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Sample records for regimens extend lifespan

  1. Nutritional regimens with periodically recurring phases of dietary restriction extend lifespan in Drosophila.

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    Romey-Glüsing, Renja; Li, Yang; Hoffmann, Julia; von Frieling, Jakob; Knop, Mirjam; Pfefferkorn, Roxana; Bruchhaus, Iris; Fink, Christine; Roeder, Thomas

    2018-04-01

    Nutritional interventions such as caloric and dietary restriction increase lifespan in various animal models. To identify alternative and less demanding nutritional interventions that extend lifespan, we subjected fruit flies ( Drosophila melanogaster) to weekly nutritional regimens that involved alternating a conventional diet with dietary restriction. Short periods of dietary restriction (up to 2 d) followed by longer periods of a conventional diet yielded minimal increases in lifespan. We found that 3 or more days of contiguous dietary restriction (DR) was necessary to yield a lifespan extension similar to that observed with persistent DR. Female flies were more responsive to these interventions than males. Physiologic changes known to be associated with prolonged DR, such as reduced metabolic rates, showed the same time course as lifespan extension. Moreover, concurrent transcriptional changes indicative of reduced insulin signaling were identified with DR. These physiologic and transcriptional changes were sustained, as they were detectable several days after switching to conventional diets. Taken together, diets with longer periods of DR extended lifespan concurrently with physiologic and transcriptional changes that may underlie this increase in lifespan.-Romey-Glüsing, R., Li, Y., Hoffmann, J., von Frieling, J., Knop, M., Pfefferkorn, R., Bruchhaus, I., Fink, C., Roeder, T. Nutritional regimens with periodically recurring phases of dietary restriction extend lifespan in Drosophila.

  2. Nicotinamide extends replicative lifespan of human cells.

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    Kang, Hyun Tae; Lee, Hyung Il; Hwang, Eun Seong

    2006-10-01

    We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production.

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

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    Dror Sagi

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

  4. Lower Doses of Fructose Extend Lifespan in Caenorhabditis elegans.

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    Zheng, Jolene; Gao, Chenfei; Wang, Mingming; Tran, Phuongmai; Mai, Nancy; Finley, John W; Heymsfield, Steven B; Greenway, Frank L; Li, Zhaoping; Heber, David; Burton, Jeffrey H; Johnson, William D; Laine, Roger A

    2017-05-04

    Epidemiological studies indicate that the increased consumption of sugars including sucrose and fructose in beverages correlate with the prevalence of obesity, type-2 diabetes, insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension in humans. A few reports suggest that fructose extends lifespan in Saccharomyces cerevisiae. In Anopheles gambiae, fructose, glucose, or glucose plus fructose also extended lifespan. New results presented here suggest that fructose extends lifespan in Caenorhabditis elegans (C. elegans) wild type (N2). C. elegans were fed standard laboratory food source (E. coli OP50), maintained in liquid culture. Experimental groups received additional glucose (111 mM), fructose (55 mM, 111 mM, or 555 mM), sucrose (55 mM, 111 mM, or 555 mM), glucose (167 mM) plus fructose (167 mM) (G&F), or high fructose corn syrup (HFCS, 333 mM). In four replicate experiments, fructose dose-dependently increased mean lifespan at 55 mM or 111 m Min N2, but decreased lifespan at 555 mM (P Glucose reduced lifespan (P fructose (555 mM), glucose (111 mM), and sucrose (55 mM, 111 mM, and 555 mM). Here we report a biphasic effect of fructose increasing lifespan at lower doses and shortening lifespan at higher doses with an inverse effect on IFD. In view of reports that fructose increases lifespan in yeast, mosquitoes and now nematodes, while decreasing fat deposition (in nematodes) at lower concentrations, further research into the relationship of fructose to lifespan and fat accumulation in vertebrates and mammals is indicated.

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

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

    2013-01-01

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

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

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    Mayumi Hachinohe

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

  7. Malate and fumarate extend lifespan in Caenorhabditis elegans.

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    Clare B Edwards

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

  8. Piceatannol extends the lifespan of Caenorhabditis elegans via DAF-16.

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    Shen, Peiyi; Yue, Yiren; Sun, Quancai; Kasireddy, Nandita; Kim, Kee-Hong; Park, Yeonhwa

    2017-05-06

    Piceatannol is a natural stilbene with many beneficial effects, such as antioxidative, anti-inflammatory, antiatherogenic activities; however, its role on aging is not known. In this study, we used Caenorhabditis elegans as an animal model to study the effect of piceatannol on its lifespan and investigated the underlying mechanisms. The results showed that 50 and 100 µM piceatannol significantly extended the lifespan of C. elegans without altering the growth rate, worm size and progeny production. Piceatannol delayed the age-related decline of pumping rate and locomotive activity, and protected the worms from heat and oxidative stress. This study further indicated that lifespan extension and enhanced stress resistance induced by piceatannol requires DAF-16. Since DAF-16 is conserved from nematodes to mammals, our study may have important implications in utilizing piceatannol to promote healthy aging and combat age-related disease in humans. © 2016 BioFactors, 43(3):379-387, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  9. Gengnianchun Extends the Lifespan of Caenorhabditis elegans via the Insulin/IGF-1 Signalling Pathway

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    Fanhui Meng

    2018-01-01

    Full Text Available Gengnianchun (GNC, a traditional Chinese medicine (TCM, is believed to have beneficial effects on ageing-related diseases, such as antioxidant properties and effects against Aβ-induced toxicity. We previously found that GNC extended the lifespan of Caenorhabditis elegans. However, the mechanism underlying this effect was unclear. In this study, we further explored the mechanisms of GNC using a C. elegans model. GNC significantly increased the lifespan of C. elegans and enhanced oxidative and thermal stress resistance. Moreover, chemotaxis increased after GNC treatment. RNA-seq analysis showed that GNC regulated genes associated with longevity. We also conducted lifespan assays with a series of worm mutants. The results showed that GNC significantly extended the lifespan of several mutant strains, including eat-2 (ad465, rsks-1 (ok1255, and glp-1 (e2144, suggesting that the prolongevity effect of GNC is independent of the function of these genes. However, GNC failed to extend the lifespan of daf-2 (e1370, age-1 (hx546, and daf-16 (mu86 mutant strains. Our findings suggest that GNC extends the lifespan of C. elegans via the insulin/IGF-1 signalling pathway and may be a potential antiageing agent.

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

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    Devon eChandler-Brown

    2015-10-01

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

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

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

    2014-04-01

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

  12. Extended regimen combined oral contraception: A review of evolving concepts and acceptance by women and clinicians.

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    Nappi, Rossella E; Kaunitz, Andrew M; Bitzer, Johannes

    2016-01-01

    The clinical utility of extended regimen combined oral contraceptives (COCs) is increasingly being recognised. Our objective was to understand the attitudes of women and clinicians about the use of these regimens. We present the rationale for extended regimen COCs from a historical perspective, and trace their evolution and growing popularity in light of their clinical benefits. We conclude by offering potential strategies for counselling women about extended regimen COC options. We conducted a MEDLINE search to identify and summarise studies of extended regimen COCs, focusing on attitudes of women and clinicians regarding efficacy, safety/tolerability and fewer scheduled bleeding episodes and other potential benefits. The body of contemporary literature on extended regimen COCs suggests that their contraceptive efficacy is comparable to that of conventional 28-day (i.e., 21/7) regimens. For women seeking contraception that allows infrequent scheduled bleeding episodes, particularly those who suffer from hormone withdrawal symptoms and cyclical symptoms (e.g., headache, mood changes, dysmenorrhoea, heavy menstrual bleeding), extended regimen COCs are an effective and safe option. Although satisfaction with extended regimen COCs in clinical trials is high, misperceptions about continuous hormone use may still limit the widespread acceptance of this approach. Despite the widespread acceptance among clinicians of extended regimen COCs as an effective and safe contraceptive option, these regimens are underused, likely due to a lack of awareness about their availability and utility among women. Improved patient education and counselling regarding the safety and benefits of extended regimen COCs may help women make more informed contraceptive choices.

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

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    Yu, Suyeun; Jang, Yeogil; Paik, Donggi; Lee, Eunil; Park, Joong-Jean

    2015-01-01

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

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

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

    2015-10-02

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

  15. Calorie restriction extends the chronological lifespan of Saccharomyces cerevisiae independently of the Sirtuins.

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    Smith, Daniel L; McClure, Julie M; Matecic, Mirela; Smith, Jeffrey S

    2007-10-01

    Calorie restriction (CR) extends the mean and maximum lifespan of a wide variety of organisms ranging from yeast to mammals, although the molecular mechanisms of action remain unclear. For the budding yeast Saccharomyces cerevisiae reducing glucose in the growth medium extends both the replicative and chronological lifespans (CLS). The conserved NAD(+)-dependent histone deacetylase, Sir2p, promotes replicative longevity in S. cerevisiae by suppressing recombination within the ribosomal DNA locus and has been proposed to mediate the effects of CR on aging. In this study, we investigated the functional relationships of the yeast Sirtuins (Sir2p, Hst1p, Hst2p, Hst3p and Hst4p) with CLS and CR. SIR2, HST2, and HST4 were not major regulators of CLS and were not required for the lifespan extension caused by shifting the glucose concentration from 2 to 0.5% (CR). Deleting HST1 or HST3 moderately shortened CLS, but did not prevent CR from extending lifespan. CR therefore works through a Sirtuin-independent mechanism in the chronological aging system. We also show that low temperature or high osmolarity additively extends CLS when combined with CR, suggesting that these stresses and CR act through separate pathways. The CR effect on CLS was not specific to glucose. Restricting other simple sugars such as galactose or fructose also extended lifespan. Importantly, growth on nonfermentable carbon sources that force yeast to exclusively utilize respiration extended lifespan at nonrestricted concentrations and provided no additional benefit when restricted, suggesting that elevated respiration capacity is an important determinant of chronological longevity.

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

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

    2015-12-01

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

  17. Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria.

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    Qian, Minxian; Liu, Zuojun; Peng, Linyuan; Tang, Xiaolong; Meng, Fanbiao; Ao, Ying; Zhou, Mingyan; Wang, Ming; Cao, Xinyue; Qin, Baoming; Wang, Zimei; Zhou, Zhongjun; Wang, Guangming; Gao, Zhengliang; Xu, Jun; Liu, Baohua

    2018-05-02

    DNA damage accumulates with age (Lombard et al., 2005). However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that ATM-centered DNA damage response (DDR) progressively declines with senescence and age, while low dose of chloroquine (CQ) activates ATM, promotes DNA damage clearance, rescues age-related metabolic shift, and prolongs replicative lifespan. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies of Sirt6 extend lifespan in Atm-/- mice, with restored metabolic homeostasis. Moreover, the treatment with CQ remarkably extends lifespan of Caenorhabditis elegans , but not the ATM-1 mutants. In a progeria mouse model with low DNA repair capacity, long-term administration of CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases. © 2018, Qian et al.

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

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    Yoko Honda

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

  19. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

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    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  20. Sulfur restriction extends fission yeast chronological lifespan through Ecl1 family genes by downregulation of ribosome.

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    Ohtsuka, Hokuto; Takinami, Masahiro; Shimasaki, Takafumi; Hibi, Takahide; Murakami, Hiroshi; Aiba, Hirofumi

    2017-07-01

    Nutritional restrictions such as calorie restrictions are known to increase the lifespan of various organisms. Here, we found that a restriction of sulfur extended the chronological lifespan (CLS) of the fission yeast Schizosaccharomyces pombe. The restriction decreased cellular size, RNA content, and ribosomal proteins and increased sporulation rate. These responses depended on Ecl1 family genes, the overexpression of which results in the extension of CLS. We also showed that the Zip1 transcription factor results in the sulfur restriction-dependent expression of the ecl1 + gene. We demonstrated that a decrease in ribosomal activity results in the extension of CLS. Based on these observations, we propose that sulfur restriction extends CLS through Ecl1 family genes in a ribosomal activity-dependent manner. © 2017 John Wiley & Sons Ltd.

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

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

    2009-01-01

    Background Sex differences in lifespan are ubiquitous throughout the animal kingdom but the causes underlying this phenomenon remain poorly understood. Several explanations based on asymmetrical inheritance patterns (sex chromosomes or mitochondrial DNA) have been proposed, but these ideas have...

  2. Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan

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    Nicole M. Templeman

    2017-07-01

    Full Text Available The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1 signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/− mice to Ins2+/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/− mice. Halving Ins2 lowered circulating insulin by 25%–34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan.

  3. Tenebrio molitor Extracts Modulate the Response to Environmental Stressors and Extend Lifespan in Caenorhabditis elegans.

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    Won, Seong-Min; Cha, Hye-Uk; Yi, Sun Shin; Kim, Sung-Jo; Park, Sang-Kyu

    2016-09-08

    Tenebrio molitor are large insects and their larvae are consumed as food in many countries. The nutritional composition of T. molitor has been studied and contains high amounts of proteins, unsaturated fatty acids, and valuable minerals. However, the bioactivity of T. molitor has not been fully understood. We examined the effects of T. molitor extracts on resistance to oxidative stress and organism's lifespan using Caenorhabditis elegans as a model system. The response to heat shock and ultraviolet (UV) irradiation was monitored in vivo. The extracts from T. molitor showed significant effects on resistance to oxidative stress and UV irradiation and extend both mean and maximum lifespan of C. elegans. The number of progeny produced significantly increased in animals supplemented with T. molitor extracts. In addition, the expression of hsp-16.2 and sod-3 was markedly upregulated by supplementation with T. molitor extracts. These findings suggest that T. molitor extracts can increase response to stressors and extend lifespan by the induction of longevity assurance genes in C. elegans.

  4. The normative dimensions of extending the human lifespan by age-related biomedical innovations.

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    Ehni, Hans-Joerg; Marckmann, Georg

    2008-10-01

    The current normative debate on age-related biomedical innovations and the extension of the human lifespan has important shortcomings. Mainly, the complexity of the different normative dimensions relevant for ethical and/or juridicial norms is not fully developed and the normative quality of teleological and deontological arguments is not properly distinguished. This article addresses some of these shortcomings and develops the outline of a more comprehensive normative framework covering all relevant dimensions. Such a frame necessarily has to include conceptions of a good life on the individual and societal levels. Furthermore, as a third dimension, a model for the access to and the just distribution of age-related biomedical innovations and technologies extending the human lifespan will be developed. It is argued that such a model has to include the different levels of the general philosophical theories of distributive justice, including social rights and theories of just health care. Furthermore, it has to show how these theories can be applied to the problem area of aging and extending the human lifespan.

