated with a functional uncoupling of the limbic networks and an impaired modulation of emotional stress. To address this, 40 subjects suffering from burnout symptoms attributed to chronic occupational stress and 70 controls were investigated using resting state functional MRI. The participants' ability to up- regulate, down-regulate, and maintain emotion was evaluated by recording their acoustic startle response while viewing neutral and negatively loaded images. Functional connectivity was calculated from amygdala seed regions, using explorative linear correlation analysis. Stressed subjects were less capable of down-regulating negative emotion, but had normal acoustic startle responses when asked to up-regulate or maintain emotion and when no regulation was required. The functional connectivity between the amygdala and the anterior cingulate cortex correlated with the ability to down-regulate negative emotion. This connectivity was significantly weaker in the burnout group, as was the amygdala connectivity with the dorsolateral prefrontal cortex and the motor cortex, whereas connectivity from the amygdala to the cerebellum and the insular cortex were stronger. In subjects suffering from chronic occupational stress, the functional couplings within the emotion- and stress-processing limbic networks seem to be altered, and associated with a reduced ability to down-regulate the response to emotional stress, providing a biological substrate for a further facilitation of the stress condition.

The Influence of Work-Related Chronic Stress on the Regulation of Emotion and on Functional Connectivity in the Brain

Science.gov (United States)

Golkar, Armita; Johansson, Emilia; Kasahara, Maki; Osika, Walter; Perski, Aleksander; Savic, Ivanka

2014-01-01

Despite mounting reports about the negative effects of chronic occupational stress on cognitive and emotional functions, the underlying mechanisms are unknown. Recent findings from structural MRI raise the question whether this condition could be associated with a functional uncoupling of the limbic networks and an impaired modulation of emotional stress. To address this, 40 subjects suffering from burnout symptoms attributed to chronic occupational stress and 70 controls were investigated using resting state functional MRI. The participants' ability to up- regulate, down-regulate, and maintain emotion was evaluated by recording their acoustic startle response while viewing neutral and negatively loaded images. Functional connectivity was calculated from amygdala seed regions, using explorative linear correlation analysis. Stressed subjects were less capable of down-regulating negative emotion, but had normal acoustic startle responses when asked to up-regulate or maintain emotion and when no regulation was required. The functional connectivity between the amygdala and the anterior cingulate cortex correlated with the ability to down-regulate negative emotion. This connectivity was significantly weaker in the burnout group, as was the amygdala connectivity with the dorsolateral prefrontal cortex and the motor cortex, whereas connectivity from the amygdala to the cerebellum and the insular cortex were stronger. In subjects suffering from chronic occupational stress, the functional couplings within the emotion- and stress-processing limbic networks seem to be altered, and associated with a reduced ability to down-regulate the response to emotional stress, providing a biological substrate for a further facilitation of the stress condition. PMID:25184294

Novel regulation of aquaporins during osmotic stress.

Science.gov (United States)

Vera-Estrella, Rosario; Barkla, Bronwyn J; Bohnert, Hans J; Pantoja, Omar

2004-08-01

Aquaporin protein regulation and redistribution in response to osmotic stress was investigated. Ice plant (Mesembryanthemum crystallinum) McTIP1;2 (McMIPF) mediated water flux when expressed in Xenopus leavis oocytes. Mannitol-induced water imbalance resulted in increased protein amounts in tonoplast fractions and a shift in protein distribution to other membrane fractions, suggesting aquaporin relocalization. Indirect immunofluorescence labeling also supports a change in membrane distribution for McTIP1;2 and the appearance of a unique compartment where McTIP1;2 is expressed. Mannitol-induced redistribution of McTIP1;2 was arrested by pretreatment with brefeldin A, wortmannin, and cytochalasin D, inhibitors of vesicle trafficking-related processes. Evidence suggests a role for glycosylation and involvement of a cAMP-dependent signaling pathway in McTIP1;2 redistribution. McTIP1;2 redistribution to endosomal compartments may be part of a homeostatic process to restore and maintain cellular osmolarity under osmotic-stress conditions.

Differential expression of genes regulated in response to drought stress in diploid cotton (Gossypium arboreum) (abstract)

International Nuclear Information System (INIS)

Hussain, T.; Majeed, A.; Maqbool, A.; Hussain, S.S.; Ali, T.; Riazuddin, S.

2005-01-01

Negative effects on the Water status of plants is one of the most common and deleterious stresses experienced by wild and cultivated plants throughout the World. Our project is designed to identify, clone and characterize gene sequences regulated in response to Water stress (e.g., drought). We used the differential-display reverse transcriptase polymerase chain reaction (DD-RT- PCA) methodology to accomplish our Objectives. Structural and functional characterization of environmental stress-induced genes has contributed to a better understanding of how plants respond and adapt to different abiotic stresses. Differential display was used to compare overall difference in gene expression between draught stressed and unstressed (control) plants of diploid Cotton (Gossypium arboreum). DDRT-PCR product from stressed and unstressed samples resolved side by side on 6% PAGE to compare qualitative and quantitative difference in mRNA expression. A total of 81 primer combinations were tested. DDRT -PCR enabled us to identify differentially expressed transcripts between water stressed and non-stressed cotton seedlings. PAGE revealed a total of 347 DNA transcripts in stressed samples (New Transcripts) while 110 down regulated and 209 up regulated DNA transcripts were also recorded. Similarly. 22 DNA transcripts were identified based on the comparative study of PAGE and Agarose gel electrophoresis. These sequences showed various degree homology With draught tolerant genes in the gene bank. (author)

Evolution of increased adult longevity in Drosophila melanogaster populations selected for adaptation to larval crowding.

Science.gov (United States)

Shenoi, V N; Ali, S Z; Prasad, N G

2016-02-01

In holometabolous animals such as Drosophila melanogaster, larval crowding can affect a wide range of larval and adult traits. Adults emerging from high larval density cultures have smaller body size and increased mean life span compared to flies emerging from low larval density cultures. Therefore, adaptation to larval crowding could potentially affect adult longevity as a correlated response. We addressed this issue by studying a set of large, outbred populations of D. melanogaster, experimentally evolved for adaptation to larval crowding for 83 generations. We assayed longevity of adult flies from both selected (MCUs) and control populations (MBs) after growing them at different larval densities. We found that MCUs have evolved increased mean longevity compared to MBs at all larval densities. The interaction between selection regime and larval density was not significant, indicating that the density dependence of mean longevity had not evolved in the MCU populations. The increase in longevity in MCUs can be partially attributed to their lower rates of ageing. It is also noteworthy that reaction norm of dry body weight, a trait probably under direct selection in our populations, has indeed evolved in MCU populations. To the best of our knowledge, this is the first report of the evolution of adult longevity as a correlated response of adaptation to larval crowding. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

On longevity and the aging process : a magnetic resonance imaging study of the brain

NARCIS (Netherlands)

Altmann-Schneider, Irmhild

2015-01-01

The aim of this thesis was to investigate the radiological phenotype of the human brain in familial longevity with regard to brain structure. This study was performed as part of the Leiden Longevity Study – a study population consisting of offspring of long-lived Dutch people who are genetically

Dietary regulation of hypodermal polyploidization in C. elegans

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Lozano Encarnación

2008-03-01

Full Text Available Abstract Background Dietary restriction (DR results in increased longevity, reduced fecundity and reduced growth in many organisms. Though many studies have examined the effects of DR on longevity and fecundity, few have investigated the effects on growth. Results Here we use Caenorhabditis elegans to determine the mechanisms that regulate growth under DR. We show that rather than a reduction in cell number, decreased growth in wild type C. elegans under DR is correlated with lower levels of hypodermal polyploidization. We also show that mutants lacking wild type sensory ciliated neurons are small, exhibit hypo-polyploidization and more importantly, when grown under DR, reduce their levels of endoreduplication to a lesser extent than wild type, suggesting that these neurons are required for the regulation of hypodermal polyploidization in response to DR. Similarly, we also show that the cGMP-dependent protein kinase EGL-4 and the SMA/MAB signalling pathway regulate polyploidization under DR. Conclusion We show C. elegans is capable of actively responding to food levels to regulate adult ploidy. We suggest this response is dependent on the SMA/MAB signalling pathway.

Solid lubricant mass contact transfer technology usage for vacuum ball bearings longevity increasing

Science.gov (United States)

Arzymatov, B.; Deulin, E.

2016-07-01

A contact mass transfer technological method of solid lubricant deposition on components of vacuum ball bearings is presented. Physics-mathematical model of process contact mass transfer is being considered. The experimental results of ball bearings covered with solid lubricant longevity in vacuum are presented. It is shown that solid lubricant of contact mass transfer method deposition is prospective for ball bearing longevity increasing.

Smiling is fun: a Coping with Stress and Emotion Regulation Program.

Science.gov (United States)

Botella, Cristina; Mira, Adriana; Garcia-Palacios, Azucena; Quero, Soledad; Navarro, Ma Vicenta; Riera López Del Amo, Antonio; Molinari, Guadalupe; Castilla, Diana; Moragrega, Inés; Soler, Carla; Alcañiz, Mariano; Baños, Rosa Maria

2012-01-01

Emotional disorders (Anxiety disorders and Mood disorders) are one of the most common health problems worldwide, and their economic costs are very high. People suffering from emotional disorders often use maladaptive emotion regulation strategies and have low coping behaviour that contributes to the presence of clinical symptoms. For this reason, it is important to develop strategies to monitor coping and promote emotion regulation in people exposed to high levels of stress. Information and Communication Technologies (ICT) can help us in this task. Recent systematic reviews of literature on evidence-based CBT treatments delivered via the Internet show that these approaches are effective. We have developed an intervention program ICT based: Coping with Stress and Emotion Regulation Program (Smiling is Fun), a self-applied program via the Internet. Smiling is Fun follows a transdiagnostic perspective, and it is based on CBT techniques. However, it also includes other psychological strategies to improve positive mood. The aim of the present work is to describe Smiling is Fun and the study designed to test its efficacy.

The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans.

Science.gov (United States)

Iannacone, Michael J; Beets, Isabel; Lopes, Lindsey E; Churgin, Matthew A; Fang-Yen, Christopher; Nelson, Matthew D; Schoofs, Liliane; Raizen, David M

2017-01-17

In response to environments that cause cellular stress, animals engage in sleep behavior that facilitates recovery from the stress. In Caenorhabditis elegans , stress-induced sleep(SIS) is regulated by cytokine activation of the ALA neuron, which releases FLP-13 neuropeptides characterized by an amidated arginine-phenylalanine (RFamide) C-terminus motif. By performing an unbiased genetic screen for mutants that impair the somnogenic effects of FLP-13 neuropeptides, we identified the gene dmsr-1 , which encodes a G-protein coupled receptor similar to an insect RFamide receptor. DMSR-1 is activated by FLP-13 peptides in cell culture, is required for SIS in vivo , is expressed non-synaptically in several wake-promoting neurons, and likely couples to a Gi/o heterotrimeric G-protein. Our data expand our understanding of how a single neuroendocrine cell coordinates an organism-wide behavioral response, and suggest that similar signaling principles may function in other organisms to regulate sleep during sickness.

Are adult life history traits in oriental fruit moth affected by a mild pupal heat stress?

Science.gov (United States)

Zheng, Jincheng; Cheng, Xiongbin; Hoffmann, Ary A; Zhang, Bo; Ma, Chun-Sen

2017-10-01

Thermal stress at one life stage can affect fitness at a later stage in ectotherms with complex life cycles. Most relevant studies have focused on extreme stress levels, but here we also show substantial fitness effects in a moth when pupae are exposed to a relatively mild and sublethal heat stress. We consider the impact of a 35°C heat stress of 2h in three geographically separate populations of the oriental fruit moth (OFM, Grapholita molesta) from northern, middle and southern China. Heat stress negatively affected fecundity but increased adult heat resistance and adult longevity. Fitness effects were mostly consistent across populations but there were also some population differences. In the Shenyang population from northern China, there was a hormetic effect of heat on female longevity not evident in the other populations. Adults from all populations had higher LT 50 s due to heat stress after pupal exposure to the sublethal stress. These results highlight that the pupal stage is a particularly sensitive window for development and they have implications for seasonal adaptation in uncertain environments as well as changes in pest dynamics under climate warming. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transcriptional profiling of human familial longevity indicates a role for ASF1A and IL7R.