  5. Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.

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    Templeman, Nicole M; Flibotte, Stephane; Chik, Jenny H L; Sinha, Sunita; Lim, Gareth E; Foster, Leonard J; Nislow, Corey; Johnson, James D

    2017-07-11

    The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2 +/- mice to Ins2 +/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2 +/- mice. Halving Ins2 lowered circulating insulin by 25%-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. The Yang-Tonifying Herbal Medicine Cynomorium songaricum Extends Lifespan and Delays Aging in Drosophila

    Directory of Open Access Journals (Sweden)

    Hsin-Ping Liu

    2012-01-01

    Full Text Available Aging is highly correlated with the progressive loss of physiological function, including cognitive behavior and reproductive capacity, as well as an increased susceptibility to diseases; therefore, slowing age-related degeneration could greatly contribute to human health. Cynomorium songaricum Rupr. (CS is traditionally used to improve sexual function and treat kidney dysfunction in traditional Chinese medicine, although little is known about whether CS has effects on longevity. Here, we show that CS supplementation in the diet extends both the mean and maximum lifespan of adult female flies. The increase in lifespan with CS was correlated with higher resistance to oxidative stress and starvation and lower lipid hydroperoxides (LPO levels. Additionally, the lifespan extension was accompanied by beneficial effects, such as improved mating readiness, increased fecundity, and suppression of age-related learning impairment in aged flies. These findings demonstrate the important antiaging effects of CS and indicate the potential applicability of dietary intervention with CS to enhance health and prevent multiple age-related diseases.

  7. Target of rapamycin signalling mediates the lifespan-extending effects of dietary restriction by essential amino acid alteration

    NARCIS (Netherlands)

    Emran, S.; Yang, M.Y.; He, X.L.; Zandveld, J.; Piper, M.D.W.

    2014-01-01

    Dietary restriction (DR), defined as a moderate reduction in food intake short of malnutrition, has been shown to extend healthy lifespan in a diverse range of organisms, from yeast to primates. Reduced signalling through the insulin/IGF-like (IIS) and Target of Rapamycin (TOR) signalling pathways

  8. 10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling

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    Yoko Honda

    2015-01-01

    Full Text Available Royal jelly (RJ produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA, the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA further extended the lifespan of the daf-2 mutants, which exhibit long lifespan through reducing insulin-like signaling (ILS, indicating that 10-HDA extended lifespan independently of ILS. On the other hand, 10-HDA did not extend the lifespan of the eat-2 mutants, which show long lifespan through dietary restriction caused by a food-intake defect. This finding indicates that 10-HDA extends lifespan through dietary restriction signaling. We further found that 10-HDA did not extend the lifespan of the long-lived mutants in daf-15, which encodes Raptor, a target of rapamycin (TOR components, indicating that 10-HDA shared some longevity control mechanisms with TOR signaling. Additionally, 10-HDA was found to confer tolerance against thermal and oxidative stress. 10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling in C. elegans.

  9. 10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling.

    Science.gov (United States)

    Honda, Yoko; Araki, Yoko; Hata, Taketoshi; Ichihara, Kenji; Ito, Masafumi; Tanaka, Masashi; Honda, Shuji

    2015-01-01

    Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA further extended the lifespan of the daf-2 mutants, which exhibit long lifespan through reducing insulin-like signaling (ILS), indicating that 10-HDA extended lifespan independently of ILS. On the other hand, 10-HDA did not extend the lifespan of the eat-2 mutants, which show long lifespan through dietary restriction caused by a food-intake defect. This finding indicates that 10-HDA extends lifespan through dietary restriction signaling. We further found that 10-HDA did not extend the lifespan of the long-lived mutants in daf-15, which encodes Raptor, a target of rapamycin (TOR) components, indicating that 10-HDA shared some longevity control mechanisms with TOR signaling. Additionally, 10-HDA was found to confer tolerance against thermal and oxidative stress. 10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling in C. elegans.

  10. DhHP-6 extends lifespan of Caenorhabditis elegans by enhancing nuclear translocation and transcriptional activity of DAF-16.

    Science.gov (United States)

    Huang, Lei; Li, Pengfei; Wang, Guan; Guan, Shuwen; Sun, Xiaoli; Wang, Liping

    2013-04-01

    Earlier studies have demonstrated that Deuterohaemin-AlaHisThrValGluLys (DhHP-6), a novel porphyrin-peptide, increases lifespan and enhances stress resistance of Caenorhabditis elegans. To explore the possible mechanisms, in this study we investigated the roles of SIR-2.1 and DAF-16 in DhHP-6's function using wild-type and various other mutant strains of C. elegans. DhHP-6's effect was dependent upon DAF-16, and it did not extend the lifespan of the loss-of-function daf-16 mutant strain (daf-16(mu86) I). DhHP-6 enhanced DAF-16 translocation from cytoplasm to nuclei; and it increased DAF-16's transcriptional activity, likely by activating the SIR-2.1/DAF-16 complex. DhHP-6's effect was also dependent upon SIR-2.1, and it did not increase the lifespan of the worms with SIR-2.1 deacetylase activity inhibited by niacin amide (SIR-2.1 inhibitor) and SIR-2.1 RNA interference (RNAi). Niacin amide and RNAi increased DAF-16's nuclear localization; but they decreased DAF-16's transcriptional activity, likely by preventing the formation of the SIR-2.1/DAF-16 complex. These results suggest that DhHP-6 extends the lifespan of C. elegans via SIR 2.1 and DAF-16, and they provide new insights into the molecular mechanisms of aging.

  11. The interplay between protein L-isoaspartyl methyltransferase activity and insulin-like signaling to extend lifespan in Caenorhabditis elegans.

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    Shilpi Khare

    Full Text Available The protein L-isoaspartyl-O-methyltransferase functions to initiate the repair of isomerized aspartyl and asparaginyl residues that spontaneously accumulate with age in a variety of organisms. Caenorhabditis elegans nematodes lacking the pcm-1 gene encoding this enzyme display a normal lifespan and phenotype under standard laboratory growth conditions. However, significant defects in development, egg laying, dauer survival, and autophagy have been observed in pcm-1 mutant nematodes when deprived of food and when exposed to oxidative stress. Interestingly, overexpression of this repair enzyme in both Drosophila and C. elegans extends adult lifespan under thermal stress. In this work, we show the involvement of the insulin/insulin-like growth factor-1 signaling (IIS pathway in PCM-1-dependent lifespan extension in C. elegans. We demonstrate that reducing the levels of the DAF-16 downstream transcriptional effector of the IIS pathway by RNA interference reduces the lifespan extension resulting from PCM-1 overexpression. Using quantitative real-time PCR analysis, we show the up-regulation of DAF-16-dependent stress response genes in the PCM-1 overexpressor animals compared to wild-type and pcm-1 mutant nematodes under mild thermal stress conditions. Additionally, similar to other long-lived C. elegans mutants in the IIS pathway, including daf-2 and age-1 mutants, PCM-1 overexpressor adult animals display increased resistance to severe thermal stress, whereas pcm-1 mutant animals survive less long under these conditions. Although we observe a higher accumulation of damaged proteins in pcm-1 mutant nematodes, the basal level of isoaspartyl residues detected in wild-type animals was not reduced by PCM-1 overexpression. Our results support a signaling role for the protein L-isoaspartyl methyltransferase in lifespan extension that involves the IIS pathway, but that may be independent of its function in overall protein repair.

  12. Extended high dose letrozole regimen versus short low dose letrozole regimen as an adjuvant to gonadotropin releasing hormone antagonist protocol in poor responders undergoing IVF-ET.

    Science.gov (United States)

    Fouda, Usama M; Sayed, Ahmed M

    2011-12-01

    To compare the efficacy and cost-effectiveness of extended high dose letrozole regimen/HPuFSH-gonadotropin releasing hormone antagonist (GnRHant) protocol with short low dose letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET. In this randomized controlled trial, 136 women who responded poorly to GnRH agonist long protocol in their first IVF cycle were randomized into two equal groups using computer generated list and were treated in the second IVF cycle by either extended letrozole regimen (5 mg/day during the first 5 days of cycle and 2.5 mg/day during the subsequent 3 days) combined with HPuFSH-GnRHant protocol or short letrozole regimen (2.5 mg/day from cycle day 3-7) combined with HPuFSH-GnRHant protocol. There were no significant differences between both groups with regard to number of oocytes retrieved and clinical pregnancy rate (5.39 ± 2.08 vs. 5.20 ± 1.88 and 22.06% vs. 16.18%, respectively).The total gonadotropins dose and medications cost per cycle were significantly lower in extended letrozole group (44.87 ± 9.16 vs. 59.97 ± 14.91 ampoules and 616.52 ± 94.97 vs. 746.84 ± 149.21 US Dollars ($), respectively).The cost-effectiveness ratio was 2794 $ in extended letrozole group and 4616 $ in short letrozole group. Extended letrozole regimen/HPuFSH-GnRHant protocol was more cost-effective than short letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET.

  13. The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan.

    Science.gov (United States)

    Mittal, Nitish; Guimaraes, Joao C; Gross, Thomas; Schmidt, Alexander; Vina-Vilaseca, Arnau; Nedialkova, Danny D; Aeschimann, Florian; Leidel, Sebastian A; Spang, Anne; Zavolan, Mihaela

    2017-09-06

    In Saccharomyces cerevisiae, deletion of large ribosomal subunit protein-encoding genes increases the replicative lifespan in a Gcn4-dependent manner. However, how Gcn4, a key transcriptional activator of amino acid biosynthesis genes, increases lifespan, is unknown. Here we show that Gcn4 acts as a repressor of protein synthesis. By analyzing the messenger RNA and protein abundance, ribosome occupancy and protein synthesis rate in various yeast strains, we demonstrate that Gcn4 is sufficient to reduce protein synthesis and increase yeast lifespan. Chromatin immunoprecipitation reveals Gcn4 binding not only at genes that are activated, but also at genes, some encoding ribosomal proteins, that are repressed upon Gcn4 overexpression. The promoters of repressed genes contain Rap1 binding motifs. Our data suggest that Gcn4 is a central regulator of protein synthesis under multiple perturbations, including ribosomal protein gene deletions, calorie restriction, and rapamycin treatment, and provide an explanation for its role in longevity and stress response.The transcription factor Gcn4 is known to regulate yeast amino acid synthesis. Here, the authors show that Gcn4 also acts as a repressor of protein biosynthesis in a range of conditions that enhance yeast lifespan, such as ribosomal protein knockout, calorie restriction or mTOR inhibition.

  14. Active Hexose Correlated Compound Extends the Lifespan and Increases the Thermotolerance of Nematodes

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    Tetsuya Okuyama

    2013-06-01

    Full Text Available ABSTRACTBackground: Active hexose correlated compound (AHCC is the extract from cultured mycelia of Lentinula edodes, a species of Basidiomycetes mushroom. AHCC contains various polysaccharides, including partially acylated -1,4-glucan, which is one of its major constituents. The application of AHCC has been markedly increased in complementary and alternative medicine as a functional food because AHCC improved the prognosis of postoperative hepatocellular carcinoma patients. AHCC has anti-inflammatory and antioxidant effects, such as the suppression of nitric oxide production in hepatocytes. AHCC might affect resistance to environmental stress, which is assumed to play a pivotal role in the longevity of many organisms.Objective: To investigate the effect of AHCC on longevity, we measured the lifespan of the nematode Caenorhabditis elegans, a model animal that is widely used to assess longevity. We also examined the effect of AHCC on resistance to heat stress, i.e., thermotolerance.Methods: The lifespan of C. elegans animals grown on media in the absence or presence of AHCC at 20°C was evaluated. Thermotolerance assays were performed at 35°C, the restrictive temperature of the animals. The effects of AHCC on lifespan and thermotolerance were analyzed with longevity mutants. Expression levels of stress-related genes, including heat shock genes, were measured by strand-specific reverse transcription-polymerase chain reaction after heat shock.Results: Wild-type C. elegans animals exhibited a longer mean lifespan by up to 10% in the presence of AHCC in the growth media than animals in the absence of AHCC. Furthermore, AHCC markedly increased thermotolerance at 35°C. Epistasis analyses showed that lifespan extension by AHCC at least partly required two longevity-promoting transcription factors: DAF-16 (C. elegans homolog of FOXO and HSF-1 (C. elegans homolog of heat shock transcription factor 1. After heat shock, AHCC activated the transcription

  15. Natto (fermented soybean) extract extends the adult lifespan of Caenorhabditis elegans.

    Science.gov (United States)

    Ibe, Sachie; Kumada, Kaoru; Yoshida, Keiko; Otobe, Kazunori

    2013-01-01

    We investigated the effects of a water extract of natto on the aging of the nematode Caenorhabditis elegans. The water extract significantly prolonged the adult lifespan of the wild-type worms and rendered them resistant to oxidative and thermal stress. In addition, treatment with natto extract significantly delayed the accumulation of lipofuscin, a characteristic of aging cells. Our findings suggest that components of natto have a beneficial anti-aging effect in vivo.

  16. Conditional abrogation of Atm in osteoclasts extends osteoclast lifespan and results in reduced bone mass.

    Science.gov (United States)

    Hirozane, Toru; Tohmonda, Takahide; Yoda, Masaki; Shimoda, Masayuki; Kanai, Yae; Matsumoto, Morio; Morioka, Hideo; Nakamura, Masaya; Horiuchi, Keisuke

    2016-09-28

    Ataxia-telangiectasia mutated (ATM) kinase is a central component involved in the signal transduction of the DNA damage response (DDR) and thus plays a critical role in the maintenance of genomic integrity. Although the primary functions of ATM are associated with the DDR, emerging data suggest that ATM has many additional roles that are not directly related to the DDR, including the regulation of oxidative stress signaling, insulin sensitivity, mitochondrial homeostasis, and lymphocyte development. Patients and mice lacking ATM exhibit growth retardation and lower bone mass; however, the mechanisms underlying the skeletal defects are not fully understood. In the present study, we generated mutant mice in which ATM is specifically inactivated in osteoclasts. The mutant mice did not exhibit apparent developmental defects but showed reduced bone mass due to increased osteoclastic bone resorption. Osteoclasts lacking ATM were more resistant to apoptosis and showed a prolonged lifespan compared to the controls. Notably, the inactivation of ATM in osteoclasts resulted in enhanced NF-κB signaling and an increase in the expression of NF-κB-targeted genes. The present study reveals a novel function for ATM in regulating bone metabolism by suppressing the lifespan of osteoclasts and osteoclast-mediated bone resorption.