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Willemijn M Passtoors

Full Text Available The Leiden Longevity Study consists of families that express extended survival across generations, decreased morbidity in middle-age, and beneficial metabolic profiles. To identify which pathways drive this complex phenotype of familial longevity and healthy aging, we performed a genome-wide gene expression study within this cohort to screen for mRNAs whose expression changes with age and associates with longevity. We first compared gene expression profiles from whole blood samples between 50 nonagenarians and 50 middle-aged controls, resulting in identification of 2,953 probes that associated with age. Next, we determined which of these probes associated with longevity by comparing the offspring of the nonagenarians (50 subjects and the middle-aged controls. The expression of 360 probes was found to change differentially with age in members of the long-lived families. In a RT-qPCR replication experiment utilizing 312 controls, 332 offspring and 79 nonagenarians, we confirmed a nonagenarian specific expression profile for 21 genes out of 25 tested. Since only some of the offspring will have inherited the beneficial longevity profile from their long-lived parents, the contrast between offspring and controls is expected to be weak. Despite this dilution of the longevity effects, reduced expression levels of two genes, ASF1A and IL7R, involved in maintenance of chromatin structure and the immune system, associated with familial longevity already in middle-age. The size of this association increased when controls were compared to a subfraction of the offspring that had the highest probability to age healthily and become long-lived according to beneficial metabolic parameters. In conclusion, an "aging-signature" formed of 21 genes was identified, of which reduced expression of ASF1A and IL7R marked familial longevity already in middle-age. This indicates that expression changes of genes involved in metabolism, epigenetic control and immune function

Effects of Repeated Stress on Age-Dependent GABAergic Regulation of the Lateral Nucleus of the Amygdala.

Science.gov (United States)

Zhang, Wei; Rosenkranz, J Amiel

2016-08-01

The adolescent age is associated with lability of mood and emotion. The onset of depression and anxiety disorders peaks during adolescence and there are differences in symptomology during adolescence. This points to differences in the adolescent neural circuitry that underlies mood and emotion, such as the amygdala. The human adolescent amygdala is more responsive to evocative stimuli, hinting to less local inhibitory regulation of the amygdala, but this has not been explored in adolescents. The amygdala, including the lateral nucleus (LAT) of the basolateral amygdala complex, is sensitive to stress. The amygdala undergoes maturational processes during adolescence, and therefore may be more vulnerable to harmful effects of stress during this time period. However, little is known about the effects of stress on the LAT during adolescence. GABAergic inhibition is a key regulator of LAT activity. Therefore, the purpose of this study was to test whether there are differences in the local GABAergic regulation of the rat adolescent LAT, and differences in its sensitivity to repeated stress. We found that LAT projection neurons are subjected to weaker GABAergic inhibition during adolescence. Repeated stress reduced in vivo endogenous and exogenous GABAergic inhibition of LAT projection neurons in adolescent rats. Furthermore, repeated stress decreased measures of presynaptic GABA function and interneuron activity in adolescent rats. In contrast, repeated stress enhanced glutamatergic drive of LAT projection neurons in adult rats. These results demonstrate age differences in GABAergic regulation of the LAT, and age differences in the mechanism for the effects of repeated stress on LAT neuron activity. These findings provide a substrate for increased mood lability in adolescents, and provide a substrate by which adolescent repeated stress can induce distinct behavioral outcomes and psychiatric symptoms.

Hyperosmotic stress regulates the distribution and stability of myocardin-related transcription factor, a key modulator of the cytoskeleton

DEFF Research Database (Denmark)

Ly, Donald L.; Waheed, Faiza; Lodyga, Monika

2013-01-01

Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin-regulated coactiv......Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin......-regulated coactivator of serum response factor, is a major link between the actin skeleton and transcriptional control. We therefore investigated whether MRTF is regulated by hyperosmotic stress. Here we show that hypertonicity induces robust, rapid, and transient translocation of MRTF from the cytosol to the nucleus...... in kidney tubular cells. We found that the hyperosmolarity-triggered MRTF translocation is mediated by the RhoA/Rho kinase (ROK) pathway. Moreover, the Rho guanine nucleotide exchange factor GEF-H1 is activated by hyperosmotic stress, and it is a key contributor to the ensuing RhoA activation and MRTF...

Tocopherol deficiency reduces sucrose export from salt-stressed potato leaves independently of oxidative stress and symplastic obstruction by callose

Science.gov (United States)

Asensi-Fabado, María Amparo; Ammon, Alexandra; Sonnewald, Uwe; Munné-Bosch, Sergi; Voll, Lars M.

2015-01-01

Tocopherol cyclase, encoded by the gene SUCROSE EXPORT DEFECTIVE1, catalyses the second step in the synthesis of the antioxidant tocopherol. Depletion of SXD1 activity in maize and potato leaves leads to tocopherol deficiency and a ‘sugar export block’ phenotype that comprises massive starch accumulation and obstruction of plasmodesmata in paraveinal tissue by callose. We grew two transgenic StSXD1:RNAi potato lines with severe tocopherol deficiency under moderate light conditions and subjected them to salt stress. After three weeks of salt exposure, we observed a strongly reduced sugar exudation rate and a lack of starch mobilization in leaves of salt-stressed transgenic plants, but not in wild-type plants. However, callose accumulation in the vasculature declined upon salt stress in all genotypes, indicating that callose plugging of plasmodesmata was not the sole cause of the sugar export block phenotype in tocopherol-deficient leaves. Based on comprehensive gene expression analyses, we propose that enhanced responsiveness of SnRK1 target genes in mesophyll cells and altered redox regulation of phloem loading by SUT1 contribute to the attenuation of sucrose export from salt-stressed SXD:RNAi source leaves. Furthermore, we could not find any indication that elevated oxidative stress may have served as a trigger for the salt-induced carbohydrate phenotype of SXD1:RNAi transgenic plants. In leaves of the SXD1:RNAi plants, sodium accumulation was diminished, while proline accumulation and pools of soluble antioxidants were increased. As supported by phytohormone contents, these differences seem to increase longevity and prevent senescence of SXD:RNAi leaves under salt stress. PMID:25428995

Economics and extended longevity: a case study.

Science.gov (United States)

Gori, G B; Richter, B J; Yu, W K

1984-07-01

Preventive and therapeutic advances have brought life expectancy in the United States to well over 70 years and have shifted mortality causes from acute to chronic diseases, the determinants of which are genetics, lifestyle, the environment, and aging itself. Plausible approaches to chronic disease prevention are likely to increase longevity further, with some foreseeable effects on demographic and economic projections. Primarily, longevity advances would swell forecasts of population size, and would thus have to be met by production advances in order to maintain or improve living standards. This study, a restricted example, considers the probable demographic and economic consequences of a limited prevention program in the context of the Ford Motor Company, based on actual experience and certain expectations up to the year 2000. According to the results, prevention would reduce outlays for life insurance, disability, and health care, but would also generate the higher costs of extending pension plans. Undoubtedly, prevention will continue to be highly ranked in society's pursuit of happiness, and society must prepare to meet its effects with appropriate social and economic policies.

The Prevalence of Longevity Among Leading Brands

Directory of Open Access Journals (Sweden)

Bradford T. Hudson

2014-10-01

Full Text Available The longevity of brands is embedded in scholarship involving brand processes that evolve over time such as brand equity, loyalty, nostalgia, and lifecycle. It is also an important conceptual element in the emerging topic of brand heritage. This paper offers new insight regarding the prevalence of brand longevity in a variety of industries, based on historical research about 148 leading brands ranked in prior studies by the consulting firm Interbrand. The author finds that a significant proportion (64 brands representing 43% of the total number are aged 100 years or more. The oldest brands are grouped in the food industry, while some of the youngest brands are grouped in the hospitality industry. The author applies the principles of scale and scope from the work of business historian Alfred Chandler to explain the timing of this industry emergence. The advanced age of many leading brands suggests the need for stewardship to preserve and protect the equity that resides in historic brands, and supports the argument that further attention should be directed toward the study of brand heritage effects.

Gender-specific association of ADA genetic polymorphism with human longevity.

Science.gov (United States)

Napolioni, Valerio; Lucarini, Nazzareno

2010-08-01

Aim of this study was to investigate whether the polymorphic ADA (Adenosine Deaminase, EC 3.5.4.4) gene, which determines the cellular level of adenosine and plays a crucial role in the regulation of the immune system and in the control of metabolic rates, is involved in longevity. 884 unrelated healthy individuals (age range 10-106 years, 400 males and 484 females) from central Italy were studied. ADA genotyping was performed by RFLP-PCR. Frequency distributions were compared using the chi-square test and a three-way contingency table analysis by a log linear model was applied to test independence between the variables. We found that ADA influences human life-span in a sex and age specific way. An increased frequency of ADA*2 carriers was found in males aged 80-85, and a decreased frequency in males over 85 (chi(2) = 13.93; df = 3; P = 0.003); significant differences among the age groups was not found in females. A strong interaction among age groups, ADA genotype and sex (G = 15.086; df = 3; P = 0.0017) was found. Males aged 80-85 could be protected from ischemic stroke by higher levels of adenosine (determined by the ADA*2 allele). The decrease of ADA*2 carriers in males over 85 may depend essentially on immunological factors; reduced levels of adenosine protect from asthma and other pulmonary diseases and lead to a reduced activation of inflammatory cells and pro-inflammatory cytokines production. Moreover, the low level of adenosine may potentiate the activity of NK and other cellular effectors against tumor cells. The negligible effect of ADA genetic polymorphism in females suggest a marginal influence of genetic factors in determining longevity in this sex, confirming previous reports.

The GH/IGF-1 axis in ageing and longevity

Science.gov (United States)

List, Edward O.; Berryman, Darlene E.; Murrey, John W.

2014-01-01

Secretion of growth hormone (GH), and consequently that of insulin-like growth factor 1 (IGF-1), declines over time until only low levels can be detected in individuals aged ≥60 years. This phenomenon, which is known as the ‘somatopause’, has led to recombinant human GH being widely promoted and abused as an antiageing drug, despite lack of evidence of efficacy. By contrast, several mutations that decrease the tone of the GH/IGF-1 axis are associated with extended longevity in mice. In humans, corresponding or similar mutations have been identified, but whether these mutations alter longevity has yet to be established. The powerful effect of reduced GH activity on lifespan extension in mice has generated the hypothesis that pharmaceutically inhibiting, rather than increasing, GH action might delay ageing. Moreover, mice as well as humans with reduced activity of the GH/IGF-1 axis are protected from cancer and diabetes mellitus, two major ageing-related morbidities. Here, we review data on mouse strains with alterations in the GH/IGF-1 axis and their effects on lifespan. The outcome of corresponding or similar mutations in humans is described, as well as the potential mechanisms underlying increased longevity and the therapeutic benefits and risks of medical disruption of the GH/IGF-1 axis in humans. PMID:23591370

Glutaredoxin 1 (GRX1) inhibits oxidative stress and apoptosis of chondrocytes by regulating CREB/HO-1 in osteoarthritis.

Science.gov (United States)

Sun, Jie; Wei, Xuelei; Lu, Yandong; Cui, Meng; Li, Fangguo; Lu, Jie; Liu, Yunjiao; Zhang, Xi

2017-10-01

GRX1 (glutaredoxin1), a sulfhydryl disulfide oxidoreductase, is involved in many cellular processes, including anti-oxidation, anti-apoptosis, and regulation of cell differentiation. However, the role of GRX1 in the oxidative stress and apoptosis of osteoarthritis chondrocytes remains unclear, prompting the current study. Protein and mRNA expressions were measured by Western blot and RT-qPCR. Oxidative stress was detected by the measurement of MDA and SOD contents. Cells apoptosis were detected by Annexin V-FITC/PI and caspase-3 activity assays. We found that the mRNA and protein expressions of GRX1 were significantly down-regulated in osteoarthritis tissues and cells. GRX1 overexpression increased the mRNA and protein expression of CREB and HO-1. Meanwhile, GRX1 overexpression inhibited oxidative stress and apoptosis in osteoarthritis chondrocytes. Furthermore, we found that GRX1 overexpression regulated HO-1 by increasing CREB, and that HO-1 regulated oxidative stress and apoptosis in osteoarthritis chondrocytes. Thus, GRX1 overexpression constrains oxidative stress and apoptosis in osteoarthritis chondrocytes by regulating CREB/HO-1, providing a novel insight into the molecular mechanism and potential treatment of osteoarthritis. Copyright © 2017. Published by Elsevier Ltd.

Prenatal Maternal Stress Programs Infant Stress Regulation

Science.gov (United States)

Davis, Elysia Poggi; Glynn, Laura M.; Waffarn, Feizal; Sandman, Curt A.

2011-01-01

Objective: Prenatal exposure to inappropriate levels of glucocorticoids (GCs) and maternal stress are putative mechanisms for the fetal programming of later health outcomes. The current investigation examined the influence of prenatal maternal cortisol and maternal psychosocial stress on infant physiological and behavioral responses to stress.…

Longevity of posterior resin composite restorations in permanent teeth in Public Dental Health Service

DEFF Research Database (Denmark)

Pallesen, Ulla; van Dijken, Jan W V; Halken, Jette

2013-01-01

To investigate in a prospective follow up the longevity of posterior resin composites (RC) placed in permanent teeth of children and adolescents attending Public Dental Health Service.......To investigate in a prospective follow up the longevity of posterior resin composites (RC) placed in permanent teeth of children and adolescents attending Public Dental Health Service....

Data Resources for Biodemographic Studies on Familial Clustering of Human Longevity

Directory of Open Access Journals (Sweden)

1999-09-01

Full Text Available The main cause that hampered many previous biodemographic studies of human longevity is the lack of appropriate data. At the same time, many existing data resources (millions of genealogical records are under-utilized, because their very existence is not widely known, let alone the quality and scientific value of these data sets are not yet validated. The purpose of this work is to review the data resources that could be used in familial studies of human longevity. This is an extended and supplemented version of the previous study made by the authors upon the request of the National Institute on Aging (1998 NIH Professional Service Contract. The review describes: (1 data resources developed for biodemographic studies, (2 data collected in the projects on historical demography, (3 data resources for long lived individuals and their families, (4 publicly available computerized genealogical data resources, (5 published genealogical and family history data. The review also contains the description of databases developed by the participants of the Research Workshops "Genes, Genealogies, and Longevity" organized by the Max Planck Institute for Demographic Research.

Stress axis regulation during social ascension in a group-living cichlid fish.

Science.gov (United States)

Culbert, Brett M; Gilmour, Kathleen M; Balshine, Sigal

2018-06-19

Animals living in groups often form social hierarchies, with characteristic behaviours and physiologies associated with rank. However, when social opportunities arise and a subordinate ascends into a dominant position, quick adjustments are necessary to secure this position. Such periods of social transition are typically associated with elevated glucocorticoid production, but the precise regulation of the stress axis during these occasions is not well understood. Using the group-living cichlid, Neolamprologus pulcher, the effects of social ascension on the stress axis were assessed. Ascenders rapidly filled experimentally created vacancies, adopting a dominant behavioural phenotype within 72 h-elevating aggression, activity, and workload, while receiving high rates of affiliative behaviours from their group members. Despite assuming behavioural dominance within their groups, ascenders displayed higher cortisol levels than dominants three days post-ascension. Additionally, compared to subordinates, ascenders had increased transcript abundance of steroidogenic acute regulatory protein (star) and cytochrome p450 side-chain cleavage enzyme (p450scc) in the head kidney, indicating activation of the stress axis. Cortisol levels were lowest in ascenders that displayed low rates of aggression, potentially reflecting the reestablishment of social stability in these groups. Increased transcript abundance of both glucocorticoid receptors (gr1 and gr2) in the brain's preoptic area (POA) of ascenders compared to dominants suggested an enhanced capacity for cortisol regulation via negative feedback. Our results reveal a regulatory cascade of behavioural and physiological interactions and highlight the importance of investigating the underlying mechanisms regulating the stress axis. Copyright © 2018. Published by Elsevier Inc.

Non-existence of Steady State Equilibrium in the Neoclassical Growth Model with a Longevity Trend

DEFF Research Database (Denmark)

Hermansen, Mikkel Nørlem

of steady state equilibrium when considering the empirically observed trend in longevity. We extend a standard continuous time overlapping generations model by a longevity trend and are thereby able to study the properties of mortality-driven population growth. This turns out to be exceedingly complicated...

Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

DEFF Research Database (Denmark)

Munk, Stephanie; Sigurðsson, Jón Otti; Xiao, Zhenyu

2017-01-01

The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM)-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essentia....... They analyze changes in the SUMO and phosphoproteome after MMC and hydroxyurea treatments and find that the DNA damage response kinases ATR and ATM globally regulate SUMOylation upon replication stress and fork breakage....

A Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stress

KAUST Repository

Ritho, Joan

2015-07-23

SUMOylation has been implicated in cellular stress adaptation, but its role in regulating liver kinase B1 (LKB1), a major upstream kinase of the energy sensor AMP-activated protein kinase (AMPK), is unknown. Here, we show that energy stress triggers an increase in SUMO1 modification of LKB1, despite a global reduction in both SUMO1 and SUMO2/3 conjugates. During metabolic stress, SUMO1 modification of LKB1 lysine 178 is essential in promoting its interaction with AMPK via a SUMO-interacting motif (SIM) essential for AMPK activation. The LKB1 K178R SUMO mutant had defective AMPK signaling and mitochondrial function, inducing death in energy-deprived cells. These results provide additional insight into how LKB1-AMPK signaling is regulated during energy stress, and they highlight the critical role of SUMOylation in maintaining the cell’s energy equilibrium.

A Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stress

KAUST Repository

Ritho, Joan; Arold, Stefan T.; Yeh, Edward  T.H.

2015-01-01

SUMOylation has been implicated in cellular stress adaptation, but its role in regulating liver kinase B1 (LKB1), a major upstream kinase of the energy sensor AMP-activated protein kinase (AMPK), is unknown. Here, we show that energy stress triggers an increase in SUMO1 modification of LKB1, despite a global reduction in both SUMO1 and SUMO2/3 conjugates. During metabolic stress, SUMO1 modification of LKB1 lysine 178 is essential in promoting its interaction with AMPK via a SUMO-interacting motif (SIM) essential for AMPK activation. The LKB1 K178R SUMO mutant had defective AMPK signaling and mitochondrial function, inducing death in energy-deprived cells. These results provide additional insight into how LKB1-AMPK signaling is regulated during energy stress, and they highlight the critical role of SUMOylation in maintaining the cell’s energy equilibrium.

Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress.

Science.gov (United States)

Glorieux, Christophe; Sandoval, Juan Marcelo; Fattaccioli, Antoine; Dejeans, Nicolas; Garbe, James C; Dieu, Marc; Verrax, Julien; Renard, Patricia; Huang, Peng; Calderon, Pedro Buc

2016-10-01

Regulation of ROS metabolism plays a major role in cellular adaptation to oxidative stress in cancer cells, but the molecular mechanism that regulates catalase, a key antioxidant enzyme responsible for conversion of hydrogen peroxide to water and oxygen, remains to be elucidated. Therefore, we investigated the transcriptional regulatory mechanism controlling catalase expression in three human mammary cell lines: the normal mammary epithelial 250MK primary cells, the breast adenocarcinoma MCF-7 cells and an experimental model of MCF-7 cells resistant against oxidative stress resulting from chronic exposure to H 2 O 2 (Resox), in which catalase was overexpressed. Here we identify a novel promoter region responsible for the regulation of catalase expression at -1518/-1226 locus and the key molecules that interact with this promoter and affect catalase transcription. We show that the AP-1 family member JunB and retinoic acid receptor alpha (RARα) mediate catalase transcriptional activation and repression, respectively, by controlling chromatin remodeling through a histone deacetylases-dependent mechanism. This regulatory mechanism plays an important role in redox adaptation to chronic exposure to H 2 O 2 in breast cancer cells. Our study suggests that cancer adaptation to oxidative stress may be regulated by transcriptional factors through chromatin remodeling, and reveals a potential new mechanism to target cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Rab from the white shrimp Litopenaeus vannamei: characterization and its regulation upon environmental stress.

Science.gov (United States)

Wang, Lei; Wang, Xiao-Rong; Liu, Jin; Chen, Chu-Xian; Liu, Yuan; Wang, Wei-Na

2015-10-01

With the destruction of the ecological environment, shrimp cultivation in China has been seriously affected by outbreaks of infectious diseases. Rab, which belong to small GTPase Ras superfamily, can regulate multiple steps in eukaryotic vesicle trafficking including vesicle budding, vesicle tethering, and membrane fusion. Knowledge of Rab in shrimp is essential to understanding regulation and detoxification mechanisms of environmental stress. In this study, we analyzed the functions of Rab from the Pacific white shrimp, Litopenaeus vannamei. Full-length cDNA of Rab was obtained, which was 751 bp long, with open reading frame encoding 206 amino acids. In this study, for the first time, the gene expression of Rab of L. vannamei was analyzed by quantitative real-time PCR after exposure to five kinds of environmental stresses (bacteria, pH, Cd, salinity and low temperature). The results demonstrate that Rab is sensitive and involved in bacteria, pH, and Cd stress responses and Rab is more sensitive to bacteria than other stresses. Therefore we infer that Rab may have relationship with the anti-stress mechanism induced by environment stress in shrimp and Rab could be used as critical biomarkers for environmental quality assessment.

The maize WRKY transcription factor ZmWRKY17 negatively regulates salt stress tolerance in transgenic Arabidopsis plants.

Science.gov (United States)

Cai, Ronghao; Dai, Wei; Zhang, Congsheng; Wang, Yan; Wu, Min; Zhao, Yang; Ma, Qing; Xiang, Yan; Cheng, Beijiu

2017-12-01

We cloned and characterized the ZmWRKY17 gene from maize. Overexpression of ZmWRKY17 in Arabidopsis led to increased sensitivity to salt stress and decreased ABA sensitivity through regulating the expression of some ABA- and stress-responsive genes. The WRKY transcription factors have been reported to function as positive or negative regulators in many different biological processes including plant development, defense regulation and stress response. This study isolated a maize WRKY gene, ZmWRKY17, and characterized its role in tolerance to salt stress by generating transgenic Arabidopsis plants. Expression of the ZmWRKY17 was up-regulated by drought, salt and abscisic acid (ABA) treatments. ZmWRKY17 was localized in the nucleus with no transcriptional activation in yeast. Yeast one-hybrid assay showed that ZmWRKY17 can specifically bind to W-box, and it can activate W-box-dependent transcription in planta. Heterologous overexpression of ZmWRKY17 in Arabidopsis remarkably reduced plant tolerance to salt stress, as determined through physiological analyses of the cotyledons greening rate, root growth, relative electrical leakage and malondialdehyde content. Additionally, ZmWRKY17 transgenic plants showed decreased sensitivity to ABA during seed germination and early seedling growth. Transgenic plants accumulated higher content of ABA than wild-type (WT) plants under NaCl condition. Transcriptome and quantitative real-time PCR analyses revealed that some stress-related genes in transgenic seedlings showed lower expression level than that in the WT when treated with NaCl. Taken together, these results suggest that ZmWRKY17 may act as a negative regulator involved in the salt stress responses through ABA signalling.

Effect of gamma irradiation on larval longevity of Chironomus Riparius Meigen. Vol. 4

International Nuclear Information System (INIS)

Samira, A.A.; El-Halfawy, N.; El-Ebiarie, A.S.

1996-01-01

Whole body irradiation is known to shorten the life-span of insects. This is further investigated in aquatic insect larvae, as part of a programme concerned with stress responses on these larvae. The effect of gamma rays on the longevity of different larval instars of midge Chironomus Riparius was investigated by using five doses of 1, 9, 30, 200 and 1000 Gy of gamma rays. Lt 50 (the time in days required for killing 50% of the population) was estimated using spss x programme. Data showed that irradiation decreased Lt 50 in the second, third and fourth instars in comparison to their control, while in the first instar, irradiation increased Lt 50 for all doses used. Shortening or increasing life was independent of the dose. Results were explained in terms of possibility of inhibition of enzymes. 1 fig., 1 tab

Longevity extension of worker honey bees (Apis mellifera) by royal jelly: optimal dose and active ingredient

OpenAIRE

Yang, Wenchao; Tian, Yuanyuan; Han, Mingfeng; Miao, Xiaoqing

2017-01-01

In the Western honey bee, Apis mellifera, queens and workers have different longevity although they share the same genome. Queens consume royal jelly (RJ) as the main food throughout their life, including as adults, but workers only eat worker jelly when they are larvae less than 3 days old. In order to explore the effect of RJ and the components affecting longevity of worker honey bees, we first determined the optimal dose for prolonging longevity of workers as 4% RJ in 50% sucrose solution,...

A prospective clinical evaluation of the longevity of resorbable ...

African Journals Online (AJOL)

2012-09-15

Sep 15, 2012 ... Key words: Evaluation, longevity, oral, resorbable sutures, surgical procedure. Date of ... presence of saliva, specific microbiota, high vascularization, as well as its ..... documented the mean survival of vicryl in the oral cavity.