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

    Science.gov (United States)

    Xie, Kan; Neff, Frauke; Markert, Astrid; Rozman, Jan; Aguilar-Pimentel, Juan Antonio; Amarie, Oana Veronica; Becker, Lore; Brommage, Robert; Garrett, Lillian; Henzel, Kristin S; Hölter, Sabine M; Janik, Dirk; Lehmann, Isabelle; Moreth, Kristin; Pearson, Brandon L; Racz, Ildiko; Rathkolb, Birgit; Ryan, Devon P; Schröder, Susanne; Treise, Irina; Bekeredjian, Raffi; Busch, Dirk H; Graw, Jochen; Ehninger, Gerhard; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Sandholzer, Michael; Schmidt-Weber, Carsten; Weiergräber, Marco; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Gailus-Durner, Valerie; Fuchs, Helmut; Hrabě de Angelis, Martin; Ehninger, Dan

    2017-07-24

    Dietary restriction regimes extend lifespan in various animal models. Here we show that longevity in male C57BL/6J mice subjected to every-other-day feeding is associated with a delayed onset of neoplastic disease that naturally limits lifespan in these animals. We compare more than 200 phenotypes in over 20 tissues in aged animals fed with a lifelong every-other-day feeding or ad libitum access to food diet to determine whether molecular, cellular, physiological and histopathological aging features develop more slowly in every-other-day feeding mice than in controls. We also analyze the effects of every-other-day feeding on young mice on shorter-term every-other-day feeding or ad libitum to account for possible aging-independent restriction effects. Our large-scale analysis reveals overall only limited evidence for a retardation of the aging rate in every-other-day feeding mice. The data indicate that every-other-day feeding-induced longevity is sufficiently explained by delays in life-limiting neoplastic disorders and is not associated with a more general slowing of the aging process in mice.Dietary restriction can extend the life of various model organisms. Here, Xie et al. show that intermittent periods of fasting achieved through every-other-day feeding protect mice against neoplastic disease but do not broadly delay organismal aging in animals.

  18. Availability of Amino Acids Extends Chronological Lifespan by Suppressing Hyper-Acidification of the Environment in Saccharomyces cerevisiae.

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    Yo Maruyama

    Full Text Available The chronological lifespan of Saccharomyces cerevisiae represents the duration of cell survival in the postdiauxic and stationary phases. Using a prototrophic strain derived from the standard auxotrophic laboratory strain BY4742, we showed that supplementation of non-essential amino acids to a synthetic defined (SD medium increases maximal cell growth and extends the chronological lifespan. The positive effects of amino acids can be reproduced by modulating the medium pH, indicating that amino acids contribute to chronological longevity in a cell-extrinsic manner by alleviating medium acidification. In addition, we showed that the amino acid-mediated effects on extension of chronological longevity are independent of those achieved through a reduction in the TORC1 pathway, which is mediated in a cell-intrinsic manner. Since previous studies showed that extracellular acidification causes mitochondrial dysfunction and leads to cell death, our results provide a path to premature chronological aging caused by differences in available nitrogen sources. Moreover, acidification of culture medium is generally associated with culture duration and cell density; thus, further studies are required on cell physiology of auxotrophic yeast strains during the stationary phase because an insufficient supply of essential amino acids may cause alterations in environmental conditions.

  19. Curcumin Stimulates Biochemical Mechanisms of Apis Mellifera Resistance and Extends the Apian Life-Span

    Directory of Open Access Journals (Sweden)

    Strachecka Aneta J.

    2015-06-01

    Full Text Available We examined the influence of curcumin-supplemented feeding on worker lifespan, Nosema resistance, key enzyme activities, metabolic compound concentrations and percentage of the global DNA methylation. Two worker groups (Apis mellifera were set up: 1 control group; workers were fed ad libitum with sucrose syrup; 2 workers were fed with the syrup with the addition of curcumin. Dead workers were removed every two days and the Nosema spp. infection levels were assessed. Hemolymph was taken from living workers for biochemical analyses. The global DNA methylation level was analysed using DNA from worker heads and thoraces. The bees that consumed curcumin lived longer and were less infested with Nosema spp. The curcumin-treated workers had higher concentrations of proteins, non-enzymatic biomarkers (triglycerides, glucose, cholesterol, Mg2+ and Ca2+, uric acid and creatinine, as well as elevated activities of antioxidant enzymes (SOD , GPx, CAT , GST , neutral proteases, protease inhibitors, enzymatic biomarkers (AST , ALT , ALP . The concentrations of albumin and urea, and the activities of acidic and alkaline proteases were higher in the control group. Curcumin decreased global DNA methylation levels especially in older bees in which the natural, age-related level increase was observed. Most of the parameters increased over the apian youth and adulthood, and decreased in older bees. The decrease was markedly delayed in the bees fed with curcumin. Curcumin appeared to be an unexpectedly effective natural bio-stimulator, improving apian health and vitality. This multifactorial effect is caused by the activation of many biochemical processes involved in the formation of apian resistance.

  20. APF530 (granisetron injection extended-release) in a three-drug regimen for delayed CINV in highly emetogenic chemotherapy.

    Science.gov (United States)

    Schnadig, Ian D; Agajanian, Richy; Dakhil, Christopher; Gabrail, Nashat Y; Smith, Robert E; Taylor, Charles; Wilks, Sharon T; Schwartzberg, Lee S; Cooper, William; Mosier, Michael C; Payne, J Yvette; Klepper, Michael J; Vacirca, Jeffrey L

    2016-06-01

    APF530, extended-release granisetron, provides sustained release for ≥5 days for acute- and delayed-phase chemotherapy-induced nausea and vomiting (CINV). We compared efficacy and safety of APF530 versus ondansetron for delayed CINV after highly emetogenic chemotherapy (HEC), following a guideline-recommended three-drug regimen. HEC patients received APF530 500 mg subcutaneously or ondansetron 0.15 mg/kg intravenously, with dexamethasone and fosaprepitant. Primary end point was delayed-phase complete response (no emesis or rescue medication). A higher percentage of APF530 versus ondansetron patients had delayed-phase complete response (p = 0.014). APF530 was generally well tolerated; treatment-emergent adverse event incidence was similar across arms, mostly mild-to-moderate injection-site reactions. APF530 versus the standard three-drug regimen provided superior control of delayed-phase CINV following HEC. ClinicalTrials.gov : NCT02106494.

  1. Emodin extends lifespan of Caenorhabditis elegans through insulin/IGF-1 signaling pathway depending on DAF-16 and SIR-2.1.

    Science.gov (United States)

    Zhao, Xuan; Lu, Lulu; Qi, Yonghao; Li, Miao; Zhou, Lijun

    2017-10-01

    The naturally occurring anthraquinone emodin has been serving primarily as an anti-bacterial and anti-inflammatory agent. However, little is known about its potential on anti-aging. This investigation examined the effect of emodin on lifespan and focused on its physiological molecular mechanisms in vivo. Using Caenorhabditis elegans (C. elegans) as an animal model, we found emodin could extend lifespan of worms and improve their antioxidant capacity. Our mechanistic studies revealed that emodin might function via insulin/IGF-1 signaling (IIS) pathway involving, specifically the core transcription factor DAF-16. Quantitative RT-PCR results illustrated that emodin up-regulated transcription of DAF-16 target genes which express antioxidants to promote antioxidant capacity and lifespan of worms. In addition, attenuated effect in sir-2.1 mutants suggests that emodin likely functioned in a SIR-2.1-dependent manner. Our study uncovers a novel role of emodin in prolonging lifespan and supports the understanding of emodin being a beneficial dietary supplement.

  2. Efficacy and safety of a flexible extended regimen of ethinylestradiol/drospirenone for the treatment of dysmenorrhea: a multicenter, randomized, open-label, active-controlled study

    Directory of Open Access Journals (Sweden)

    Momoeda M

    2017-05-01

    Full Text Available Mikio Momoeda,1 Masami Kondo,2 Joerg Elliesen,3 Masanobu Yasuda,2 Shigetomo Yamamoto,4 Tasuku Harada5 1Department of Integrated Women’s Health, St Luke’s International Hospital, Tokyo, 2Product Development, Bayer Yakuhin Ltd, Osaka, Japan; 3Global Clinical Development, Bayer AG, Berlin, Germany; 4Medical Affairs, Bayer Yakuhin Ltd, Osaka, 5Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Tottori, Japan Background: Dysmenorrhea is a common condition in women, which is characterized by menstrual pain. Low-dose estrogen/progestin combined oral contraceptives have been shown to reduce the severity of dysmenorrhea symptoms, and a 28-day cyclic regimen of ethinylestradiol/drospirenone (28d regimen is approved for this indication in Japan. Aim: The aim of this study was to assess the safety and efficacy of a flexible extended regimen of ethinylestradiol/drospirenone (flexible regimen in Japanese women with dysmenorrhea. Methods: This multicenter, open-label study was performed in Japanese women with dysmenorrhea who, after a baseline observational phase, were randomized to receive ethinylestradiol 20 µg/drospirenone 3 mg in a flexible regimen (one tablet each day for 24–120 days followed by a 4-day tablet-free interval or in the standard 28d regimen (one tablet each day for 24 days, followed by 4 days of placebo tablets for six cycles. The primary endpoint was the number of days with dysmenorrhea of at least mild intensity over a 140-day evaluation period. Dysmenorrhea scores, bleeding patterns, and other pain-related parameters were also assessed. Results: A total of 216 women (mean age 29.7 years were randomized to the flexible regimen (n=108 or 28d regimen (n=108 and 212 were included in the full analysis sets (flexible regimen, n=105; 28d regimen, n=107. Women in the flexible-regimen group reported a mean of 3.4 fewer days with dysmenorrheic pain than women in the 28d-regimen group, with similar decreases in

  3. Effects of fluctuating temperature and food availability on reproduction and lifespan.

    Science.gov (United States)

    Schwartz, Tonia S; Pearson, Phillip; Dawson, John; Allison, David B; Gohlke, Julia M

    2016-12-15

    Experimental studies on energetics and aging often remove two major factors that in part regulate the energy budget in a normal healthy individual: reproduction and fluctuating environmental conditions that challenge homeostasis. Here we use the cyclical parthenogenetic Daphnia pulex to evaluate the role of a fluctuating thermal environment on both reproduction and lifespan across six food concentrations. We test the hypotheses that (1) caloric restriction extends lifespan; (2) maximal reproduction will come with a cost of shortened lifespan; and (3) at a given food concentration, relative to a metabolically equivalent constant temperature environment a diel fluctuating thermal environment will alter the allocation of energy to reproduction and lifespan to maintain homeostasis. We did not identify a level of food concentration that extended lifespan in response to caloric restriction, and we found no cost of reproduction in terms of lifespan. Rather, the individuals at the highest food levels generally had the highest reproductive output and the longest lifespans, the individuals at the intermediate food level decreased reproduction and maintained lifespan, and the individuals at the three lower food concentrations had a decrease in reproduction and lifespan as would be predicted with increasing levels of starvation. Fluctuating temperature had no effect on lifespan at any food concentration, but delayed time to reproductive maturity and decreased early reproductive output at all food concentrations. This suggests that a fluctuating temperature regimen activates molecular pathways that alter energy allocation. The costs of fluctuating temperature on reproduction were not consistent across the lifespan. Statistical interactions for age of peak reproduction and lifetime fecundity suggest that senescence of the reproductive system may vary between temperature regimens at the different food concentrations. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Switching from pro re nata to treat-and-extend regimen improves visual acuity in patients with neovascular age-related macular degeneration.

    Science.gov (United States)

    Kvannli, Line; Krohn, Jørgen

    2017-11-01

    To evaluate the visual outcome after transitioning from a pro re nata (PRN) intravitreal injection regimen to a treat-and-extend (TAE) regimen for patients with neovascular age-related macular degeneration (AMD). A retrospective review of patients who were switched from a PRN regimen with intravitreal injections of bevacizumab, ranibizumab or aflibercept to a TAE regimen. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and type of medication used at baseline, at the time of changing treatment regimen and at the end of the study were analysed. Twenty-one eyes of 21 patients met the inclusion criteria. Prior to the switch, the patients received a mean of 13.8 injections (median, 10; range, 3-39 injections) with the PRN regimen for 44 months (range, 3-100 months), which improved the visual acuity in five patients (24%). After a mean of 6.1 injections (median, 5; range, 3-14 injections) with the TAE regimen over 8 months (range, 2-16 months), the visual acuity improved in 12 patients (57%). The improvement in visual acuity during treatment with the TAE regimen was statistically significant (p = 0.005). The proportion of patients with a visual acuity of 0.2 or better was significantly higher after treatment with the TAE regimen than after treatment with the PRN regimen (p = 0.048). No significant differences in CRT were found between the two treatment regimens. Even after prolonged treatment and a high number of intravitreal injections, switching AMD patients from a PRN regimen to a strict TAE regimen significantly improves visual acuity. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  5. Polyphenol-Rich Diets Exacerbate AMPK-Mediated Autophagy, Decreasing Proliferation of Mosquito Midgut Microbiota, and Extending Vector Lifespan.

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    Rodrigo Dutra Nunes

    2016-10-01

    Full Text Available Mosquitoes feed on plant-derived fluids such as nectar and sap and are exposed to bioactive molecules found in this dietary source. However, the role of such molecules on mosquito vectorial capacity is unknown. Weather has been recognized as a major determinant of the spread of dengue, and plants under abiotic stress increase their production of polyphenols.Here, we show that including polyphenols in mosquito meals promoted the activation of AMP-dependent protein kinase (AMPK. AMPK positively regulated midgut autophagy leading to a decrease in bacterial proliferation and an increase in vector lifespan. Suppression of AMPK activity resulted in a 6-fold increase in midgut microbiota. Similarly, inhibition of polyphenol-induced autophagy induced an 8-fold increase in bacterial proliferation. Mosquitoes maintained on the polyphenol diet were readily infected by dengue virus.The present findings uncover a new direct route by which exacerbation of autophagy through activation of the AMPK pathway leads to a more efficient control of mosquito midgut microbiota and increases the average mosquito lifespan. Our results suggest for the first time that the polyphenol content and availability of the surrounding vegetation may increase the population of mosquitoes prone to infection with arboviruses.

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

    DEFF Research Database (Denmark)

    Xie, Kan; Neff, Frauke; Markert, Astrid

    2017-01-01

    that every-other-day feeding-induced longevity is sufficiently explained by delays in life-limiting neoplastic disorders and is not associated with a more general slowing of the aging process in mice.Dietary restriction can extend the life of various model organisms. Here, Xie et al. show that intermittent...... periods of fasting achieved through every-other-day feeding protect mice against neoplastic disease but do not broadly delay organismal aging in animals....

  7. Running on empty: does mitochondrial DNA mutation limit replicative lifespan in yeast?: Mutations that increase the division rate of cells lacking mitochondrial DNA also extend replicative lifespan in Saccharomyces cerevisiae.

    Science.gov (United States)

    Dunn, Cory D

    2011-10-01

    Mitochondrial DNA (mtDNA) mutations escalate with increasing age in higher organisms. However, it has so far been difficult to experimentally determine whether mtDNA mutation merely correlates with age or directly limits lifespan. A recent study shows that budding yeast can also lose functional mtDNA late in life. Interestingly, independent studies of replicative lifespan (RLS) and of mtDNA-deficient cells show that the same mutations can increase both RLS and the division rate of yeast lacking the mitochondrial genome. These exciting, parallel findings imply a potential causal relationship between mtDNA mutation and replicative senescence. Furthermore, these results suggest more efficient methods for discovering genes that determine lifespan. Copyright © 2011 WILEY Periodicals, Inc.

  8. Glycation inhibitors extend yeast chronological lifespan by reducing advanced glycation end products and by back regulation of proteins involved in mitochondrial respiration.

    Science.gov (United States)

    Kazi, Rubina S; Banarjee, Reema M; Deshmukh, Arati B; Patil, Gouri V; Jagadeeshaprasad, Mashanipalya G; Kulkarni, Mahesh J

    2017-03-06

    Advanced Glycation End products (AGEs) are implicated in aging process. Thus, reducing AGEs by using glycation inhibitors may help in attenuating the aging process. In this study using Saccharomyces cerevisiae yeast system, we show that Aminoguanidine (AMG), a well-known glycation inhibitor, decreases the AGE modification of proteins in non-calorie restriction (NR) (2% glucose) and extends chronological lifespan (CLS) similar to that of calorie restriction (CR) condition (0.5% glucose). Proteomic analysis revealed that AMG back regulates the expression of differentially expressed proteins especially those involved in mitochondrial respiration in NR condition, suggesting that it switches metabolism from fermentation to respiration, mimicking CR. AMG induced back regulation of differentially expressed proteins could be possibly due to its chemical effect or indirectly by glycation inhibition. To delineate this, Metformin (MET), a structural analog of AMG and a mild glycation inhibitor and Hydralazine (HYD), another potent glycation inhibitor but not structural analog of AMG were used. HYD was more effective than MET in mimicking AMG suggesting that glycation inhibition was responsible for restoration of differentially expressed proteins. Thus glycation inhibitors particularly AMG, HYD and MET extend yeast CLS by reducing AGEs, modulating the expression of proteins involved in mitochondrial respiration and possibly by scavenging glucose. This study reports the role of glycation in aging process. In the non-caloric restriction condition, carbohydrates such as glucose promote protein glycation and reduce CLS. While, the inhibitors of glycation such as AMG, HYD, MET mimic the caloric restriction condition by back regulating deregulated proteins involved in mitochondrial respiration which could facilitate shift of metabolism from fermentation to respiration and extend yeast CLS. These findings suggest that glycation inhibitors can be potential molecules that can be used

  9. 10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling

    OpenAIRE

    Honda, Yoko; Araki, Yoko; Hata, Taketoshi; Ichihara, Kenji; Ito, Masafumi; Tanaka, Masashi; Honda, Shuji

    2015-01-01

    Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA f...

  10. Behavioral Senescence and Aging-Related Changes in Motor Neurons and Brain Neuromodulator Levels Are Ameliorated by Lifespan-Extending Reproductive Dormancy in Drosophila

    Directory of Open Access Journals (Sweden)

    Dick R. Nässel

    2017-04-01

    Full Text Available The lifespan of Drosophilamelanogaster can be extended substantially by inducing reproductive dormancy (also known as diapause by lowered temperature and short days. This increase of longevity is accompanied by lowered metabolism and increased stress tolerance. We ask here whether behavioral senescence is ameliorated during adult dormancy. To study this we kept flies for seven or more weeks in normal rearing conditions or in diapause conditions and compared to 1-week-old flies in different behavioral assays of sleep, negative geotaxis and exploratory walking. We found that the senescence of geotaxis and locomotor behavior seen under normal rearing conditions was negligible in flies kept in dormancy. The normal senescence of rhythmic activity and sleep patterns during the daytime was also reduced by adult dormancy. Investigating the morphology of specific neuromuscular junctions (NMJs, we found that changes normally seen with aging do not take place in dormant flies. To monitor age-associated changes in neuronal circuits regulating activity rhythms, sleep and walking behavior we applied antisera to tyrosine hydroxylase (TH, serotonin and several neuropeptides to examine changes in expression levels and neuron morphology. In most neuron types the levels of stored neuromodulators decreased during normal aging, but not in diapause treated flies. No signs of neurodegeneration were seen in either condition. Our data suggest that age-related changes in motor neurons could be the cause of part of the behavioral senescence and that this is ameliorated by reproductive diapause. Earlier studies established a link between age-associated decreases in neuromodulator levels and behavioral decline that could be rescued by overexpression of neuromodulator. Thus, it is likely that the retained levels of neuromodulators in dormant flies alleviate behavioral senescence.

  11. Animal lifespan and human influence

    Science.gov (United States)

    Guo, Q.; Yang, S.

    2002-01-01

    Lifespan differs radically among organisms ever lived on earth, even among those roughly similar in size, shape, form, and physiology; Yet, in general, there exists a strong positive relationship between lifespan and body size. Although lifespans of humans and human-related (domestic) animals are becoming increasingly longer than that of other animals of similar sizes, the slope of the regression (lifespan-body size) line and the intercepts have been surprisingly stable over the course of the dramatic human population growth, indicating substantial depression in lifespans of many other animals probably due to shrunk and fragmented natural habitats. This article addresses two questions related to the lifespan-size relationship: (1) what caused the exceptions (e.g., a few remote human-related animals are also located above the regression line with great residuals) and why (e.g., could brain size or intelligence be a covariate in addition to body size in predicting lifespan?), and (2) whether continued human activities can eventually alter the ' natural' regression line in the future, and if so, how much. We also suggest similar research efforts to be extended to the plant world as well.

  12. Efficacy of extended clomifene citrate regimen in comparison with gonadotropins in clomifene citrate-resistant women with polycystic ovary syndrome

    OpenAIRE

    Mahmoud Fathy Hassan

    2014-01-01

    Background: Gonadotropins are successful treatment for women with clomifene citrate (CC)-resistant polycystic ovary syndrome (PCOS). The aim of this study was to test the hypothesis that extended CC treatment may be an alternative to gonadotropins in the management of CC-resistant women with PCOS. Methods: A randomized controlled trial comprised 200 women with CC-resistant PCOS were allocated to two equal treatment groups. Patients in the CC group were given 100 mg of CC daily starting fr...

  13. Two-Year Outcomes of a Treat-and-Extend Regimen Using Intravitreal Aflibercept Injections for Typical Age-Related Macular Degeneration.

    Science.gov (United States)

    Ito, Arisa; Matsumoto, Hidetaka; Morimoto, Masahiro; Mimura, Kensuke; Akiyama, Hideo

    2017-01-01

    The aim of this study was to evaluate the efficacy of a treat-and-extend (TAE) regimen using intravitreal injection of aflibercept (IVA) for typical age-related macular degeneration (tAMD). We retrospectively studied 61 treatment-naïve eyes with tAMD. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), number of injections, and complications during 2 years were evaluated. BCVA significantly improved by on average 0.13 logMAR units, and CMT and CCT significantly decreased after 2 years. The number of injections was on average 13.6. In the second year, eyes with classic choroidal neovascularization (CNV) needed significantly fewer treatments than eyes with occult CNV. Fourteen eyes, which developed subfoveal fibrosis, showed significantly poorer BCVA after 2 years. Subfoveal fibrosis was significantly common in classic CNV. A TAE regimen using IVA for tAMD might be effective for improving BCVA and exudative changes. The exudation may be suppressed with fewer treatments in classic CNV compared to occult CNV. © 2017 S. Karger AG, Basel.

  14. The long-term effects of a life-prolonging heat treatment on the Drosophila melanogaster transcriptome suggest that heat shock proteins extend lifespan

    DEFF Research Database (Denmark)

    Sarup, Pernille Merete; Sørensen, Peter; Loeschcke, Volker

    2014-01-01

    Heat-induced hormesis, i.e. the beneficial effect of mild heat-induced stress, increases the average lifespan of many organisms. This effect, which depends on the heat shock factor, decreases the log mortality rate weeks after the stress has ceased. To identify candidate genes that mediate......-treated flies. Several hsp70 probe sets were up-regulated 1.7–2-fold in the mildly stressed flies weeks after the last heat treatment (P shock protein, Hsp70, is reported to return to normal levels of expression shortly after heat stress. We...... conclude that the heat shock response, and Hsp70 in particular, may be central to the heat-induced increase in the average lifespan in flies that are exposed to mild heat stress early in life....

  15. Efficacy of treat-and-extend regimen with aflibercept for pachychoroid neovasculopathy and Type 1 neovascular age-related macular degeneration.

    Science.gov (United States)

    Matsumoto, Hidetaka; Hiroe, Takashi; Morimoto, Masahiro; Mimura, Kensuke; Ito, Arisa; Akiyama, Hideo

    2018-03-01

    To evaluate the efficacy of intravitreal aflibercept therapy using a treat-and-extend regimen on treatment-naïve pachychoroid neovasculopathy (PNV) and Type 1 neovascular age-related macular degeneration (AMD). We retrospectively studied 42 eyes with PNV and 60 eyes with Type 1 neovascular AMD. We assessed best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and total number of injections over 2 years. The BCVA and CMT improvements during the 2-year treatment period did not differ significantly between PNV and AMD; however, CCT decreased significantly in PNV than in AMD (P<0.05). Management of PNV required significantly fewer injections than AMD during the 2-year period (P<0.05). There were no significant differences in BCVA, CMT and CCT changes between PNV with and without polypoidal lesions (28 vs. 14 eyes) during the 2 year period. Significantly fewer injections were needed for PNV with polypoidal lesions than for PNV without (P<0.01). There were no significant differences in BCVA, CMT and CCT changes, or in the number of injections during the 2-year treatment period, between AMD with and without polypoidal lesions (30 vs. 30 eyes). Treat-and-extend regimen of intravitreal aflibercept injection may be equally effective in terms of improvement of BCVA and exudative changes both in eyes with PNV and those with Type 1 neovascular AMD requiring fewer injections for the former. Among eyes with PNV, those with polypoidal lesions needed fewer injections than those without polypoidal lesions.

  16. Long-Term Visual Outcomes for a Treat and Extend Anti-Vascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Sarah Mrejen

    2015-07-01

    Full Text Available With the advent of anti-vascular endothelial growth factor (VEGF therapy, clinicians are now focused on various treatment strategies to better control neovascular age-related macular degeneration (NVAMD, a leading cause of irreversible blindness. Herein, we retrospectively reviewed consecutive patients with treatment-naïve NVAMD initially classified based on fluorescein angiography (FA alone or with an anatomic classification utilizing both FA and optical coherence tomography (OCT and correlated long-term visual outcomes of these patients treated with an anti-VEGF Treat-and-Extend Regimen (TER with baseline characteristics including neovascular phenotype. Overall, 185 patients (210 eyes were followed over an average of 3.5 years (range 1–6.6 with a retention rate of 62.9%, and visual acuity significantly improved with a TER that required a mean number of 8.3 (±1.6 (± standard deviation intravitreal anti-VEGF injections/year (range 4–13. The number of injections and the anatomic classification were independent predictors of visual acuity at 6 months, 1, 2, 3 and 4 years. Patients with Type 1 neovascularization had better visual outcomes and received more injections than the other neovascular subtypes. There were no serious adverse events. A TER provided sustained long-term visual gains. Eyes with Type 1 neovascularization had better visual outcomes than those with other neovascular subtypes.

  17. A high-fat jelly diet restores bioenergetic balance and extends lifespan in the presence of motor dysfunction and lumbar spinal cord motor neuron loss in TDP-43A315T mutant C57BL6/J mice

    Directory of Open Access Journals (Sweden)

    Karen S. Coughlan

    2016-09-01

    Full Text Available Transgenic transactivation response DNA-binding protein 43 (TDP-43 mice expressing the A315T mutation under control of the murine prion promoter progressively develop motor function deficits and are considered a new model for the study of amyotrophic lateral sclerosis (ALS; however, premature sudden death resulting from intestinal obstruction halts disease phenotype progression in 100% of C57BL6/J congenic TDP-43A315T mice. Similar to our recent results in SOD1G93A mice, TDP-43A315T mice fed a standard pellet diet showed increased 5′ adenosine monophosphate-activated protein kinase (AMPK activation at postnatal day (P80, indicating elevated energetic stress during disease progression. We therefore investigated the effects of a high-fat jelly diet on bioenergetic status and lifespan in TDP-43A315T mice. In contrast to standard pellet-fed mice, mice fed high-fat jelly showed no difference in AMPK activation up to P120 and decreased phosphorylation of acetly-CoA carboxylase (ACC at early-stage time points. Exposure to a high-fat jelly diet prevented sudden death and extended survival, allowing development of a motor neuron disease phenotype with significantly decreased body weight from P80 onward that was characterised by deficits in Rotarod abilities and stride length measurements. Development of this phenotype was associated with a significant motor neuron loss as assessed by Nissl staining in the lumbar spinal cord. Our work suggests that a high-fat jelly diet improves the pre-clinical utility of the TDP-43A315T model by extending lifespan and allowing the motor neuron disease phenotype to progress, and indicates the potential benefit of this diet in TDP-43-associated ALS.

  18. Autism through the Lifespan

    Science.gov (United States)

    ... Information Publications Awards Partners Contact Us ¿Qué es Autismo? Donate Home What is Autism? What is Autism? ... Information Publications Awards Partners Contact Us ¿Qué es Autismo? Autism through the Lifespan Home / Living with Autism / ...

  19. Extending the Lifespan of Porous Asphalt Concrete

    NARCIS (Netherlands)

    Zhang, Y.

    2015-01-01

    Porous Asphalt (PA) concrete is widely used as a surfacing layer on highways in the Netherlands. The service life of PA wearing courses is limited because of the fact that it is vulnerable to raveling. The possibilities of applying preventive maintenance to PA wearing courses by means of spraying

  20. The Lifespan of Ornaments

    DEFF Research Database (Denmark)

    Munch, Anders V.; Riisberg, Vibeke

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

  1. Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A.