ProBDNF Signaling Regulates Depression-Like Behaviors in Rodents under Chronic Stress.

Science.gov (United States)

Bai, Yin-Yin; Ruan, Chun-Sheng; Yang, Chun-Rui; Li, Jia-Yi; Kang, Zhi-Long; Zhou, Li; Liu, Dennis; Zeng, Yue-Qing; Wang, Ting-Hua; Tian, Chang-Fu; Liao, Hong; Bobrovskaya, Larisa; Zhou, Xin-Fu

2016-11-01

Chronic exposure to stressful environment is a key risk factor contributing to the development of depression. However, the mechanisms involved in this process are still unclear. Brain-derived neurotropic factor (BDNF) has long been investigated for its positive role in regulation of mood, although the role of its precursor, proBDNF, in regulation of mood is not known. In this study, using an unpredictable chronic mild stress (UCMS) paradigm we found that the protein levels of proBDNF were increased in the neocortex and hippocampus of stressed mice and this UCMS-induced upregulation of proBDNF was abolished by chronic administration of fluoxetine. We then established a rat model of UCMS and found that the expression of proBDNF/p75 NTR /sortilin was upregulated, whereas the expression of mature BDNF and TrkB was downregulated in both neocortex and hippocampus of chronically stressed rats. Finally, we found that the injection of anti-proBDNF antibody via intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) approaches into the UCMS rats significantly reversed the stress-induced depression-like behavior and restored the exploratory activity and spine growth. Although intramuscular injection of AAV-proBDNF did not exacerbate the UCMS-elicited rat mood-related behavioral or pathological abnormalities, i.c.v. injection of AAV-proBDNF increased the depression-like behavior in naive rats. Our findings suggest that proBDNF plays a role in the development of chronic stress-induced mood disturbances in rodents. Central (i.c.v.) or peripheral (i.p.) inhibition of proBDNF by injecting specific anti-proBDNF antibodies may provide a novel therapeutic approach for the treatment of stress-related mood disorders.

Reactive oxygen species, health and longevity

OpenAIRE

Vittorio Emanuele Bianchi; Giancarlo Falcioni

2016-01-01

Reactive oxygen species (ROS) are considered responsible of ageing in animal and humans. Mitochondria are both source and target of ROS. Various strategies to reduce ROS production have been considered to extend lifespan. Caloric restriction, exercise, and antioxidants are thought to be able to protect cells from structural and functional damage. However, there is evidence that ROS production has a detrimental effect on health, but at physiological levels are necessary to stimulate longevity....

L-Plastin promotes podosome longevity and supports macrophage motility

Science.gov (United States)

Zhou, Julie Y.; Szasz, Taylor P.; Stewart-Hutchinson, Phillip J.; Sivapalan, Janardan; Todd, Elizabeth M.; Deady, Lauren E.; Cooper, John A.; Onken, Michael D.; Morley, S. Celeste

2016-01-01

Elucidating the molecular regulation of macrophage migration is essential for understanding the patho-physiology of multiple human diseases, including host responses to infection and autoimmune disorders. Macrophage migration is supported by dynamic rearrangements of the actin cytoskeleton, with formation of actin-based structures such as podosomes and lamellipodia. Here we provide novel insights into the function of the actin-bundling protein l-plastin (LPL) in primary macrophages. We found that podosome stability is disrupted in primary resident peritoneal macrophages from LPL−/− mice. Live-cell imaging of F-actin using resident peritoneal macrophages from LifeACT-RFP+ mice demonstrated that loss of LPL led to decreased longevity of podosomes, without reducing the number of podosomes initiated. Additionally, macrophages from LPL−/− mice failed to elongate in response to chemotactic stimulation. These deficiencies in podosome stabilization and in macrophage elongation correlated with impaired macrophage transmigration in culture and decreased monocyte migration into murine peritoneum. Thus, we have identified a role for LPL in stabilizing long-lived podosomes and in enabling macrophage motility. PMID:27614263

Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells.

Science.gov (United States)

Fonseca, Sonya G; Ishigaki, Shinsuke; Oslowski, Christine M; Lu, Simin; Lipson, Kathryn L; Ghosh, Rajarshi; Hayashi, Emiko; Ishihara, Hisamitsu; Oka, Yoshitomo; Permutt, M Alan; Urano, Fumihiko

2010-03-01

Wolfram syndrome is an autosomal-recessive disorder characterized by insulin-dependent diabetes mellitus, caused by nonautoimmune loss of beta cells, and neurological dysfunctions. We have previously shown that mutations in the Wolfram syndrome 1 (WFS1) gene cause Wolfram syndrome and that WFS1 has a protective function against ER stress. However, it remained to be determined how WFS1 mitigates ER stress. Here we have shown in rodent and human cell lines that WFS1 negatively regulates a key transcription factor involved in ER stress signaling, activating transcription factor 6alpha (ATF6alpha), through the ubiquitin-proteasome pathway. WFS1 suppressed expression of ATF6alpha target genes and repressed ATF6alpha-mediated activation of the ER stress response element (ERSE) promoter. Moreover, WFS1 stabilized the E3 ubiquitin ligase HRD1, brought ATF6alpha to the proteasome, and enhanced its ubiquitination and proteasome-mediated degradation, leading to suppression of ER stress signaling. Consistent with these data, beta cells from WFS1-deficient mice and lymphocytes from patients with Wolfram syndrome exhibited dysregulated ER stress signaling through upregulation of ATF6alpha and downregulation of HRD1. These results reveal a role for WFS1 in the negative regulation of ER stress signaling and in the pathogenesis of diseases involving chronic, unresolvable ER stress, such as pancreatic beta cell death in diabetes.

A plant microRNA regulates the adaptation of roots to drought stress

KAUST Repository

Chen, Hao

2012-06-01

Plants tend to restrict their horizontal root proliferation in response to drought stress, an adaptive response mediated by the phytohormone abscisic acid (ABA) in antagonism with auxin through unknown mechanisms. Here, we found that stress-regulated miR393-guided cleavage of the transcripts encoding two auxin receptors, TIR1 and AFB2, was required for inhibition of lateral root growth by ABA or osmotic stress. Unlike in the control plants, the lateral root growth of seedlings expressing miR393-resistant TIR1 or AFB2 was no longer inhibited by ABA or osmotic stress. Our results indicate that miR393-mediated attenuation of auxin signaling modulates root adaptation to drought stress. © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Plant growth regulators ameliorate or exacerbate abiotic and biotic stress effects on Zea mays kernel weight in a genotype-specific manner

OpenAIRE

Wang, Yishi; Stutts, Lauren; Stapleton, Ann

2016-01-01

Plant growth regulators have documented roles in plant responses to single stresses. In combined-stress environments, plants display novel genetic architecture for growth traits and the response to growth regulators is unclear. We investigated the role of plant growth regulators in combined-stress responses in Zea mays. Twelve maize inbreds were exposed to all combinations of the following stressors: drought, nitrogen, and density stress. Chemical treatments were utilized to alter balances of...

Stress, self-regulation, and context: Evidence from the Health and Retirement Survey.

Science.gov (United States)

Mezuk, Briana; Ratliff, Scott; Concha, Jeannie B; Abdou, Cleopatra M; Rafferty, Jane; Lee, Hedwig; Jackson, James S

2017-12-01

Health-related behaviors, such as smoking, alcohol use, exercise, and diet, are major determinants of physical health and health disparities. However, a growing body of experimental research in humans and animals also suggests these behaviors can impact the ways our bodies respond to stress, such that they modulate (that is, serve as a means to self-regulate or cope with) the deleterious impact of stressful experiences on mental health. A handful of epidemiologic studies have investigated the intersection between stress and health behaviors on health disparities (both mental and physical), with mixed results. In this study we use a novel instrument designed to explicitly measure the self-regulatory motivations and perceived effectiveness of eight health-related self-regulatory behaviors (smoking, alcohol, drug use, overeating, prayer, exercise, social support, talking with a councilor) in a subset of the Health and Retirement Study (N=1,354, Mean age=67, 54% female). We find that these behaviors are commonly endorsed as self-regulatory stress-coping strategies, with prayer, social support, exercise, and overeating used most frequently. The likelihood of using particular behaviors as self-regulatory strategies varied significantly by sex, but not by race/ethnicity, education, or wealth. We also find that greater stress exposure is associated with higher likelihood of using these behaviors to self-regulate feelings of emotional distress, particularly health-harming behaviors like smoking, alcohol, and overeating. These findings provide an important link between sociological and psychological theoretical models on stress and empirical epidemiological research on social determinants of health and health disparities.

Stress, self-regulation, and context: Evidence from the health and retirement survey

Directory of Open Access Journals (Sweden)

Briana Mezuk

2017-12-01

Full Text Available Health-related behaviors, such as smoking, alcohol use, exercise, and diet, are major determinants of physical health and health disparities. However, a growing body of experimental research in humans and animals also suggests these behaviors can impact the ways our bodies respond to stress, such that they modulate (that is, serve as a means to self-regulate or cope with the deleterious impact of stressful experiences on mental health. A handful of epidemiologic studies have investigated the intersection between stress and health behaviors on health disparities (both mental and physical, with mixed results. In this study we use a novel instrument designed to explicitly measure the self-regulatory motivations and perceived effectiveness of eight health-related self-regulatory behaviors (smoking, alcohol, drug use, overeating, prayer, exercise, social support, talking with a counselor in a subset of the Health and Retirement Study (N=1354, Mean age=67, 54% female. We find that these behaviors are commonly endorsed as self-regulatory stress-coping strategies, with prayer, social support, exercise, and overeating used most frequently. The likelihood of using particular behaviors as self-regulatory strategies varied significantly by sex, with only limited variation by race/ethnicity, education, or wealth. We also find that greater stress exposure is associated with higher likelihood of using these behaviors to self-regulate feelings of emotional distress, particularly health-harming behaviors like smoking, alcohol, and overeating. These findings provide an important link between sociological and psychological theoretical models on stress and empirical epidemiological research on social determinants of health and health disparities.

Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity.

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Seals, Douglas R; Justice, Jamie N; LaRocca, Thomas J

2016-04-15

Most nations of the world are undergoing rapid and dramatic population ageing, which presents great socio-economic challenges, as well as opportunities, for individuals, families, governments and societies. The prevailing biomedical strategy for reducing the healthcare impact of population ageing has been 'compression of morbidity' and, more recently, to increase healthspan, both of which seek to extend the healthy period of life and delay the development of chronic diseases and disability until a brief period at the end of life. Indeed, a recently established field within biological ageing research, 'geroscience', is focused on healthspan extension. Superimposed on this background are new attitudes and demand for 'optimal longevity' - living long, but with good health and quality of life. A key obstacle to achieving optimal longevity is the progressive decline in physiological function that occurs with ageing, which causes functional limitations (e.g. reduced mobility) and increases the risk of chronic diseases, disability and mortality. Current efforts to increase healthspan centre on slowing the fundamental biological processes of ageing such as inflammation/oxidative stress, increased senescence, mitochondrial dysfunction, impaired proteostasis and reduced stress resistance. We propose that optimization of physiological function throughout the lifespan should be a major emphasis of any contemporary biomedical policy addressing global ageing. Effective strategies should delay, reduce in magnitude or abolish reductions in function with ageing (primary prevention) and/or improve function or slow further declines in older adults with already impaired function (secondary prevention). Healthy lifestyle practices featuring regular physical activity and ideal energy intake/diet composition represent first-line function-preserving strategies, with pharmacological agents, including existing and new pharmaceuticals and novel 'nutraceutical' compounds, serving as potential

Selection bias in studies of human reproduction-longevity trade-offs.

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Helle, Samuli

2017-12-13

A shorter lifespan as a potential cost of high reproductive effort in humans has intrigued researchers for more than a century. However, the results have been inconclusive so far and despite strong theoretical expectations we do not currently have compelling evidence for the longevity costs of reproduction. Using Monte Carlo simulation, it is shown here that a common practice in human reproduction-longevity studies using historical data (the most relevant data sources for this question), the omission of women who died prior to menopausal age from the analysis, results in severe underestimation of the potential underlying trade-off between reproduction and lifespan. In other words, assuming that such a trade-off is expressed also during reproductive years, the strength of the trade-off between reproduction and lifespan is progressively weakened when women dying during reproductive ages are sequentially and non-randomly excluded from the analysis. In cases of small sample sizes (e.g. few hundreds of observations), this selection bias by reducing statistical power may even partly explain the null results commonly found in this field. Future studies in this field should thus apply statistical approaches that account for or avoid selection bias in order to recover reliable effect size estimates between reproduction and longevity. © 2017 The Author(s).