    Science.gov (United States)

    Závada, J; Sinikka Pesicková, S; Rysavá, R; Horák, P; Hrncír, Z; Lukác, J; Rovensky, J; Vítová, J; Havrda, M; Rychlík, I; Böhmova, J; Vlasáková, V; Slatinská, J; Zadrazil, J; Olejárová, M; Tegzova, D; Tesar, V

    2014-01-01

    Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term.

  2. Measurement of lifespan in Drosophila melanogaster.

    Science.gov (United States)

    Linford, Nancy J; Bilgir, Ceyda; Ro, Jennifer; Pletcher, Scott D

    2013-01-07

    Aging is a phenomenon that results in steady physiological deterioration in nearly all organisms in which it has been examined, leading to reduced physical performance and increased risk of disease. Individual aging is manifest at the population level as an increase in age-dependent mortality, which is often measured in the laboratory by observing lifespan in large cohorts of age-matched individuals. Experiments that seek to quantify the extent to which genetic or environmental manipulations impact lifespan in simple model organisms have been remarkably successful for understanding the aspects of aging that are conserved across taxa and for inspiring new strategies for extending lifespan and preventing age-associated disease in mammals. The vinegar fly, Drosophila melanogaster, is an attractive model organism for studying the mechanisms of aging due to its relatively short lifespan, convenient husbandry, and facile genetics. However, demographic measures of aging, including age-specific survival and mortality, are extraordinarily susceptible to even minor variations in experimental design and environment, and the maintenance of strict laboratory practices for the duration of aging experiments is required. These considerations, together with the need to practice careful control of genetic background, are essential for generating robust measurements. Indeed, there are many notable controversies surrounding inference from longevity experiments in yeast, worms, flies and mice that have been traced to environmental or genetic artifacts(1-4). In this protocol, we describe a set of procedures that have been optimized over many years of measuring longevity in Drosophila using laboratory vials. We also describe the use of the dLife software, which was developed by our laboratory and is available for download (http://sitemaker.umich.edu/pletcherlab/software). dLife accelerates throughput and promotes good practices by incorporating optimal experimental design, simplifying

  3. Changes in Regenerative Capacity through Lifespan

    Directory of Open Access Journals (Sweden)

    Maximina H. Yun

    2015-10-01

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

  4. Ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen for the management of endometriosis-associated pelvic pain: a randomized controlled trial.

    Science.gov (United States)

    Harada, Tasuku; Kosaka, Saori; Elliesen, Joerg; Yasuda, Masanobu; Ito, Makoto; Momoeda, Mikio

    2017-11-01

    To investigate the efficacy and safety of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen (Flexible MIB ) compared with placebo to treat endometriosis-associated pelvic pain (EAPP). A phase 3, randomized, double-blind, placebo-controlled, parallel-group study, consisting of a 24-week double-blind treatment phase followed by a 28-week open-label extension phase with an unblinded reference arm. Thirty-two centers. A total of 312 patients with endometriosis. Patients were randomized to Flexible MIB , placebo, or dienogest. The Flexible MIB and placebo arms received 1 tablet per day continuously for 120 days, with a 4-day tablet-free interval either after 120 days or after ≥3 consecutive days of spotting and/or bleeding on days 25-120. After 24 weeks, placebo recipients were changed to Flexible MIB . Patients randomized to dienogest received 2 mg/d for 52 weeks in an unblinded reference arm. Absolute change in the most severe EAPP based on visual analog scale scores from the baseline observation phase to the end of the double-blind treatment phase. Compared with placebo, Flexible MIB significantly reduced the most severe EAPP (mean difference in visual analog scale score: -26.3 mm). Flexible MIB also improved other endometriosis-associated pain and gynecologic findings and reduced the size of endometriomas. Flexible MIB improved EAPP and was well tolerated, suggesting it may be a new alternative for managing endometriosis. NCT01697111. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Listening comprehension across the adult lifespan.

    Science.gov (United States)

    Sommers, Mitchell S; Hale, Sandra; Myerson, Joel; Rose, Nathan; Tye-Murray, Nancy; Spehar, Brent

    2011-01-01

    Although age-related declines in perceiving spoken language are well established, the primary focus of research has been on perception of phonemes, words, and sentences. In contrast, relatively few investigations have been directed at establishing the effects of age on the comprehension of extended spoken passages. Moreover, most previous work has used extreme-group designs in which the performance of a group of young adults is contrasted with that of a group of older adults and little if any information is available regarding changes in listening comprehension across the adult lifespan. Accordingly, the goals of the current investigation were to determine whether there are age differences in listening comprehension across the adult lifespan and, if so, whether similar trajectories are observed for age-related changes in auditory sensitivity and listening comprehension. This study used a cross-sectional lifespan design in which approximately 60 individuals in each of 7 decades, from age 20 to 89 yr (a total of 433 participants), were tested on three different measures of listening comprehension. In addition, we obtained measures of auditory sensitivity from all participants. Changes in auditory sensitivity across the adult lifespan exhibited the progressive high-frequency loss typical of age-related hearing impairment. Performance on the listening comprehension measures, however, demonstrated a very different pattern, with scores on all measures remaining relatively stable until age 65 to 70 yr, after which significant declines were observed. Follow-up analyses indicated that this same general pattern was observed across three different types of passages (lectures, interviews, and narratives) and three different question types (information, integration, and inference). Multiple regression analyses indicated that low-frequency pure-tone average was the single largest contributor to age-related variance in listening comprehension for individuals older than 65 yr, but

  6. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T

    2015-01-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...

  7. The role of MAP4K3 in lifespan regulation of Caenorhabditiselegans

    International Nuclear Information System (INIS)

    Khan, Maruf H.; Hart, Matthew J.; Rea, Shane L.

    2012-01-01

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

  8. The role of MAP4K3 in lifespan regulation of Caenorhabditiselegans

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-08-24

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

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

    Directory of Open Access Journals (Sweden)

    Janne M Toivonen

    2007-06-01

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

  10. Cortical Changes Across the Autism Lifespan.

    Science.gov (United States)

    Osipowicz, Karol; Bosenbark, Danielle D; Patrick, Kristina E

    2015-08-01

    Although it is widely accepted that autism spectrum disorder (ASD) involves neuroanatomical abnormalities and atypical neurodevelopmental patterns, there is little consensus regarding the precise pattern of neuroanatomical differences or how these differences relate to autism symptomology. Furthermore, there is limited research related to neuroanatomical correlates of autism symptomology in individuals with ASD and the studies that do exist primarily include small samples. This study was the first to investigate gray matter (GM) changes throughout the ASD lifespan, using voxel-based morphometry to determine whether significant differences exist in the GM volumes of a large sample of individuals with ASD compared to age- and IQ-matched typical controls. We examined GM volume across the lifespan in 531 individuals diagnosed with ASD and 571 neurotypical controls, aged 7-64. We compared groups and correlated GM with age and autism severity in the ASD group. Findings suggest bilateral decreased GM volume for individuals with ASD in regions extending from the thalamus to the cerebellum, anterior medial temporal lobes, and orbitofrontal regions. Higher autism severity was associated with decreased GM volumes in prefrontal cortex, inferior parietal and temporal regions, and temporal poles. Similar relationships were found between GM volume and age. ASD diagnosis and severity were not associated with increased GM volumes in any region. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  11. Lifespan extension by preserving proliferative homeostasis in Drosophila.

    Directory of Open Access Journals (Sweden)

    Benoît Biteau

    2010-10-01

    Full Text Available Regenerative processes are critical to maintain tissue homeostasis in high-turnover tissues. At the same time, proliferation of stem and progenitor cells has to be carefully controlled to prevent hyper-proliferative diseases. Mechanisms that ensure this balance, thus promoting proliferative homeostasis, are expected to be critical for longevity in metazoans. The intestinal epithelium of Drosophila provides an accessible model in which to test this prediction. In aging flies, the intestinal epithelium degenerates due to over-proliferation of intestinal stem cells (ISCs and mis-differentiation of ISC daughter cells, resulting in intestinal dysplasia. Here we show that conditions that impair tissue renewal lead to lifespan shortening, whereas genetic manipulations that improve proliferative homeostasis extend lifespan. These include reduced Insulin/IGF or Jun-N-terminal Kinase (JNK signaling activities, as well as over-expression of stress-protective genes in somatic stem cell lineages. Interestingly, proliferative activity in aging intestinal epithelia correlates with longevity over a range of genotypes, with maximal lifespan when intestinal proliferation is reduced but not completely inhibited. Our results highlight the importance of the balance between regenerative processes and strategies to prevent hyperproliferative disorders and demonstrate that promoting proliferative homeostasis in aging metazoans is a viable strategy to extend lifespan.

  12. Extension of lifespan in C. elegans by naphthoquinones that act through stress hormesis mechanisms.

    Directory of Open Access Journals (Sweden)

    Piper R Hunt

    Full Text Available Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that can generate free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. The C. elegans cap'n'collar (CNC transcription factor, SKN-1, mediates protective responses to oxidative stress. Genetic analysis showed that skn-1 activity is required for lifespan extension by low-dose plumbagin in C. elegans. Further screening of a series of plumbagin analogs identified three additional naphthoquinones that could induce SKN-1 targets in C. elegans. Naphthazarin showed skn-1dependent lifespan extension, over an extended dose range compared to plumbagin, while the other naphthoquinones, oxoline and menadione, had differing effects on C. elegans survival and failed to activate ARE reporter expression in cultured mammalian cells. Our findings reveal the potential for low doses of naturally occurring naphthoquinones to extend lifespan by engaging a specific adaptive cellular stress response pathway.

  13. Workplace flexibility across the lifespan

    OpenAIRE

    Bal, Pieter; Jansen, Paul G W

    2016-01-01

    As demographic changes impact the workplace, governments, organizations and workers arelooking for ways to sustain optimal working lives at higher ages. Workplace flexibility has beenintroduced as a potential way workers can have more satisfying working lives until theirretirement ages. This paper presents a critical review of the literature on workplace flexibilityacross the lifespan. It discusses how flexibility has been conceptualized across differentdisciplines, and postulates a definitio...

  14. Effects of fluctuating temperature and food availability on reproduction and lifespan

    OpenAIRE

    Schwartz, Tonia S.; Pearson, Phillip; Dawson, John; Allison, David B.; Gohlke, Julia M.

    2016-01-01

    Experimental studies on energetics and aging often remove two major factors that in part regulate the energy budget in a normal healthy individual: reproduction and fluctuating environmental conditions that challenge homeostasis. Here we use the cyclical parthenogenetic Daphnia pulex to evaluate the role of a fluctuating thermal environment on both reproduction and lifespan across six food concentrations. We test the hypotheses that (1) caloric restriction extends lifespan; (2) maximal reprod...

  15. Nitrogen Ion Form and Spatio-temporal Variation in Root Distribution Mediate Nitrogen Effects on Lifespan of Ectomycorrhizal Roots

    Science.gov (United States)

    Kou, L.; McCormack, M. L.; Chen, W.; Guo, D.; Wang, H.; Li, S.; Gao, W.; Yang, H.

    2017-12-01

    Background and Aims Absorptive roots active in soil resource uptake are often intimately associated with mycorrhizal fungi, yet it remains unclear how nitrogen (N) loading affects lifespan of absorptive roots associating with ectomycorrhizal (ECM) fungi. Methods Through a three-year minirhizotron experiment, we investigated the responses of ECM lifespan to different rates of N addition and examined the roles of N ion form, rooting depth, seasonal root cohort, and ECM morphotype in mediating the N effects on ECM lifespan in a slash pine (Pinus elliottii) forest in subtropical China. Results High rates of NH4Cl significantly decreased foliar P concentrations and increased foliar N: P ratios, and mean ECM lifespan was negatively correlated to foliar P concentration. N additions generally increased the lifespan of most ectomycorrhizas, but the specific differences were context dependent. N rates and forms exerted significant positive effects on ECM lifespan with stronger effects occurring at high N rates and under ammonium N addition. N additions extended lifespan of ectomycorrhizas in shallower soil and born in spring and autumn, but shortened lifespan of ectomycorrhizas in deeper soil and born in summer and winter. N additions reduced lifespan of dichotomous ectomycorrhizas, but increased lifespan of coralloid ectomycorrhizas. Conclusions The increased ECM lifespan in response to N additions may primarily be driven by the persistent and aggravated P limitation to plants. Our findings highlight the importance of environmental contexts in controlling ECM lifespan and the need to consider potential differences among mycorrhizal morphotypes when studying N—lifespan relationships of absorptive roots in the context of N deposition.

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

    Directory of Open Access Journals (Sweden)

    Paola V Castro

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

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

    Science.gov (United States)

    Fierro-González, Juan Carlos; González-Barrios, María; Miranda-Vizuete, Antonio; Swoboda, Peter

    2011-03-18

    Dietary restriction (DR) is the only environmental intervention known to extend adult lifespan in a wide variety of animal models. However, the genetic and cellular events that mediate the anti-aging programs induced by DR remain elusive. Here, we used the nematode Caenorhabditis elegans to provide the first in vivo evidence that a thioredoxin (TRX-1) regulates adult lifespan extension induced by DR. We found that deletion of the gene trx-1 completely suppressed the lifespan extension caused by mutation of eat-2, a genetic surrogate of DR in the worm. However, trx-1 deletion only partially suppressed the long lifespan caused by mutation of the insulin-like receptor gene daf-2 or by mutation of the sensory cilia gene osm-5. A trx-1::GFP translational fusion expressed from its own promoter in ASJ neurons (Ptrx-1::trx-1::GFP) rescued the trx-1 deletion-mediated suppression of the lifespan extension caused by mutation of eat-2. This rescue was not observed when trx-1::GFP was expressed from the ges-1 promoter in the intestine. In addition, overexpression of Ptrx-1::trx-1::GFP extended lifespan in wild type, but not in eat-2 mutants. trx-1 deletion almost completely suppressed the lifespan extension induced by dietary deprivation (DD), a non-genetic, nutrient-based model of DR in the worm. Moreover, DD upregulated the expression of a trx-1 promoter-driven GFP reporter gene (Ptrx-1::GFP) in ASJ neurons of aging adults, but not that of control Pgpa-9::GFP (which is also expressed in ASJ neurons). We propose that DR activates TRX-1 in ASJ neurons during aging, which in turn triggers TRX-1-dependent mechanisms to extend adult lifespan in the worm. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. A Reduction in Age-Enhanced Gluconeogenesis Extends Lifespan

    OpenAIRE

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

    2013-01-01

    The regulation of energy metabolism, such as calorie restriction (CR), is a major determinant of cellular longevity. Although augmented gluconeogenesis is known to occur in aged yeast cells, the role of enhanced gluconeogenesis in aged cells remains undefined. Here, we show that age-enhanced gluconeogenesis is suppressed by the deletion of the tdh2 gene, which encodes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a protein that is involved in both glycolysis and gluconeogenesis in yeast c...

  19. Extending the lifespan of nuclear power plant structures

    International Nuclear Information System (INIS)

    Naus, D.J.; Oland, C.B.; Ellingwood, B.

    1995-01-01

    By the end of this decade, 63 of the 111 commercial nuclear power plants in the United States will be more than 20 years old, with some nearing the end of their 40-year operating license term. Faced with the prospect of having to replace lost generating capacity from other sources and substantial shutdown and decommissioning costs, many utilities are expected to apply to continue the service of their plants past the initial licensing period. In support of such applications, evidence should be provided that the capacity of the safety-related systems and structures to mitigate potential extreme events has not deteriorated unacceptably due to either aging or environmental stressor effects during the previous service history

  20. Development of antibiotic regimens using graph based evolutionary algorithms.

    Science.gov (United States)

    Corns, Steven M; Ashlock, Daniel A; Bryden, Kenneth M

    2013-12-01

    This paper examines the use of evolutionary algorithms in the development of antibiotic regimens given to production animals. A model is constructed that combines the lifespan of the animal and the bacteria living in the animal's gastro-intestinal tract from the early finishing stage until the animal reaches market weight. This model is used as the fitness evaluation for a set of graph based evolutionary algorithms to assess the impact of diversity control on the evolving antibiotic regimens. The graph based evolutionary algorithms have two objectives: to find an antibiotic treatment regimen that maintains the weight gain and health benefits of antibiotic use and to reduce the risk of spreading antibiotic resistant bacteria. This study examines different regimens of tylosin phosphate use on bacteria populations divided into Gram positive and Gram negative types, with a focus on Campylobacter spp. Treatment regimens were found that provided decreased antibiotic resistance relative to conventional methods while providing nearly the same benefits as conventional antibiotic regimes. By using a graph to control the information flow in the evolutionary algorithm, a variety of solutions along the Pareto front can be found automatically for this and other multi-objective problems. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Christina Greer

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

  2. Pomegranate juice enhances healthy lifespan in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Padmavathy eVenkatasubramanian

    2014-12-01

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

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

    International Nuclear Information System (INIS)

    Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-12-25

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

  5. A role for autophagy in the extension of lifespan by dietary restriction in C. elegans.

    Directory of Open Access Journals (Sweden)

    Malene Hansen

    2008-02-01

    Full Text Available In many organisms, dietary restriction appears to extend lifespan, at least in part, by down-regulating the nutrient-sensor TOR (Target Of Rapamycin. TOR inhibition elicits autophagy, the large-scale recycling of cytoplasmic macromolecules and organelles. In this study, we asked whether autophagy might contribute to the lifespan extension induced by dietary restriction in C. elegans. We find that dietary restriction and TOR inhibition produce an autophagic phenotype and that inhibiting genes required for autophagy prevents dietary restriction and TOR inhibition from extending lifespan. The longevity response to dietary restriction in C. elegans requires the PHA-4 transcription factor. We find that the autophagic response to dietary restriction also requires PHA-4 activity, indicating that autophagy is a transcriptionally regulated response to food limitation. In spite of the rejuvenating effect that autophagy is predicted to have on cells, our findings suggest that autophagy is not sufficient to extend lifespan. Long-lived daf-2 insulin/IGF-1 receptor mutants require both autophagy and the transcription factor DAF-16/FOXO for their longevity, but we find that autophagy takes place in the absence of DAF-16. Perhaps autophagy is not sufficient for lifespan extension because although it provides raw material for new macromolecular synthesis, DAF-16/FOXO must program the cells to recycle this raw material into cell-protective longevity proteins.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-04-01

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

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

    International Nuclear Information System (INIS)

    Kamei, Yuka; Tamura, Takayuki; Yoshida, Ryo; Ohta, Shinji; Fukusaki, Eiichiro; Mukai, Yukio

    2011-01-01

    Highlights: →We demonstrate that two genes in the yeast GABA metabolism pathway affect aging. → Deletion of the UGA1 or GAD1 genes extends replicative lifespan. → Addition of GABA to wild-type cultures has no effect on lifespan. → Intracellular GABA levels do not differ in longevity mutants and wild-type cells. → Levels of tricarboxylic acid cycle intermediates positively correlate with lifespan. -- Abstract: Many of the genes involved in aging have been identified in organisms ranging from yeast to human. Our previous study showed that deletion of the UGA3 gene-which encodes a zinc-finger transcription factor necessary for γ-aminobutyric acid (GABA)-dependent induction of the UGA1 (GABA aminotransferase), UGA2 (succinate semialdehyde dehydrogenase), and UGA4 (GABA permease) genes-extends replicative lifespan in the budding yeast Saccharomycescerevisiae. Here, we found that deletion of UGA1 lengthened the lifespan, as did deletion of UGA3; in contrast, strains with UGA2 or UGA4 deletions exhibited no lifespan extension. The Δuga1 strain cannot deaminate GABA to succinate semialdehyde. Deletion of GAD1, which encodes the glutamate decarboxylase that converts glutamate into GABA, also increased lifespan. Therefore, two genes in the GABA metabolism pathway, UGA1 and GAD1, were identified as aging genes. Unexpectedly, intracellular GABA levels in mutant cells (except for Δuga2 cells) did not differ from those in wild-type cells. Addition of GABA to culture media, which induces transcription of the UGA structural genes, had no effect on replicative lifespan of wild-type cells. Multivariate analysis of 1 H nuclear magnetic resonance spectra for the whole-cell metabolite levels demonstrated a separation between long-lived and normal-lived strains. Gas chromatography-mass spectrometry analysis of identified metabolites showed that levels of tricarboxylic acid cycle intermediates positively correlated with lifespan extension. These results strongly suggest

  8. Carbon dioxide sensing modulates lifespan and physiology in Drosophila.

    Directory of Open Access Journals (Sweden)

    Peter C Poon

    Full Text Available For nearly all life forms, perceptual systems provide access to a host of environmental cues, including the availability of food and mates as well as the presence of disease and predators. Presumably, individuals use this information to assess the current and future states of the environment and to enact appropriate developmental, behavioral, and regulatory decisions. Recent work using the nematode worm, Caenorhabditis elegans, and the fruit fly, Drosophila melanogaster, has established that aging is subject to modulation through neurosensory systems and that this regulation is evolutionarily conserved. To date, sensory manipulations shown to impact Drosophila aging have involved general loss of function or manipulation of complex stimuli. We therefore know little about the specific inputs, sensors, or associated neural circuits that affect these life and death decisions. We find that a specialized population of olfactory neurons that express receptor Gr63a (a component of the olfactory receptor for gaseous phase CO(2 affects fly lifespan and physiology. Gr63a loss of function leads to extended lifespan, increased fat deposition, and enhanced resistance to some (but not all environmental stresses. Furthermore, we find that the reduced lifespan that accompanies exposure to odors from live yeast is dependent on Gr63a. Together these data implicate a specific sensory cue (CO(2 and its associated receptor as having the ability to modulate fly lifespan and alter organism stress response and physiology. Because Gr63a is expressed in a well-defined population of neurons, future work may now be directed at dissecting more complex neurosensory and neuroendocrine circuits that modulate aging in Drosophila.

  9. Carbon dioxide sensing modulates lifespan and physiology in Drosophila.

    Science.gov (United States)

    Poon, Peter C; Kuo, Tsung-Han; Linford, Nancy J; Roman, Gregg; Pletcher, Scott D

    2010-04-20

    For nearly all life forms, perceptual systems provide access to a host of environmental cues, including the availability of food and mates as well as the presence of disease and predators. Presumably, individuals use this information to assess the current and future states of the environment and to enact appropriate developmental, behavioral, and regulatory decisions. Recent work using the nematode worm, Caenorhabditis elegans, and the fruit fly, Drosophila melanogaster, has established that aging is subject to modulation through neurosensory systems and that this regulation is evolutionarily conserved. To date, sensory manipulations shown to impact Drosophila aging have involved general loss of function or manipulation of complex stimuli. We therefore know little about the specific inputs, sensors, or associated neural circuits that affect these life and death decisions. We find that a specialized population of olfactory neurons that express receptor Gr63a (a component of the olfactory receptor for gaseous phase CO(2)) affects fly lifespan and physiology. Gr63a loss of function leads to extended lifespan, increased fat deposition, and enhanced resistance to some (but not all) environmental stresses. Furthermore, we find that the reduced lifespan that accompanies exposure to odors from live yeast is dependent on Gr63a. Together these data implicate a specific sensory cue (CO(2)) and its associated receptor as having the ability to modulate fly lifespan and alter organism stress response and physiology. Because Gr63a is expressed in a well-defined population of neurons, future work may now be directed at dissecting more complex neurosensory and neuroendocrine circuits that modulate aging in Drosophila.

  10. Landfill Lifespan Estimation: A Case Study

    African Journals Online (AJOL)

    Michael

    2017-12-02

    Dec 2, 2017 ... site selection, design, construction, operation and management. For this reason, it ... This research used the future value of money equation to estimate the lifespan of the ..... Geomatic Engineering, UMaT, Tarkwa, Ghana, pp.

  11. COCOA (Theobroma cacao) Polyphenol-Rich Extract Increases the Chronological Lifespan of Saccharomyces cerevisiae.

    Science.gov (United States)

    Baiges, I; Arola, L

    2016-01-01

    BACKGROUND: Saccharomyces cerevisiae is a model organism with conserved aging pathways. Yeast chronological lifespan experiments mimic the processes involved in human non-dividing tissues, such as the nervous system or skeletal muscle, and can speed up the search for biomolecules with potential anti-aging effects before proceeding to animal studies. OBJECTIVE: To test the effectiveness of a cocoa polyphenol-rich extract (CPE) in expanding the S. cerevisiae chronological lifespan in two conditions: in the stationary phase reached after glucose depletion and under severe caloric restriction. MEASUREMENTS: Using a high-throughput method, wild-type S. cerevisiae and its mitochondrial manganese-dependent superoxide dismutase null mutant (sod2Δ) were cultured in synthetic complete dextrose medium. After 2 days, 0, 5 and 20 mg/ml of CPE were added, and viability was measured throughout the stationary phase. The effects of the major components of CPE were also evaluated. To determine yeast lifespan under severe caloric restriction conditions, cultures were washed with water 24 h after the addition of 0 and 20 mg/ml of CPE, and viability was followed over time. RESULTS : CPE increased the chronological lifespan of S. cerevisiae during the stationary phase in a dose-dependent manner. A similar increase was also observed in (sod2Δ). None of the major CPE components (theobromine, caffeine, maltodextrin, (-)-epicatechin, (+)-catechin and procyanidin B2) was able to increase the yeast lifespan. CPE further increased the yeast lifespan under severe caloric restriction. CONCLUSION: CPE increases the chronological lifespan of S. cerevisiae through a SOD2-independent mechanism. The extract also extends yeast lifespan under severe caloric restriction conditions. The high-throughput assay used makes it possible to simply and rapidly test the efficacy of a large number of compounds on yeast aging, requiring only small amounts, and is thus a convenient screening assay to accelerate

  12. Lifespan extension without fertility reduction following dietary addition of the autophagy activator Torin1 in Drosophila melanogaster.

    Science.gov (United States)

    Mason, Janet S; Wileman, Tom; Chapman, Tracey

    2018-01-01

    Autophagy is a highly conserved mechanism for cellular repair that becomes progressively down-regulated during normal ageing. Hence, manipulations that activate autophagy could increase lifespan. Previous reports show that manipulations to the autophagy pathway can result in longevity extension in yeast, flies, worms and mammals. Under standard nutrition, autophagy is inhibited by the nutrient sensing kinase Target of Rapamycin (TOR). Therefore, manipulations of TOR that increase autophagy may offer a mechanism for extending lifespan. Ideally, such manipulations should be specific and minimise off-target effects, and it is important to discover additional methods for 'clean' lifespan manipulation. Here we report an initial study into the effect of up-regulating autophagy on lifespan and fertility in Drosophila melanogaster by dietary addition of Torin1. Activation of autophagy using this selective TOR inhibitor was associated with significantly increased lifespan in both sexes. Torin1 induced a dose-dependent increase in lifespan in once-mated females. There was no evidence of a trade-off between longevity and fecundity or fertility. Torin1-fed females exhibited significantly elevated fecundity, but also elevated egg infertility, resulting in no net change in overall fertility. This supports the idea that lifespan can be extended without trade-offs in fertility and suggest that Torin1 may be a useful tool with which to pursue anti-ageing research.

  13. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae.

    Science.gov (United States)

    Anderson, Rozalyn M; Bitterman, Kevin J; Wood, Jason G; Medvedik, Oliver; Sinclair, David A

    2003-05-08

    Calorie restriction extends lifespan in a broad range of organisms, from yeasts to mammals. Numerous hypotheses have been proposed to explain this phenomenon, including decreased oxidative damage and altered energy metabolism. In Saccharomyces cerevisiae, lifespan extension by calorie restriction requires the NAD+-dependent histone deacetylase, Sir2 (ref. 1). We have recently shown that Sir2 and its closest human homologue SIRT1, a p53 deacetylase, are strongly inhibited by the vitamin B3 precursor nicotinamide. Here we show that increased expression of PNC1 (pyrazinamidase/nicotinamidase 1), which encodes an enzyme that deaminates nicotinamide, is both necessary and sufficient for lifespan extension by calorie restriction and low-intensity stress. We also identify PNC1 as a longevity gene that is responsive to all stimuli that extend lifespan. We provide evidence that nicotinamide depletion is sufficient to activate Sir2 and that this is the mechanism by which PNC1 regulates longevity. We conclude that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to a low-intensity stress and speculate that nicotinamide might regulate critical cellular processes in higher organisms.

  14. On the genetic mechanisms of nutrient-dependent lifespan and reproduction

    NARCIS (Netherlands)

    Zandveld, Jelle

    2017-01-01

    Dietary restriction (DR), a moderate reduction in nutrient intake, improves health or extends lifespan across many species. Moreover, recent insights have shown that also the effects of specific nutrients are of importance for the beneficial effects of DR rather than intake alone. However, we

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

    Science.gov (United States)

    Chua, Joey

    2014-01-01

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

  16. Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models.