Burial increases seed longevity of two Artemisia tridentata (Asteraceae) subspecies

Science.gov (United States)

Wijayratne, Upekala C.; Pyke, David A.

2012-01-01

Premise of the study: Seed longevity and persistence in soil seed banks may be especially important for population persistence in ecosystems where opportunities for seedling establishment and disturbance are unpredictable. The fire regime, an important driver of population dynamics in sagebrush steppe ecosystems, has been altered by exotic annual grass invasion. Soil seed banks may play an active role in postfire recovery of the foundation shrub Artemisia tridentata, yet conditions under which seeds persist are largely unknown. Methods: We investigated seed longevity of two Artemisia tridentata subspecies in situ by retrieving seed bags that were placed at varying depths over a 2 yr period. We also sampled naturally dispersed seeds in litter and soil immediately after seed dispersal and before flowering in subsequent seasons to estimate seed persistence. Key results: After 24 mo, seeds buried at least 3 cm below the soil surface retained 30–40% viability whereas viability of seeds on the surface and under litter declined to 0 and Artemisia tridentata has the potential to form a short-term soil seed bank that persists longer than has been commonly assumed, and that burial is necessary for seed longevity. Use of seeding techniques that promote burial of some seeds to aid in formation of a soil seed bank may increase restoration potential.

Fecundity and longevity of Bactrocera carambolae Drew & Hancock (Diptera: Tephritidae

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Cristiane Ramos Jesus-Barros

2017-12-01

Full Text Available Bactrocera carambolae Drew & Hancock is an exotic species considered a quarantine pest in Brazil, with distribution limited to the states of Amapá and Roraima. Knowledge of its biology under Brazilian conditions is still limited. The objective of this work was to determine the fecundity and longevity of B. carambolae females, reared on artificial diet, under laboratory conditions. The experiment was carried out at Embrapa Amapá, where 20 newly emerged B. carambolae couples were selected (F3 generation. Each couple was placed in a plastic cage containing feed, distilled water and an artificial oviposition device and stored in an air-conditioned room (26 ± 1°C, 60 ± 10% R. H. and 12-hour photoperiod. The eggs deposited on each device were counted daily. Mean survival was 90.70 ± 9.97 days and the maximum longevity was 150 days. The mean duration of the pre-oviposition period was 25.15 ± 3.54 days and the oviposition period was 62.73 ± 7.84 days. Fecundity was variable over time, with an oviposition peak on the 28th day. The mean number of eggs per female was 1,088.26 ± 167.82. These results suggest that B. carambolae uses high fecundity and longevity as a reproductive strategy.

H3K36 Methylation Regulates Nutrient Stress Response in Saccharomyces cerevisiae by Enforcing Transcriptional Fidelity

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Stephen L. McDaniel

2017-06-01

Full Text Available Set2-mediated histone methylation at H3K36 regulates diverse activities, including DNA repair, mRNA splicing, and suppression of inappropriate (cryptic transcription. Although failure of Set2 to suppress cryptic transcription has been linked to decreased lifespan, the extent to which cryptic transcription influences other cellular functions is poorly understood. Here, we uncover a role for H3K36 methylation in the regulation of the nutrient stress response pathway. We found that the transcriptional response to nutrient stress was dysregulated in SET2-deleted (set2Δ cells and was correlated with genome-wide bi-directional cryptic transcription that originated from within gene bodies. Antisense transcripts arising from these cryptic events extended into the promoters of the genes from which they arose and were associated with decreased sense transcription under nutrient stress conditions. These results suggest that Set2-enforced transcriptional fidelity is critical to the proper regulation of inducible and highly regulated transcription programs.

Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

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Petrie, Michael A; Kimball, Amy L; McHenry, Colleen L; Suneja, Manish; Yen, Chu-Ling; Sharma, Arpit; Shields, Richard K

2016-01-01

Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat) and mechanical stress (vibration) on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction. The purpose of this study is to examine whether active mechanical stress (muscle contraction), passive mechanical stress (vibration), or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair. Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI) participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus) to analyze mRNA gene expression. We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold), PGC-1α (5.46 fold), and ABRA (5.98 fold); and repressed MSTN (0.56 fold). Heat stress repressed PGC-1α (0.74 fold change; p muscle contraction. Vibration induced FOXK2 (p muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell development, growth, and repair.

AKT1 fails to replicate as a longevity-associated gene in Danish and German nonagenarians and centenarians

DEFF Research Database (Denmark)

Nygaard, Marianne; Soerensen, Mette; Flachsbart, Friederike

2013-01-01

In addition to APOE and FOXO3, AKT1 has recently been suggested as a third consistent longevity gene, with variants in AKT1 found to be associated with human lifespan in two previous studies. Here, we evaluated AKT1 as a longevity-associated gene across populations by attempting to replicate the ...... not support AKT1 as a universal longevity-associated gene.European Journal of Human Genetics advance online publication, 29 August 2012; doi:10.1038/ejhg.2012.196....

Childhood development and adult longevity in an archaeological population from Barton-upon-Humber, Lincolnshire, England.

Science.gov (United States)

Watts, Rebecca

2013-06-01

Changing patterns of stress indicators were used to examine the impact of external biocultural changes on childhood development and to explore the association between developmental health and adult longevity in a small market town in Lincolnshire, England. Cribra orbitalia, linear enamel hypoplasias (LEH), vertebral neural canal (VNC) size, craniofacial fluctuating asymmetry and femoral length were recorded in 267 adult skeletons dating from an earlier agricultural community (n=157) (AD1150-1700) and a later urbanised, middle-class community (n=110) (AD1700-1855) buried at St. Peter's Church, Barton-upon-Humber. The only stress indicator to display a statistical difference between periods was VNC size, which increased significantly in AD1700-1855. Analysis of stress indicators according to adult age-at-death revealed that cribra orbitalia, small VNC diameter and short femoral length in males and cribra orbitalia and craniofacial asymmetry in females were associated with a younger age-at-death in AD1150-1700. During AD1700-1855 both sexes showed selectivity for small VNC size. This demonstrates that external biocultural changes at Barton-upon-Humber had limited impact on growth, but did alter the long term sequelae of health insults experienced during childhood development. Copyright © 2013 Elsevier Inc. All rights reserved.

Perfectionism related to self-reported insomnia severity, but not when controlled for stress and emotion regulation

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Br

2015-02-01

Full Text Available Serge Brand,1,2 Roumen Kirov,3 Nadeem Kalak,1 Markus Gerber,2 Uwe Pühse,2 Sakari Lemola,4 Christoph U Correll,5 Samuele Cortese,6–8 Till Meyer,1 Edith Holsboer-Trachsler1 1Psychiatric Clinics of the University of Basel, Center for Affective, Stress and Sleep Disorders (ZASS, Basel, Switzerland; 2Department of Sport, Exercise and Health, Division of Sport Science, University of Basel, Basel, Switzerland; 3Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria; 4Faculty of Psychology, University of Basel, Basel, Switzerland; 5Division of Psychiatric Research, North Shore – Long Island Jewish Health System, Zucker Hillside Hospital, NY, USA; 6School of Medicine, University of Nottingham UK; 7Centre for ADHD and Neuro-developmental Disorders Across Lifespan, Institute of Mental Health, University of Nottingham UK; 8New York University Child Study Centre, New York, NY, USA Background: Perfectionism is understood as a set of personality traits such as unrealistically high and rigid standards for performance, fear of failure, and excessive self-criticism. Previous studies showed a direct association between increased perfectionism and poor sleep, though without taking into account possible mediating factors. Here, we tested the hypothesis that perfectionism was directly associated with poor sleep, and that this association collapsed, if mediating factors such as stress and poor emotion regulation were taken into account. Methods: Three hundred and forty six young adult students (M=23.87 years completed questionnaires relating to perfectionism traits, sleep, and psychological functioning such as stress perception, coping with stress, emotion regulation, and mental toughness. Results: Perfectionism was directly associated with poor sleep and poor psychological functioning. When stress, poor coping, and poor emotion regulation were entered in the equation, perfectionism traits no longer contributed substantively to the explanation

DRD4 genotype predicts longevity in mouse and human.

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Grady, Deborah L; Thanos, Panayotis K; Corrada, Maria M; Barnett, Jeffrey C; Ciobanu, Valentina; Shustarovich, Diana; Napoli, Anthony; Moyzis, Alexandra G; Grandy, David; Rubinstein, Marcelo; Wang, Gene-Jack; Kawas, Claudia H; Chen, Chuansheng; Dong, Qi; Wang, Eric; Volkow, Nora D; Moyzis, Robert K

2013-01-02

Longevity is influenced by genetic and environmental factors. The brain's dopamine system may be particularly relevant, since it modulates traits (e.g., sensitivity to reward, incentive motivation, sustained effort) that impact behavioral responses to the environment. In particular, the dopamine D4 receptor (DRD4) has been shown to moderate the impact of environments on behavior and health. We tested the hypothesis that the DRD4 gene influences longevity and that its impact is mediated through environmental effects. Surviving participants of a 30-year-old population-based health survey (N = 310; age range, 90-109 years; the 90+ Study) were genotyped/resequenced at the DRD4 gene and compared with a European ancestry-matched younger population (N = 2902; age range, 7-45 years). We found that the oldest-old population had a 66% increase in individuals carrying the DRD4 7R allele relative to the younger sample (p = 3.5 × 10(-9)), and that this genotype was strongly correlated with increased levels of physical activity. Consistent with these results, DRD4 knock-out mice, when compared with wild-type and heterozygous mice, displayed a 7-9.7% decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment. These results support the hypothesis that DRD4 gene variants contribute to longevity in humans and in mice, and suggest that this effect is mediated by shaping behavioral responses to the environment.

Proteomics of red and white corolla limbs in petunia reveals a novel function of the anthocyanin regulator ANTHOCYANIN1 in determining flower longevity.

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Prinsi, Bhakti; Negri, Alfredo S; Quattrocchio, Francesca M; Koes, Ronald E; Espen, Luca

2016-01-10

The Petunia hybrida ANTHOCYANIN1 (AN1) gene encodes a transcription factor that regulates both the expression of genes involved in anthocyanin synthesis and the acidification of the vacuolar lumen in corolla epidermal cells. In this work, the comparison between the red flowers of the R27 line with the white flowers of the isogenic an1 mutant line W225 showed that the AN1 gene has further pleiotropic effects on flavonoid biosynthesis as well as on distant physiological traits. The proteomic profiling showed that the an1 mutation was associated to changes in accumulation of several proteins, affecting both anthocyanin synthesis and primary metabolism. The flavonoid composition study confirmed that the an1 mutation provoked a broad attenuation of the entire flavonoid pathway, probably by indirect biochemical events. Moreover, proteomic changes and variation of biochemical parameters revealed that the an1 mutation induced a delay in the onset of flower senescence in W225, as supported by the enhanced longevity of the W225 flowers in planta and the loss of sensitivity of cut flowers to sugar. This study suggests that AN1 is possibly involved in the perception and/or transduction of ethylene signal during flower senescence. Copyright © 2015 Elsevier B.V. All rights reserved.

Study Protocol for the Preschooler Regulation of Emotional Stress (PRES Procedure

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Livio Provenzi

2017-09-01

Full Text Available Background: Emotional stress regulation (ESR rapidly develops during the first months of age and includes different behavioral strategies which largely contribute to children’s behavioral and emotional adjustment later in life. The assessment of ESR during the first years of life is critical to identify preschool children who are at developmental risk. Although ESR is generally included in larger temperament batteries [e.g., the Laboratory Temperament Assessment Battery (Lab-TAB], there is no standardized observational procedure to specifically assess and measure ESR in preschool aged children.Aim: Here, we describe the development of an observational procedure to assess ESR in preschool aged children [i.e., the Preschooler Regulation of Emotional Stress (PRES Procedure] and the related coding system.Methods: Four Lab-TAB emotional stress episodes (i.e., the Stranger, the Perfect Circle, the Missing Sticker, and the Transparent Box have been selected. Independent coders developed a list of ESR codes resulting in two general indexes (i.e., active engagement and stress level and five specific indexes (i.e., anger, control, fear, inhibition, sadness. Finally, specific actions have been planned to assess the validity and the coding system reliability of PRES procedure.Ethics and Dissemination: The study has been approved by the Ethical Committee of the Scientific Institute IRCCS Eugenio Medea, Bosisio Parini (Italy. The PRES validation and reliability assessment as well as its use with healthy and at-risk populations of preschool children will be object of future scientific publications and international conference presentations.