    Science.gov (United States)

    Berryman, Darlene E; Christiansen, Jens Sandahl; Johannsson, Gudmundur; Thorner, Michael O; Kopchick, John J

    2008-12-01

    Animal models are fundamentally important in our quest to understand the genetic, epigenetic, and environmental factors that contribute to human aging. In comparison to humans, relatively short-lived mammals are useful models as they allow for rapid assessment of both genetic manipulation and environmental intervention as related to longevity. These models also allow for the study of clinically relevant pathologies as a function of aging. Data associated with more distant species offers additional insight and critical consideration of the basic physiological processes and molecular mechanisms that influence lifespan. Consistently, two interventions, caloric restriction and repression of the growth hormone (GH)/insulin-like growth factor-1/insulin axis, have been shown to increase lifespan in both invertebrates and vertebrate animal model systems. Caloric restriction (CR) is a nutrition intervention that robustly extends lifespan whether it is started early or later in life. Likewise, genes involved in the GH/IGF-1 signaling pathways can lengthen lifespan in vertebrates and invertebrates, implying evolutionary conservation of the molecular mechanisms. Specifically, insulin and insulin-like growth factor-1 (IGF-1)-like signaling and its downstream intracellular signaling molecules have been shown to be associated with lifespan in fruit flies and nematodes. More recently, mammalian models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended lifespans as compared to control siblings. Importantly, this research has also shown that these genetic alterations can keep the animals healthy and disease-free for longer periods and can alleviate specific age-related pathologies similar to what is observed for CR individuals. Thus, these mutations may not only extend lifespan but may also improve healthspan, the general health and quality of life of an organism as it ages. In this review, we will provide an overview of how the

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

    Science.gov (United States)

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

    2017-09-01

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

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

    International Nuclear Information System (INIS)

    Fierro-Gonzalez, Juan Carlos; Gonzalez-Barrios, Maria; Miranda-Vizuete, Antonio; Swoboda, Peter

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-03-18

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

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

    OpenAIRE

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

    2015-01-01

    This study extends Uses and Gratifications theory by examining the uses and gratifications of a new technological device, the tablet computer, and investigating the differential uses and gratifications of tablet computers across the life-span. First, we utilized a six-week tablet training intervention to adapt and extend existing measures to the tablet as a technological device. Next, we used paper-based and online surveys (N=847), we confirmed four main uses of tablets: 1) Information Seekin...

  1. Trade-off between reproduction and lifespan of the rotifer Brachionus plicatilis under different food conditions.

    Science.gov (United States)

    Sun, Yunfei; Hou, Xinying; Xue, Xiaofeng; Zhang, Lu; Zhu, Xuexia; Huang, Yuan; Chen, Yafen; Yang, Zhou

    2017-11-13

    Phaeocystis globosa, one of the most typical red tide-forming species, is usually mixed in the food composition of rotifers. To explore how rotifers respond by adjusting life history strategy when feeding on different quality foods, we exposed the rotifer Brachionus plicatilis to cultures with 100% Chlorella, a mixture of 50% P. globosa and 50% Chlorella, or 100% P. globosa. Results showed that rotifers exposed to 100% Chlorella or to mixed diets produced more total offspring and had higher age-specific fecundity than those exposed to 100% P. globosa. Food combination significantly affected the net reproduction rates of rotifers. By contrast, rotifers that fed on 100% P. globosa or on mixed diets had a longer lifespan than those fed on 100% Chlorella. The overall performances (combining reproduction and lifespan together) of rotifers cultured in 100% Chlorella or mixed diets were significantly higher than those cultured in 100% P. globosa. In general, Chlorella favors rotifers reproduction at the cost of shorter lifespan, whereas P. globosa tends to extend the lifespan of rotifers with lower fecundity, indicating that trade-off exists between reproduction and lifespan under different food conditions. The present study also suggests that rotifers may have the potential to control harmful P. globosa.

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

    Science.gov (United States)

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

    2015-06-01

    Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  3. Extension of Drosophila lifespan by Rhodiola rosea through a mechanism independent from dietary restriction.

    Directory of Open Access Journals (Sweden)

    Samuel E Schriner

    Full Text Available Rhodiola rosea has been extensively used to improve physical and mental performance and to protect against stress. We, and others, have reported that R. rosea can extend lifespan in flies, worms, and yeast. However, its molecular mechanism is currently unknown. Here, we tested whether R. rosea might act through a pathway related to dietary restriction (DR that can extend lifespan in a range of model organisms. While the mechanism of DR itself is also unknown, three molecular pathways have been associated with it: the silent information regulator 2 (SIR2 proteins, insulin and insulin-like growth factor signaling (IIS, and the target of rapamycin (TOR. In flies, DR is implemented through a reduction in dietary yeast content. We found that R. rosea extract extended lifespan in both sexes independent of the yeast content in the diet. We also found that the extract extended lifespan when the SIR2, IIS, or TOR pathways were genetically perturbed. Upon examination of water and fat content, we found that R. rosea decreased water content and elevated fat content in both sexes, but did not sensitize flies to desiccation or protect them against starvation. There were some sex-specific differences in response to R. rosea. In female flies, the expression levels of glycolytic genes and dSir2 were down-regulated, and NADH levels were decreased. In males however, R. rosea provided no protection against heat stress and had no effect on the major heat shock protein HSP70 and actually down-regulated the mitochondrial HSP22. Our findings largely rule out an elevated general resistance to stress and DR-related pathways as mechanistic candidates. The latter conclusion is especially relevant given the limited potential for DR to improve human health and lifespan, and presents R. rosea as a potential viable candidate to treat aging and age-related diseases in humans.

  4. MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Oliver Medvedik

    2007-10-01

    Full Text Available Calorie restriction (CR robustly extends the lifespan of numerous species. In the yeast Saccharomyces cerevisiae, CR has been proposed to extend lifespan by boosting the activity of sirtuin deacetylases, thereby suppressing the formation of toxic repetitive ribosomal DNA (rDNA circles. An alternative theory is that CR works by suppressing the TOR (target of rapamycin signaling pathway, which extends lifespan via mechanisms that are unknown but thought to be independent of sirtuins. Here we show that TOR inhibition extends lifespan by the same mechanism as CR: by increasing Sir2p activity and stabilizing the rDNA locus. Further, we show that rDNA stabilization and lifespan extension by both CR and TOR signaling is due to the relocalization of the transcription factors Msn2p and Msn4p from the cytoplasm to the nucleus, where they increase expression of the nicotinamidase gene PNC1. These findings suggest that TOR and sirtuins may be part of the same longevity pathway in higher organisms, and that they may promote genomic stability during aging.

  5. A transcription elongation factor that links signals from the reproductive system to lifespan extension in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Arjumand Ghazi

    2009-09-01

    Full Text Available In Caenorhabditis elegans and Drosophila melanogaster, the aging of the soma is influenced by the germline. When germline-stem cells are removed, aging slows and lifespan is increased. The mechanism by which somatic tissues respond to loss of the germline is not well-understood. Surprisingly, we have found that a predicted transcription elongation factor, TCER-1, plays a key role in this process. TCER-1 is required for loss of the germ cells to increase C. elegans' lifespan, and it acts as a regulatory switch in the pathway. When the germ cells are removed, the levels of TCER-1 rise in somatic tissues. This increase is sufficient to trigger key downstream events, as overexpression of tcer-1 extends the lifespan of normal animals that have an intact reproductive system. Our findings suggest that TCER-1 extends lifespan by promoting the expression of a set of genes regulated by the conserved, life-extending transcription factor DAF-16/FOXO. Interestingly, TCER-1 is not required for DAF-16/FOXO to extend lifespan in animals with reduced insulin/IGF-1 signaling. Thus, TCER-1 specifically links the activity of a broadly deployed transcription factor, DAF-16/FOXO, to longevity signals from reproductive tissues.

  6. Repeated intra-specific divergence in lifespan and ageing of African annual fishes along an aridity gradient

    DEFF Research Database (Denmark)

    Blažek, Radim; Polačik, Matej; Kačer, Petr

    2017-01-01

    intrinsic lifespans and a greater increase in mortality with age, more pronounced cellular and physiological deterioration (oxidative damage, tumor load), and a faster decline in fertility than populations from wetter regions. This parallel intra-specific divergence in lifespan and ageing was not associated......Lifespan and ageing are substantially modified by natural selection. Across species, higher extrinsic (environmentally-related) mortality (and hence shorter life expectancy) selects for the evolution of more rapid ageing. However, among populations within species, high extrinsic mortality can lead...... to extended lifespan and slower ageing as a consequence of condition-dependent survival. Using within-species contrasts of eight natural populations of Nothobranchius fishes in common garden experiments, we demonstrate that populations originating from dry regions (with short life expectancy) had shorter...

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

    Science.gov (United States)

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

    2009-12-23

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

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

    Science.gov (United States)

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

    2015-12-01

    The present study supports and extends previous research on the developmental differences in women's dreams across the lifespan. The participants included 75 Canadian women in each of 5 age groups from adolescence to old age including 12-17, 18-24, 25-39, 40-64, and 65-85, totaling 375 women. One dream per participant was scored by two independent judges using the method of content analysis. Trend analysis was used to determine the ontogenetic pattern of the dream content categories. Results demonstrated significant ontogenetic decreases (linear trends) for female and familiar characters, activities, aggression, and friendliness. These patterns of dream imagery reflect the waking developmental patterns as proposed by social theories and recognized features of aging as postulated by the continuity hypothesis. Limitations and suggestions for future research including the examining of developmental patterns in the dreams of males are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Social consequences of Garona NPP lifespan extension issue

    International Nuclear Information System (INIS)

    Millan, Miguel A.

    2010-01-01

    On June 3, Spanish Nuclear Safety regulatory body, CSN, declared unanimously 'Santa Maria de Garona' nuclear power plant, a BWR reactor, as entirely compliant with all the safety requirements to extend its operation for the 2009-2019 period. Nevertheless, on July 3, Spanish government allowed Garona Nuclear Power Plant for 4 years more, two years more than the design life, 40 years. From June 3 until July 3 there were several public demonstrations in support of Garona continuity. Every day a lot of debates, interviews and articles, regarding Garona issue took place in TV channels, radio stations and newspapers. This paper shows all the activities that the owner, workers, unions and non-profit associations carried out to show the good state of the facility, also includes a discussion regarding the data showed by the government to shut-down the facility eight years before lifespan. And finally, what to do in those cases is discussed in this paper. (authors)

  10. Sex differences and stress across the lifespan

    Science.gov (United States)

    Bale, Tracy L; Epperson, C Neill

    2015-01-01

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

  11. Sex differences and stress across the lifespan.

    Science.gov (United States)

    Bale, Tracy L; Epperson, C Neill

    2015-10-01

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

  12. Age-Dependence and Aging-Dependence: Neuronal Loss and Lifespan in a C. elegans Model of Parkinson's Disease.

    Science.gov (United States)

    Apfeld, Javier; Fontana, Walter

    2017-12-23

    It is often assumed, but not established, that the major neurodegenerative diseases, such as Parkinson's disease, are not just age-dependent (their incidence changes with time) but actually aging-dependent (their incidence is coupled to the process that determines lifespan). To determine a dependence on the aging process requires the joint probability distribution of disease onset and lifespan. For human Parkinson's disease, such a joint distribution is not available, because the disease cuts lifespan short. To acquire a joint distribution, we resorted to an established C. elegans model of Parkinson's disease in which the loss of dopaminergic neurons is not fatal. We find that lifespan is not correlated with the loss of individual neurons. Therefore, neuronal loss is age-dependent and aging-independent. We also find that a lifespan-extending intervention into insulin/IGF1 signaling accelerates the loss of specific dopaminergic neurons, while leaving death and neuronal loss times uncorrelated. This suggests that distinct and compartmentalized instances of the same genetically encoded insulin/IGF1 signaling machinery act independently to control neurodegeneration and lifespan in C. elegans . Although the human context might well be different, our study calls attention to the need to maintain a rigorous distinction between age-dependence and aging-dependence.

  13. QUANTIFYING LIFE STYLE IMPACT ON LIFESPAN

    Directory of Open Access Journals (Sweden)

    Antonello Lorenzini

    2012-12-01

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

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

    Directory of Open Access Journals (Sweden)

    David E Shore

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

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

    Science.gov (United States)

    Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

    2015-12-25

    Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Intestinal IRE1 Is Required for Increased Triglyceride Metabolism and Longer Lifespan under Dietary Restriction.

    Science.gov (United States)

    Luis, Nuno Miguel; Wang, Lifen; Ortega, Mauricio; Deng, Hansong; Katewa, Subhash D; Li, Patrick Wai-Lun; Karpac, Jason; Jasper, Heinrich; Kapahi, Pankaj

    2016-10-25

    Dietary restriction (DR) is one of the most robust lifespan-extending interventions in animals. The beneficial effects of DR involve a metabolic adaptation toward increased triglyceride usage. The regulatory mechanism and the tissue specificity of this metabolic switch remain unclear. Here, we show that the IRE1/XBP1 endoplasmic reticulum (ER) stress signaling module mediates metabolic adaptation upon DR in flies by promoting triglyceride synthesis and accumulation in enterocytes (ECs) of the Drosophila midgut. Consistently, IRE1/XBP1 function in ECs is required for increased longevity upon DR. We further identify sugarbabe, a Gli-like zinc-finger transcription factor, as a key mediator of the IRE1/XBP1-regulated induction of de novo lipogenesis in ECs. Overexpression of sugarbabe rescues metabolic and lifespan phenotypes of IRE1 loss-of-function conditions. Our study highlights the critical role of metabolic adaptation of the intestinal epithelium for DR-induced lifespan extension and explores the IRE1/XBP1 signaling pathway regulating this adaptation and influencing lifespan. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Neurodevelopmental origins of lifespan changes in brain and cognition

    Science.gov (United States)

    Walhovd, Kristine B.; Krogsrud, Stine K.; Bartsch, Hauke; Bjørnerud, Atle; Due-Tønnessen, Paulina; Grydeland, Håkon; Hagler, Donald J.; Håberg, Asta K.; Kremen, William S.; Ferschmann, Lia; Nyberg, Lars; Panizzon, Matthew S.; Rohani, Darius A.; Skranes, Jon; Storsve, Andreas B.; Sølsnes, Anne Elisabeth; Tamnes, Christian K.; Thompson, Wesley K.; Reuter, Chase; Dale, Anders M.; Fjell, Anders M.