Phenotypic plasticity and longevity in plants and animals: cause and ...

Indian Academy of Sciences (India)

Prakash

not necessarily mutually exclusive theories to explain this extreme longevity, especially from the perspective of ... How density-dependent phenomena affecting the establishment .... shortening at each doubling event; telomerase activity.

Limitations and risks of meta-analyses of longevity studies

DEFF Research Database (Denmark)

Sebastiani, Paola; Bae, Harold; Gurinovich, Anastasia

2017-01-01

Searching for genetic determinants of human longevity has been challenged by the rarity of data sets with large numbers of individuals who have reached extreme old age, inconsistent definitions of the phenotype, and the difficulty of defining appropriate controls. Meta-analysis - a statistical...... method to summarize results from different studies - has become a common tool in genetic epidemiology to accrue large sample sizes for powerful genetic association studies. In conducting a meta-analysis of studies of human longevity however, particular attention must be made to the definition of cases...... and controls (including their health status) and on the effect of possible confounders such as sex and ethnicity upon the genetic effect to be estimated. We will show examples of how a meta-analysis can inflate the false negative rates of genetic association studies or it can bias estimates of the association...

The association between adult mortality risk and family history of longevity: the moderating effects of socioeconomic status.

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Temby, Owen F; Smith, Ken R

2014-11-01

Studies consistently show that increasing levels of socioeconomic status (SES) and having a familial history of longevity reduce the risk of mortality. But do these two variables interact, such that individuals with lower levels of SES, for example, may experience an attenuated longevity penalty by virtue of having long-lived relatives? This article examines this interaction by analysing survival past age 40 based on data from the Utah Population Database on an extinct cohort of men born from the years 1840 to 1909. Cox proportional hazards regression and logistic regression are used to test for the main and interaction mortality effects of SES and familial excess longevity (FEL), a summary measure of an individual's history of longevity among his or her relatives. This research finds that the mortality hazard rate for men in the top 15th percentile of occupational status decreases more as FEL increases than it does among men in the bottom 15th percentile. In addition, the mortality hazard rate among farmers decreases more as FEL increases than it does for non-farmers. With a strong family history of longevity as a proxy for a genetic predisposition, this research suggests that a gene-environment interaction occurs whereby the benefits of familial excess longevity are more available to those who have occupations with more autonomy and greater economic resources and/or opportunities for physical activity.

Acute Psychosocial Stress and Emotion Regulation Skills Modulate Empathic Reactions to Pain in Others

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Gabriele eBuruck

2014-05-01

Full Text Available Psychosocial stress affects resources for adequate coping with environmental demands. A crucial question in this context is the extent to which acute psychosocial stressors impact empathy and emotion regulation. In the present study, 120 participants were randomly assigned to a control group vs. a group confronted with the Trier Social Stress Test, an established paradigm for the induction of acute psychosocial stress. Empathy for pain as a specific subgroup of empathy was assessed via pain intensity ratings during a pain-picture task. Self-reported emotion regulation skills were measured as predictors using an established questionnaire. Stressed individuals scored significantly lower on the appraisal of pain pictures. A regression model was chosen to find variables that further predict the pain ratings. These findings implicate that acute psychosocial stress might impair empathic processes to observed pain in another person and the ability to accept one’s emotion additionally predicts the empathic reaction. Furthermore, the ability to tolerate negative emotions modulated the relation between stress and pain judgments, and thus influenced core cognitive-affective functions relevant for coping with environmental challenges. In conclusion, our study emphasizes the necessity of reducing negative emotions in terms of empathic distress when confronted with pain of another person under psychosocial stress, in order to be able to retain pro-social behavior.

Co-chaperone p23 regulates C. elegans Lifespan in Response to Temperature.

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Makoto Horikawa

2015-04-01

Full Text Available Temperature potently modulates various physiologic processes including organismal motility, growth rate, reproduction, and ageing. In ectotherms, longevity varies inversely with temperature, with animals living shorter at higher temperatures. Thermal effects on lifespan and other processes are ascribed to passive changes in metabolic rate, but recent evidence also suggests a regulated process. Here, we demonstrate that in response to temperature, daf-41/ZC395.10, the C. elegans homolog of p23 co-chaperone/prostaglandin E synthase-3, governs entry into the long-lived dauer diapause and regulates adult lifespan. daf-41 deletion triggers constitutive entry into the dauer diapause at elevated temperature dependent on neurosensory machinery (daf-10/IFT122, insulin/IGF-1 signaling (daf-16/FOXO, and steroidal signaling (daf-12/FXR. Surprisingly, daf-41 mutation alters the longevity response to temperature, living longer than wild-type at 25°C but shorter than wild-type at 15°C. Longevity phenotypes at 25°C work through daf-16/FOXO and heat shock factor hsf-1, while short lived phenotypes converge on daf-16/FOXO and depend on the daf-12/FXR steroid receptor. Correlatively daf-41 affected expression of DAF-16 and HSF-1 target genes at high temperature, and nuclear extracts from daf-41 animals showed increased occupancy of the heat shock response element. Our studies suggest that daf-41/p23 modulates key transcriptional changes in longevity pathways in response to temperature.

The longevity of broadleaf deciduous trees in Northern Hemisphere temperate forests: insights from tree-ring series

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Alfredo eDi Filippo

2015-05-01

Full Text Available Understanding the factors controlling the expression of longevity in trees is still an outstanding challenge for tree biologists and forest ecologists. We gathered tree-ring data and literature for broadleaf deciduous (BD temperate trees growing in closed-canopy old-growth forests in the Northern Hemisphere to explore the role of geographic patterns, climate variability, and growth rates on longevity. Our pan-continental analysis, covering 32 species from 12 genera, showed that 300-400 years can be considered a baseline threshold for maximum tree lifespan in many temperate deciduous forests. Maximum age varies greatly in relation to environmental features, even within the same species. Tree longevity is generally promoted by reduced growth rates across large genetic differences and environmental gradients. We argue that slower growth rates, and the associated smaller size, provide trees with an advantage against biotic and abiotic disturbance agents, supporting the idea that size, not age, is the main constraint to tree longevity. The oldest trees were living most of their life in subordinate canopy conditions and/or within primary forests in cool temperate environments and outside major storm tracks. Very old trees are thus characterized by slow growth and often live in forests with harsh site conditions and infrequent disturbance events that kill much of the trees. Temperature inversely controls the expression of longevity in mesophilous species (Fagus spp., but its role in Quercus spp. is more complex and warrants further research in disturbance ecology. Biological, ecological and historical drivers must be considered to understand the constraints imposed to longevity within different forest landscapes.

ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion.

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Chen, Wei-Ta; Ebelt, Nancy D; Stracker, Travis H; Xhemalce, Blerta; Van Den Berg, Carla L; Miller, Kyle M

2015-06-01

Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression.

Regulations, policies and practices concerning work stress in five European countries

NARCIS (Netherlands)

Kompier, M.; Gier, E. de; Smulders, P.; Draaisma, D.

1994-01-01

A comparative inventory of regulations, policies and practices in The Netherlands, Sweden, UK, Germany and France with regard to the prevention of work stress was carried out. In each country data were collected by means of interviews with key informants and through exploring relevant documents and

Adrenal Gland Microenvironment and Its Involvement in the Regulation of Stress-induced Hormone Secretion during Sepsis.

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Waldemar Kanczkowski

2016-12-01

Full Text Available Survival of all living organisms depends on maintenance of a steady state of homeostasis, which process relies on its ability to react and adapt to various physical and emotional threats. The defense against stress is executed by the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal medullary system. Adrenal gland is a major effector organ of stress system. During stress adrenal gland rapidly respond with increased secretion of glucocorticoids and catecholamines into circulation, which hormones, in turn, affect metabolism, to provide acutely energy, vasculature to increase blood pressure and the immune system to prevent it from extensive activation. Sepsis resulting from microbial infections is a sustained and extreme example of stress situation. In many critical ill patients levels of both corticotropin-releasing hormone and adrenocorticotropin, two major regulators of adrenal hormone production, are suppressed. Levels of glucocorticoids however, remain normal or are elevated in these patients, suggesting a shift from central to local intraadrenal regulation of adrenal stress response. Among many mechanisms potentially involved in this process, reduced glucocorticoid metabolism and local intraadrenal activation of hormone production mediated by adrenocortical and chromaffin cell interactions, the adrenal vascular system and the immune-adrenal crosstalk play a key role. Consequently, any impairment in function of these systems, can ultimately affect adrenal stress response. The purpose of this mini review is to present and discuss recent advances in our understanding of the adrenal gland microenvironment, and its role in regulation of stress-induced hormone secretion.

The emergence of longevous populations

DEFF Research Database (Denmark)

Colchero, Fernando; Rau, Roland; Jones, Owen R

2016-01-01

The human lifespan has traversed a long evolutionary and historical path, from short-lived primate ancestors to contemporary Japan, Sweden, and other longevity frontrunners. Analyzing this trajectory is crucial for understanding biological and sociocultural processes that determine the span of life....... Here we reveal a fundamental regularity. Two straight lines describe the joint rise of life expectancy and lifespan equality: one for primates and the second one over the full range of human experience from average lifespans as low as 2 y during mortality crises to more than 87 y for Japanese women...... for research on inequality, sociality, and aging....

Explaining Optimistic Old Age Disability and Longevity Expectations

Science.gov (United States)

Costa-Font, Joan; Costa-Font, Montserrat

2011-01-01

Biased health care decision making has been regarded as responsible for inefficient behaviours (for example, the limited insurance purchase). This paper empirically examines two sets of biases in the perception of old age disability and longevity. Particularly, we test for the existence of a so called cumulative bias and, secondly, a so called…

Stress regulated members of the plant organic cation transporter family are localized to the vacuolar membrane

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Koch Wolfgang

2008-07-01

Full Text Available Abstract Background In Arabidopsis six genes group into the gene family of the organic cation transporters (OCTs. In animals the members of the OCT-family are mostly characterized as polyspecific transporters involved in the homeostasis of solutes, the transport of monoamine neurotransmitters and the transport of choline and carnitine. In plants little is known about function, localisation and regulation of this gene family. Only one protein has been characterized as a carnitine transporter at the plasma membrane so far. Findings We localized the five uncharacterized members of the Arabidopsis OCT family, designated OCT2-OCT6, via GFP fusions and protoplast transformation to the tonoplast. Expression analysis with RNA Gel Blots showed a distinct, organ-specific expression pattern of the individual genes. With reporter gene fusion of four members we analyzed the tissue specific distribution of OCT2, 3, 4, and 6. In experiments with salt, drought and cold stress, we could show that AtOCT4, 5 and 6 are up-regulated during drought stress, AtOCT3 and 5 during cold stress and AtOCT 5 and 6 during salt stress treatments. Conclusion Localisation of the proteins at the tonoplast and regulation of the gene expression under stress conditions suggests a specific role for the transporters in plant adaptation to environmental stress.

Effect of gamma irradiation on larval longevity of Chironomus Riparius Meigen. Vol. 4

Energy Technology Data Exchange (ETDEWEB)

Samira, A A [Dept. of Entomology, Univ. of Ain Shams., Cairo (Egypt); El-Halfawy, N [National Centre radiation Research and Technology, Cairo (Egypt); El-Ebiarie, A S [Dept. of Zoology, Fac. of Science, Univ. of Helwan., Cairi (Egypt)

1996-03-01

Whole body irradiation is known to shorten the life-span of insects. This is further investigated in aquatic insect larvae, as part of a programme concerned with stress responses on these larvae. The effect of gamma rays on the longevity of different larval instars of midge Chironomus Riparius was investigated by using five doses of 1, 9, 30, 200 and 1000 Gy of gamma rays. Lt{sub 50} (the time in days required for killing 50% of the population) was estimated using spss{sup x} programme. Data showed that irradiation decreased Lt{sub 50} in the second, third and fourth instars in comparison to their control, while in the first instar, irradiation increased Lt{sub 50} for all doses used. Shortening or increasing life was independent of the dose. Results were explained in terms of possibility of inhibition of enzymes. 1 fig., 1 tab.

WRKY proteins: signaling and regulation of expression during abiotic stress responses.

Science.gov (United States)

Banerjee, Aditya; Roychoudhury, Aryadeep

2015-01-01

WRKY proteins are emerging players in plant signaling and have been thoroughly reported to play important roles in plants under biotic stress like pathogen attack. However, recent advances in this field do reveal the enormous significance of these proteins in eliciting responses induced by abiotic stresses. WRKY proteins act as major transcription factors, either as positive or negative regulators. Specific WRKY factors which help in the expression of a cluster of stress-responsive genes are being targeted and genetically modified to induce improved abiotic stress tolerance in plants. The knowledge regarding the signaling cascade leading to the activation of the WRKY proteins, their interaction with other proteins of the signaling pathway, and the downstream genes activated by them are altogether vital for justified targeting of the WRKY genes. WRKY proteins have also been considered to generate tolerance against multiple abiotic stresses with possible roles in mediating a cross talk between abiotic and biotic stress responses. In this review, we have reckoned the diverse signaling pattern and biological functions of WRKY proteins throughout the plant kingdom along with the growing prospects in this field of research.

Novel Regulation of Aquaporins during Osmotic Stress1

Science.gov (United States)

Vera-Estrella, Rosario; Barkla, Bronwyn J.; Bohnert, Hans J.; Pantoja, Omar

2004-01-01

Aquaporin protein regulation and redistribution in response to osmotic stress was investigated. Ice plant (Mesembryanthemum crystallinum) McTIP1;2 (McMIPF) mediated water flux when expressed in Xenopus leavis oocytes. Mannitol-induced water imbalance resulted in increased protein amounts in tonoplast fractions and a shift in protein distribution to other membrane fractions, suggesting aquaporin relocalization. Indirect immunofluorescence labeling also supports a change in membrane distribution for McTIP1;2 and the appearance of a unique compartment where McTIP1;2 is expressed. Mannitol-induced redistribution of McTIP1;2 was arrested by pretreatment with brefeldin A, wortmannin, and cytochalasin D, inhibitors of vesicle trafficking-related processes. Evidence suggests a role for glycosylation and involvement of a cAMP-dependent signaling pathway in McTIP1;2 redistribution. McTIP1;2 redistribution to endosomal compartments may be part of a homeostatic process to restore and maintain cellular osmolarity under osmotic-stress conditions. PMID:15299122

Emotion regulation's relationships with depression, anxiety and stress due to imagined smartphone and social media loss.

Science.gov (United States)

Elhai, Jon D; Hall, Brian J; Erwin, Meredith Claycomb

2018-03-01

A sample of 359 students participated in a web survey, administered the Emotion Regulation Questionnaire, and Depression Anxiety Stress Scale-21 (DASS-21) as a pre-test. We subsequently randomly assigned subjects to either 1) a smart phone loss group or 2) social media accounts loss group. We asked them to imagine losing two days' access to the technology in their respective group, and rate associated symptoms using the DASS-21. Compared to subjects in the smartphone loss group, social media loss subjects evidenced stronger relations between suppressive emotion regulation with depression, anxiety and stress from imagined loss. Controlling for age and gender, social media loss subjects' increased use of suppression, and decreased use of cognitive reappraisal in emotion regulation, were related to depression, stress and (for suppression only) anxiety due to imagined lost social media. Emotion regulation was not related to psychopathology for subjects in the smartphone loss scenario. Results suggest that emotion dysregulation may be associated with psychopathology from social media loss. Copyright © 2017 Elsevier B.V. All rights reserved.

The Arabidopsis thaliana mutant air1 implicates SOS3 in the regulation of anthocyanins under salt stress

KAUST Repository

Van Oosten, Michael James

2013-08-08

The accumulation of anthocyanins in plants exposed to salt stress has been largely documented. However, the functional link and regulatory components underlying the biosynthesis of these molecules during exposure to stress are largely unknown. In a screen of second site suppressors of the salt overly sensitive3-1 (sos3-1) mutant, we isolated the anthocyanin-impaired-response-1 (air1) mutant. air1 is unable to accumulate anthocyanins under salt stress, a key phenotype of sos3-1 under high NaCl levels (120 mM). The air1 mutant showed a defect in anthocyanin production in response to salt stress but not to other stresses such as high light, low phosphorous, high temperature or drought stress. This specificity indicated that air1 mutation did not affect anthocyanin biosynthesis but rather its regulation in response to salt stress. Analysis of this mutant revealed a T-DNA insertion at the first exon of an Arabidopsis thaliana gene encoding for a basic region-leucine zipper transcription factor. air1 mutants displayed higher survival rates compared to wild-type in oxidative stress conditions, and presented an altered expression of anthocyanin biosynthetic genes such as F3H, F3′H and LDOX in salt stress conditions. The results presented here indicate that AIR1 is involved in the regulation of various steps of the flavonoid and anthocyanin accumulation pathways and is itself regulated by the salt-stress response signalling machinery. The discovery and characterization of AIR1 opens avenues to dissect the connections between abiotic stress and accumulation of antioxidants in the form of flavonoids and anthocyanins. © 2013 Springer Science+Business Media Dordrecht.

Stathmin Mediates Hepatocyte Resistance to Death from Oxidative Stress by down Regulating JNK

Science.gov (United States)

Zhao, Enpeng; Amir, Muhammad; Lin, Yu; Czaja, Mark J.

2014-01-01

Stathmin 1 performs a critical function in cell proliferation by regulating microtubule polymerization. This proliferative function is thought to explain the frequent overexpression of stathmin in human cancer and its correlation with a bad prognosis. Whether stathmin also functions in cell death pathways is unclear. Stathmin regulates microtubules in part by binding free tubulin, a process inhibited by stathmin phosphorylation from kinases including c-Jun N-terminal kinase (JNK). The involvement of JNK activation both in stathmin phosphorylation, and in hepatocellular resistance to oxidative stress, led to an examination of the role of stathmin/JNK crosstalk in oxidant-induced hepatocyte death. Oxidative stress from menadione-generated superoxide induced JNK-dependent stathmin phosphorylation at Ser-16, Ser-25 and Ser-38 in hepatocytes. A stathmin knockdown sensitized hepatocytes to both apoptotic and necrotic cell death from menadione without altering levels of oxidant generation. The absence of stathmin during oxidative stress led to JNK overactivation that was the mechanism of cell death as a concomitant knockdown of JNK1 or JNK2 blocked death. Hepatocyte death from JNK overactivation was mediated by the effects of JNK on mitochondria. Mitochondrial outer membrane permeabilization occurred in stathmin knockdown cells at low concentrations of menadione that triggered apoptosis, whereas mitochondrial β-oxidation and ATP homeostasis were compromised at higher, necrotic menadione concentrations. Stathmin therefore mediates hepatocyte resistance to death from oxidative stress by down regulating JNK and maintaining mitochondrial integrity. These findings demonstrate a new mechanism by which stathmin promotes cell survival and potentially tumor growth. PMID:25285524

Stathmin mediates hepatocyte resistance to death from oxidative stress by down regulating JNK.

Directory of Open Access Journals (Sweden)

Enpeng Zhao

Full Text Available Stathmin 1 performs a critical function in cell proliferation by regulating microtubule polymerization. This proliferative function is thought to explain the frequent overexpression of stathmin in human cancer and its correlation with a bad prognosis. Whether stathmin also functions in cell death pathways is unclear. Stathmin regulates microtubules in part by binding free tubulin, a process inhibited by stathmin phosphorylation from kinases including c-Jun N-terminal kinase (JNK. The involvement of JNK activation both in stathmin phosphorylation, and in hepatocellular resistance to oxidative stress, led to an examination of the role of stathmin/JNK crosstalk in oxidant-induced hepatocyte death. Oxidative stress from menadione-generated superoxide induced JNK-dependent stathmin phosphorylation at Ser-16, Ser-25 and Ser-38 in hepatocytes. A stathmin knockdown sensitized hepatocytes to both apoptotic and necrotic cell death from menadione without altering levels of oxidant generation. The absence of stathmin during oxidative stress led to JNK overactivation that was the mechanism of cell death as a concomitant knockdown of JNK1 or JNK2 blocked death. Hepatocyte death from JNK overactivation was mediated by the effects of JNK on mitochondria. Mitochondrial outer membrane permeabilization occurred in stathmin knockdown cells at low concentrations of menadione that triggered apoptosis, whereas mitochondrial β-oxidation and ATP homeostasis were compromised at higher, necrotic menadione concentrations. Stathmin therefore mediates hepatocyte resistance to death from oxidative stress by down regulating JNK and maintaining mitochondrial integrity. These findings demonstrate a new mechanism by which stathmin promotes cell survival and potentially tumor growth.

Salt stress encourages proline accumulation by regulating proline biosynthesis and degradation in Jerusalem artichoke plantlets.

Science.gov (United States)

Huang, Zengrong; Zhao, Long; Chen, Dandan; Liang, Mingxiang; Liu, Zhaopu; Shao, Hongbo; Long, Xiaohua

2013-01-01

Proline accumulation is an important mechanism for osmotic regulation under salt stress. In this study, we evaluated proline accumulation profiles in roots, stems and leaves of Jerusalem artichoke (Helianthus tuberosus L.) plantlets under NaCl stress. We also examined HtP5CS, HtOAT and HtPDH enzyme activities and gene expression patterns of putative HtP5CS1, HtP5CS2, HtOAT, HtPDH1, and HtPDH2 genes. The objective of our study was to characterize the proline regulation mechanisms of Jerusalem artichoke, a moderately salt tolerant species, under NaCl stress. Jerusalem artichoke plantlets were observed to accumulate proline in roots, stems and leaves during salt stress. HtP5CS enzyme activities were increased under NaCl stress, while HtOAT and HtPDH activities generally repressed. Transcript levels of HtP5CS2 increased while transcript levels of HtOAT, HtPDH1 and HtPDH2 generally decreased in response to NaCl stress. Our results supports that for Jerusalem artichoke, proline synthesis under salt stress is mainly through the Glu pathway, and HtP5CS2 is predominant in this process while HtOAT plays a less important role. Both HtPDH genes may function in proline degradation.

Nutrient Intake Is Associated with Longevity Characterization by Metabolites and Element Profiles of Healthy Centenarians

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Da Cai

2016-09-01

Full Text Available The relationships between diet and metabolites as well as element profiles in healthy centenarians are important but remain inconclusive. Therefore, to test the interesting hypothesis that there would be distinctive features of metabolites and element profiles in healthy centenarians, and that these would be associated with nutrient intake; the short chain fatty acids (SCFAs, total bile acids and ammonia in feces, phenol, p-cresol, uric acid, urea, creatinine and ammonia in urine, and element profiles in fingernails were determined in 90 healthy elderly people, including centenarians from Bama county (China—a famous longevous region—and elderly people aged 80–99 from the longevous region and a non-longevous region. The partial least squares-discriminant analysis was used for pattern recognition. As a result, the centenarians showed a distinct metabolic pattern. Seven characteristic components closely related to the centenarians were identified, including acetic acid, total SCFA, Mn, Co, propionic acid, butyric acid and valeric acid. Their concentrations were significantly higher in the centenarians group (p < 0.05. Additionally, the dietary fiber intake was positively associated with butyric acid contents in feces (r = 0.896, p < 0.01, and negatively associated with phenol in urine (r = −0.326, p < 0.01. The results suggest that the specific metabolic pattern of centenarians may have an important and positive influence on the formation of the longevity phenomenon. Elevated dietary fiber intake should be a path toward health and longevity.

The role of ZmWRKY4 in regulating maize antioxidant defense under cadmium stress

International Nuclear Information System (INIS)

Hong, Changyong; Cheng, Dan; Zhang, Guoqiang; Zhu, Dandan; Chen, Yahua; Tan, Mingpu

2017-01-01

WRKY transcription factors act as positive regulators in abiotic stress responses by activation of the cellular antioxidant systems. However, there are few reports on the response of WRKY genes to cadmium (Cd) stress. In this study, the role of maize ZmWRKY4 in regulating antioxidant enzymes in Cd stress was investigated. The results indicated that Cd induced up-regulation of the expression and the activities of ZmWRKY4 and superoxide dismutase (SOD) and ascorbate peroxidase (APX). Transient expression and RNA interference (RNAi) silencing of ZmWRKY4 in maize mesophyll protoplasts further revealed that ZmWRKY4 was required for the abscisic acid (ABA)-induced increase in expression and activity of SOD and APX. Overexpression of ZmWRKY4 in protoplasts upregulated the expression and the activities of antioxidant enzymes, whereas ABA induced increases in the expression and the activities of antioxidant enzymes were blocked by the RNAi silencing of ZmWRKY4. Bioinformatic analysis indicated that ZmSOD4 and ZmcAPX both harbored two W-boxes, binding motif for WRKY transcription factors, in their promoter region. Intriguingly, ZmWRKY4 belongs to group I WRKYs with two WRKY domains. Moreover, the synchronized expression patterns indicate that ZmWRKY4 might play a critical role in either regulating the ZmSOD4 and ZmcAPX expression or cooperating with them in response to stress and phytohormone. - Highlights: • Cd induced the expression of ZmWRKY4, ZmSOD4 and ZmcAPX. • Maize transcription factor ZmWRKY4 was localized in nucleus. • Overexpression of ZmWRKY4 upregulated the expression of ZmSOD4 and ZmcAPX and the activities of antioxidant enzymes.

A skeletochronological study of growth, longevity, and age at sexual ...

Indian Academy of Sciences (India)

Unknown

nearest mm, body weight, and reproductive status were recorded. Before release ..... analysis to ascertain whether bone resorption might have completely removed one or .... distribution and longevity in the Ramsey Canyon leopard frog, Rana ...

Regulation of Calcium on Peanut Photosynthesis Under Low Night Temperature Stress

Institute of Scientific and Technical Information of China (English)

LIU Yi-fei; HAN Xiao-ri; ZHAN Xiu-mei; YANG Jin-feng; WANG Yu-zhi; SONG Qiao-bo; CHEN Xin

2013-01-01

The effects of different levels of CaCl2 on photosynthesis under low night temperature (8°C) stress in peanuts were studied in order to ifnd out the appropriate concentration of Ca2+ through the artiifcial climate chamber potted culture test. The results indicated that Ca2+, by means of improving the stomatal conductivity of peanut leaves under low night temperature stress, may mitigate the decline of photosynthetic rate in the peanut leaves. The regulation with 15 mmol L-1 CaCl2 (Ca15) was the most effective, compared with other treatments. Subsequently, the improvement of Ca2+ on peanut photosynthesis under low night temperature stress was validated further through spraying withCa15, Ca2+ chelator (ethylene glycol bis(2-aminoethyl) tetraacetic acid; EGTA) and calmodulin antagonists (trilfuonerazine; TFP).And CaM (Ca2+-modulin) played an important role in the nutritional signal transduction for Ca2+ mitigating photosynthesis limitations in peanuts under low night temperature stress.

Salt Stress Represses Soybean Seed Germination by Negatively Regulating GA Biosynthesis While Positively Mediating ABA Biosynthesis.

Science.gov (United States)

Shu, Kai; Qi, Ying; Chen, Feng; Meng, Yongjie; Luo, Xiaofeng; Shuai, Haiwei; Zhou, Wenguan; Ding, Jun; Du, Junbo; Liu, Jiang; Yang, Feng; Wang, Qiang; Liu, Weiguo; Yong, Taiwen; Wang, Xiaochun; Feng, Yuqi; Yang, Wenyu

2017-01-01

Soybean is an important and staple oilseed crop worldwide. Salinity stress has adverse effects on soybean development periods, especially on seed germination and post-germinative growth. Improving seed germination and emergence will have positive effects under salt stress conditions on agricultural production. Here we report that NaCl delays soybean seed germination by negatively regulating gibberellin (GA) while positively mediating abscisic acid (ABA) biogenesis, which leads to a decrease in the GA/ABA ratio. This study suggests that fluridone (FLUN), an ABA biogenesis inhibitor, might be a potential plant growth regulator that can promote soybean seed germination under saline stress. Different soybean cultivars, which possessed distinct genetic backgrounds, showed a similar repressed phenotype during seed germination under exogenous NaCl application. Biochemical analysis revealed that NaCl treatment led to high MDA (malondialdehyde) level during germination and the post-germinative growth stages. Furthermore, catalase, superoxide dismutase, and peroxidase activities also changed after NaCl treatment. Subsequent quantitative Real-Time Polymerase Chain Reaction analysis showed that the transcription levels of ABA and GA biogenesis and signaling genes were altered after NaCl treatment. In line with this, phytohormone measurement also revealed that NaCl considerably down-regulated active GA 1 , GA 3 , and GA 4 levels, whereas the ABA content was up-regulated; and therefore ratios, such as GA 1 /ABA, GA 3 /ABA, and GA 4 /ABA, are decreased. Consistent with the hormonal quantification, FLUN partially rescued the delayed-germination phenotype caused by NaCl-treatment. Altogether, these results demonstrate that NaCl stress inhibits soybean seed germination by decreasing the GA/ABA ratio, and that FLUN might be a potential plant growth regulator that could promote soybean seed germination under salinity stress.

Salt Stress Represses Soybean Seed Germination by Negatively Regulating GA Biosynthesis While Positively Mediating ABA Biosynthesis

Directory of Open Access Journals (Sweden)

Kai Shu

2017-08-01

Full Text Available Soybean is an important and staple oilseed crop worldwide. Salinity stress has adverse effects on soybean development periods, especially on seed germination and post-germinative growth. Improving seed germination and emergence will have positive effects under salt stress conditions on agricultural production. Here we report that NaCl delays soybean seed germination by negatively regulating gibberellin (GA while positively mediating abscisic acid (ABA biogenesis, which leads to a decrease in the GA/ABA ratio. This study suggests that fluridone (FLUN, an ABA biogenesis inhibitor, might be a potential plant growth regulator that can promote soybean seed germination under saline stress. Different soybean cultivars, which possessed distinct genetic backgrounds, showed a similar repressed phenotype during seed germination under exogenous NaCl application. Biochemical analysis revealed that NaCl treatment led to high MDA (malondialdehyde level during germination and the post-germinative growth stages. Furthermore, catalase, superoxide dismutase, and peroxidase activities also changed after NaCl treatment. Subsequent quantitative Real-Time Polymerase Chain Reaction analysis showed that the transcription levels of ABA and GA biogenesis and signaling genes were altered after NaCl treatment. In line with this, phytohormone measurement also revealed that NaCl considerably down-regulated active GA1, GA3, and GA4 levels, whereas the ABA content was up-regulated; and therefore ratios, such as GA1/ABA, GA3/ABA, and GA4/ABA, are decreased. Consistent with the hormonal quantification, FLUN partially rescued the delayed-germination phenotype caused by NaCl-treatment. Altogether, these results demonstrate that NaCl stress inhibits soybean seed germination by decreasing the GA/ABA ratio, and that FLUN might be a potential plant growth regulator that could promote soybean seed germination under salinity stress.

Liability-driven investment in longevity risk management

OpenAIRE

Helena Aro; Teemu Pennanen

2013-01-01

This paper studies optimal investment from the point of view of an investor with longevity-linked liabilities. The relevant optimization problems rarely are analytically tractable, but we are able to show numerically that liability driven investment can significantly outperform common strategies that do not take the liabilities into account. In problems without liabilities the advantage disappears, which suggests that the superiority of the proposed strategies is indeed based on connections b...

Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan.

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Erhan Bilal

Full Text Available We report results from the analysis of complete mitochondrial DNA (mtDNA sequences from 112 Japanese semi-supercentenarians (aged above 105 years combined with previously published data from 96 patients in each of three non-disease phenotypes: centenarians (99-105 years of age, healthy non-obese males, obese young males and four disease phenotypes, diabetics with and without angiopathy, and Alzheimer's and Parkinson's disease patients. We analyze the correlation between mitochondrial polymorphisms and the longevity phenotype using two different methods. We first use an exhaustive algorithm to identify all maximal patterns of polymorphisms shared by at least five individuals and define a significance score for enrichment of the patterns in each phenotype relative to healthy normals. Our study confirms the correlations observed in a previous study showing enrichment of a hierarchy of haplogroups in the D clade for longevity. For the extreme longevity phenotype we see a single statistically significant signal: a progressive enrichment of certain "beneficial" patterns in centenarians and semi-supercentenarians in the D4a haplogroup. We then use Principal Component Spectral Analysis of the SNP-SNP Covariance Matrix to compare the measured eigenvalues to a Null distribution of eigenvalues on Gaussian datasets to determine whether the correlations in the data (due to longevity arises from some property of the mutations themselves or whether they are due to population structure. The conclusion is that the correlations are entirely due to population structure (phylogenetic tree. We find no signal for a functional mtDNA SNP correlated with longevity. The fact that the correlations are from the population structure suggests that hitch-hiking on autosomal events is a possible explanation for the observed correlations.

Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism.

Science.gov (United States)

Jansen, S W; Akintola, A A; Roelfsema, F; van der Spoel, E; Cobbaert, C M; Ballieux, B E; Egri, P; Kvarta-Papp, Z; Gereben, B; Fekete, C; Slagboom, P E; van der Grond, J; Demeneix, B A; Pijl, H; Westendorp, R G J; van Heemst, D

2015-06-19

Few studies have included subjects with the propensity to reach old age in good health, with the aim to disentangle mechanisms contributing to staying healthier for longer. The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating levels of thyroid stimulating hormone (TSH) and thyroid hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis may favour longevity without altering energy metabolism.

Three dimensions of the survival curve: horizontalization, verticalization, and longevity extension.

Science.gov (United States)

Cheung, Siu Lan Karen; Robine, Jean-Marie; Tu, Edward Jow-Ching; Caselli, Graziella

2005-05-01

Three dimensions of the survival curve have been developed: (1) "horizontalization," which corresponds to how long a cohort and how many survivors can live before aging-related deaths significantly decrease the proportion of survivors; (2) "verticalization," which corresponds to how concentrated aging-related ("normal") deaths are around the modal age at death (M); and (3) "longevity extension," which corresponds to how far the highest normal life durations can exceed M. Our study shows that the degree of horizontalization increased relatively less than the degree of verticalization in Hong Kong from 1976 to 2001. After age normalization, the highest normal life durations moved closer to M, implying that the increase in human longevity is meeting some resistance.

P-body proteins regulate transcriptional rewiring to promote DNA replication stress resistance.

Science.gov (United States)

Loll-Krippleber, Raphael; Brown, Grant W

2017-09-15

mRNA-processing (P-) bodies are cytoplasmic granules that form in eukaryotic cells in response to numerous stresses to serve as sites of degradation and storage of mRNAs. Functional P-bodies are critical for the DNA replication stress response in yeast, yet the repertoire of P-body targets and the mechanisms by which P-bodies promote replication stress resistance are unknown. In this study we identify the complete complement of mRNA targets of P-bodies during replication stress induced by hydroxyurea treatment. The key P-body protein Lsm1 controls the abundance of HHT1, ACF4, ARL3, TMA16, RRS1 and YOX1 mRNAs to prevent their toxic accumulation during replication stress. Accumulation of YOX1 mRNA causes aberrant downregulation of a network of genes critical for DNA replication stress resistance and leads to toxic acetaldehyde accumulation. Our data reveal the scope and the targets of regulation by P-body proteins during the DNA replication stress response.P-bodies form in response to stress and act as sites of mRNA storage and degradation. Here the authors identify the mRNA targets of P-bodies during DNA replication stress, and show that P-body proteins act to prevent toxic accumulation of these target transcripts.

Up-regulation of Kir2.1 by ER stress facilitates cell death of brain capillary endothelial cells

International Nuclear Information System (INIS)

Kito, Hiroaki; Yamazaki, Daiju; Ohya, Susumu; Yamamura, Hisao; Asai, Kiyofumi; Imaizumi, Yuji

2011-01-01

Highlights: → We found that application of endoplasmic reticulum (ER) stress with tunicamycin to brain capillary endothelial cells (BCECs) induced cell death. → The ER stress facilitated the expression of inward rectifier K + channel (K ir 2.1) and induced sustained membrane hyperpolarization. → The membrane hyperpolarization induced sustained Ca 2+ entry through voltage-independent nonspecific cation channels and consequently facilitated cell death. → The K ir 2.1 up-regulation by ER stress is, at least in part, responsible for cell death of BCECs under pathological conditions. -- Abstract: Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to maintain brain homeostasis. Cell turnover of BCECs by the balance of cell proliferation and cell death is critical for maintaining the integrity of BBB. Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress inducer, up-regulated inward rectifier K + channel (K ir 2.1) and facilitated cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of K ir channels contributed to the establishment of deeply negative resting membrane potential in t-BBEC117. The deep resting membrane potential increased the resting intracellular Ca 2+ concentration due to Ca 2+ influx through non-selective cation channels and thereby partly but significantly regulated cell death in t-BBEC117. The present results suggest that the up-regulation of K ir 2.1 is, at least in part, responsible for cell death/cell turnover of BCECs induced by a variety of cellular stresses, particularly ER stress, under pathological conditions.