    2016-01-01

    Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4–88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother–Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain–cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course. PMID:27432992

  18. Proliferative lifespan is conserved after nuclear transfer.

    Science.gov (United States)

    Clark, A John; Ferrier, Patricia; Aslam, Samena; Burl, Sarah; Denning, Chris; Wylie, Diana; Ross, Arlene; de Sousa, Paul; Wilmut, Ian; Cui, Wei

    2003-06-01

    Cultured primary cells exhibit a finite proliferative lifespan, termed the Hayflick limit. Cloning by nuclear transfer can reverse this cellular ageing process and can be accomplished with cultured cells nearing senescence. Here we describe nuclear transfer experiments in which donor cell lines at different ages and with different proliferative capacities were used to clone foetuses and animals from which new primary cell lines were generated. The rederived lines had the same proliferative capacity and rate of telomere shortening as the donor cell lines, suggesting that these are innate, genetically determined, properties that are conserved by nuclear transfer.

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

    Directory of Open Access Journals (Sweden)

    Mai-Britt Mosbech

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

  20. Advances in asthma 2015: Across the lifespan.

    Science.gov (United States)

    Liu, Andrew H; Anderson, William C; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J

    2016-08-01

    In 2015, progress in understanding asthma ranged from insights to asthma inception, exacerbations, and severity to advancements that will improve disease management throughout the lifespan. 2015's insights to asthma inception included how the intestinal microbiome affects asthma expression with the identification of specific gastrointestinal bacterial taxa in early infancy associated with less asthma risk, possibly by promoting regulatory immune development at a critical early age. The relevance of epigenetic mechanisms in regulating asthma-related gene expression was strengthened. Predicting and preventing exacerbations throughout life might help to reduce progressive lung function decrease and disease severity in adulthood. Although allergy has long been linked to asthma exacerbations, a mechanism through which IgE impairs rhinovirus immunity and underlies asthma exacerbations was demonstrated and improved by anti-IgE therapy (omalizumab). Other key molecular pathways underlying asthma exacerbations, such as cadherin-related family member 3 (CDHR3) and orosomucoid like 3 (ORMDL3), were elucidated. New anti-IL-5 therapeutics, mepolizumab and reslizumab, were US Food and Drug Administration approved for the treatment of patients with severe eosinophilic asthma. In a clinical trial the novel therapeutic inhaled GATA3 mRNA-specific DNAzyme attenuated early- and late-phase allergic responses to inhaled allergen. These current findings are significant steps toward addressing unmet needs in asthma prevention, severity modification, disparities, and lifespan outcomes. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Male lifespan and the secondary sex ratio.

    Science.gov (United States)

    Catalano, Ralph; Bruckner, Tim

    2006-01-01

    Literature speculating on the fetal origins of later life morbidity often invokes the "damaged cohort" theory, i.e., that maternal responses to exogenous shocks induce "stress reactivity" in fetuses and thereby shorten the lifespan of males in utero during stressful times. A rival, or "culled cohort," theory posits that exogenous shocks to gravid females induce spontaneous abortions of frail male fetuses, leaving relatively hardy survivors who enjoy, on average, lifespans longer than males in less stressed birth cohorts. A recent test based on archival data from Sweden supported the culled cohort theory. Several characteristics of the Swedish data, however, raise questions regarding the external validity of the findings. We repeat the test with data from Denmark, Iceland, and England and Wales. We use time-series methods that control for trends, seasonal cycles, and other forms of autocorrelation that could confound the test. None of the results supports the "damaged cohort" theory. Consistent with the Swedish findings and with evolutionary theory, we find support in Iceland and England and Wales for the "culled cohort" theory. We discuss the implications of our findings for basic research as well as for public health.

  2. A Novel Physiology-Based Mathematical Model to Estimate Red Blood Cell Lifespan in Different Human Age Groups.

    Science.gov (United States)

    An, Guohua; Widness, John A; Mock, Donald M; Veng-Pedersen, Peter

    2016-09-01

    Direct measurement of red blood cell (RBC) survival in humans has improved from the original accurate but limited differential agglutination technique to the current reliable, safe, and accurate biotin method. Despite this, all of these methods are time consuming and require blood sampling over several months to determine the RBC lifespan. For situations in which RBC survival information must be obtained quickly, these methods are not suitable. With the exception of adults and infants, RBC survival has not been extensively investigated in other age groups. To address this need, we developed a novel, physiology-based mathematical model that quickly estimates RBC lifespan in healthy individuals at any age. The model is based on the assumption that the total number of RBC recirculations during the lifespan of each RBC (denoted by N max) is relatively constant for all age groups. The model was initially validated using the data from our prior infant and adult biotin-labeled red blood cell studies and then extended to the other age groups. The model generated the following estimated RBC lifespans in 2-year-old, 5-year-old, 8-year-old, and 10-year-old children: 62, 74, 82, and 86 days, respectively. We speculate that this model has useful clinical applications. For example, HbA1c testing is not reliable in identifying children with diabetes because HbA1c is directly affected by RBC lifespan. Because our model can estimate RBC lifespan in children at any age, corrections to HbA1c values based on the model-generated RBC lifespan could improve diabetes diagnosis as well as therapy in children.

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

    Science.gov (United States)

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

    2015-01-01

    This study extends Uses and Gratifications theory by examining the uses and gratifications of a new technological device, the tablet computer, and investigating the differential uses and gratifications of tablet computers across the life-span. First, we utilized a six-week tablet training intervention to adapt and extend existing measures to the tablet as a technological device. Next, we used paper-based and online surveys (N=847), we confirmed four main uses of tablets: 1) Information Seeking, 2) Relationship Maintenance, 3) Style, 4) Amusement and Killing time, and added one additional use category 5) Organization. We discovered differences among the five main uses of tablets across the life-span, with older adults using tablets the least overall. Builders, Boomers, GenX and GenY all reported the highest means for information seeking. Finally, we used a structural equation model to examine how uses and gratifications predicts hours of tablet use. The study provides limitations and suggestions for future research and marketers. In particular, this study offers insight to the relevancy of theory as it applies to particular information and communication technologies and consideration of how different periods in the life-span affect tablet motivations. PMID:26113769

  4. Caloric Restriction-Induced Extension of Chronological Lifespan Requires Intact Respiration in Budding Yeast.

    Science.gov (United States)

    Kwon, Young-Yon; Lee, Sung-Keun; Lee, Cheol-Koo

    2017-04-01

    Caloric restriction (CR) has been shown to extend lifespan and prevent cellular senescence in various species ranging from yeast to humans. Many effects of CR may contribute to extend lifespan. Specifically, CR prevents oxidative damage from reactive oxygen species (ROS) by enhancing mitochondrial function. In this study, we characterized 33 single electron transport chain (ETC) gene-deletion strains to identify CR-induced chronological lifespan (CLS) extension mechanisms. Interestingly, defects in 17 of these 33 ETC gene-deleted strains showed loss of both respiratory function and CR-induced CLS extension. On the contrary, the other 16 respiration-capable mutants showed increased CLS upon CR along with increased mitochondrial membrane potential (MMP) and intracellular adenosine triphosphate (ATP) levels, with decreased mitochondrial superoxide generation. We measured the same parameters in the 17 non-respiratory mutants upon CR. CR simultaneously increased MMP and mitochondrial superoxide generation without altering intracellular ATP levels. In conclusion, respiration is essential for CLS extension by CR and is important for balancing MMP, ROS, and ATP levels.

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

    Science.gov (United States)

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

    2015-11-01

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

  6. Injuries can prolong lifespan in Drosophila melanogaster males

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  7. A Motivational Theory of Life-Span Development

    Science.gov (United States)

    Heckhausen, Jutta; Wrosch, Carsten; Schulz, Richard

    2010-01-01

    This article had four goals. First, the authors identified a set of general challenges and questions that a life-span theory of development should address. Second, they presented a comprehensive account of their Motivational Theory of Life-Span Development. They integrated the model of optimization in primary and secondary control and the…

  8. Minority Stress across the Career-Lifespan Trajectory

    Science.gov (United States)

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

    2016-01-01

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

  9. The Path to Competence: A Lifespan Developmental Perspective on Reading

    Science.gov (United States)

    Alexander, Patricia A.

    2012-01-01

    The purpose of this document is to present a developmental model of reading that encompasses changes across the lifespan. The need for such a lifespan orientation toward reading within our educational institutions is great. Until we adopt this lifelong perspective, we continue to run the risk of turning out undeveloped, unmotivated, and uncritical…

  10. [Combined hormonal contraception in cycles artificially extended].

    Science.gov (United States)

    Bustillos-Alamilla, Edgardo; Zepeda-Zaragoza, J; Hernández-Ruiz, M A; Briones-Landa, Carlos Humberto

    2010-01-01

    To compare the bleeding patterns, satisfaction and tolerability of 3 different contraceptive in an extended regimens in the service of Family Planning of the North Central Hospital of PEMEX. Healthy, adult women with desire of contraception for one year (N 120) were randomly assigned to receive oral contraceptive drospirenone/ethinyl E2 (group1), the norelgestromin/ethinyl E2 transdermal patch (group 2) and vaginal ring etonogestrel/ ethinyl E2 (group 3) in an extended regimen (42 consecutive days, 1 hormone-free week). Study assessments were conducted at scheduled visits at the time of initial screening, at baseline after 1, 3, 6, and 12 months. Subjects recorded menstrual associated symptoms bleeding data and completed satisfaction questionnaires. Subjects and investigators provided overall assessments of the regimens. Extended use of 3 different contraceptive resulted in fewer bleeding days in every group (66.6%, 55% and 58.3% P 0.0024), and less mastalgia and menstrual pain. Subjects were highly satisfied with three regimens (93.3%, 96.6% and 91.6% P 0.00421). Although not mayor adverse events were reported with this regimen, there was an increase in spotting days; it decreased with each successive cycle of therapy. Efficacy and safety were similar to those reported for traditional cycle. Extended-contraceptive regimen delays menses and reduces bleeding, a profile that may be preferred by women who seek flexibility with their contraceptive method.

  11. Lifespan extension and the doctrine of double effect.

    Science.gov (United States)

    Capitaine, Laura; Devolder, Katrien; Pennings, Guido

    2013-06-01

    Recent developments in biogerontology--the study of the biology of ageing--suggest that it may eventually be possible to intervene in the human ageing process. This, in turn, offers the prospect of significantly postponing the onset of age-related diseases. The biogerontological project, however, has met with strong resistance, especially by deontologists. They consider the act of intervening in the ageing process impermissible on the grounds that it would (most probably) bring about an extended maximum lifespan--a state of affairs that they deem intrinsically bad. In a bid to convince their deontological opponents of the permissibility of this act, proponents of biogerontology invoke an argument which is grounded in the doctrine of double effect. Surprisingly, their argument, which we refer to as the 'double effect argument', has gone unnoticed. This article exposes and critically evaluates this 'double effect argument'. To this end, we first review a series of excerpts from the ethical debate on biogerontology in order to substantiate the presence of double effect reasoning. Next, we attempt to determine the role that the 'double effect argument' is meant to fulfil within this debate. Finally, we assess whether the act of intervening in ageing actually can be justified using double effect reasoning.

  12. Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice.

    Science.gov (United States)

    Mitchell, Sarah J; Bernier, Michel; Aon, Miguel A; Cortassa, Sonia; Kim, Eun Young; Fang, Evandro F; Palacios, Hector H; Ali, Ahmed; Navas-Enamorado, Ignacio; Di Francesco, Andrea; Kaiser, Tamzin A; Waltz, Tyler B; Zhang, Ning; Ellis, James L; Elliott, Peter J; Frederick, David W; Bohr, Vilhelm A; Schmidt, Mark S; Brenner, Charles; Sinclair, David A; Sauve, Anthony A; Baur, Joseph A; de Cabo, Rafael

    2018-03-06

    The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD + , is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways. Targeted NAD metabolome analysis in liver revealed depressed expression of NAM salvage in NAM-treated mice, an effect counteracted by higher expression of de novo NAD biosynthetic enzymes. Although neither hepatic NAD + nor NADP + was boosted by NAM, acetylation of some SIRT1 targets was enhanced by NAM supplementation in a diet- and NAM dose-dependent manner. Collectively, our results show health improvement in NAM-supplemented HFD-fed mice in the absence of survival effects. Published by Elsevier Inc.

  13. Short-Term, Intermittent Fasting Induces Long-Lasting Gut Health and TOR-Independent Lifespan Extension.

    Science.gov (United States)

    Catterson, James H; Khericha, Mobina; Dyson, Miranda C; Vincent, Alec J; Callard, Rebecca; Haveron, Steven M; Rajasingam, Arjunan; Ahmad, Mumtaz; Partridge, Linda

    2018-06-04

    Intermittent fasting (IF) can improve function and health during aging in laboratory model organisms, but the mechanisms at work await elucidation. We subjected fruit flies (Drosophila melanogaster) to varying degrees of IF and found that just one month of a 2-day fed:5-day fasted IF regime at the beginning of adulthood was sufficient to extend lifespan. This long-lasting, beneficial effect of early IF was not due to reduced fecundity. Starvation resistance and resistance to oxidative and xenobiotic stress were increased after IF. Early-life IF also led to higher lipid content in 60-day-old flies, a potential explanation for increased longevity. Guts of flies 40 days post-IF showed a significant reduction in age-related pathologies and improved gut barrier function. Improved gut health was also associated with reduced relative bacterial abundance. Early IF thus induced profound long-term changes. Pharmacological and genetic epistasis analysis showed that IF acted independently of the TOR pathway because rapamycin and IF acted additively to extend lifespan, and global expression of a constitutively active S6K did not attenuate the IF-induced lifespan extension. We conclude that short-term IF during early life can induce long-lasting beneficial effects, with robust increase in lifespan in a TOR-independent manner, probably at least in part by preserving gut health. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. 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.

  15. 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.

  16. Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs.

    Directory of Open Access Journals (Sweden)

    Susan Broughton

    Full Text Available The insulin/IGF-like signalling (IIS pathway has diverse functions in all multicellular organisms, including determination of lifespan. The seven insulin-like peptides (DILPs in Drosophila are expressed in a stage- and tissue-specific manner. Partial ablation of the median neurosecretory cells (mNSCs in the brain, which produce three DILPs, extends lifespan, reduces fecundity, alters lipid and carbohydrate metabolism and increases oxidative stress resistance. To determine if reduced expression of DILPs is causal in these effects, and to investigate possible functional diversification and redundancy between DILPs, we used RNA interference to lower specifically the transcript and protein levels of dilp2, the most highly expressed of the mNSC-derived DILPs. We found that DILP2 was limiting only for the increased whole-body trehalose content associated with mNSC-ablation. We observed a compensatory increase in dilp3 and 5 mRNA upon dilp2 knock down. By manipulation of dfoxo and dInR, we showed that the increase in dilp3 is regulated via autocrine insulin signaling in the mNSCs. Our study demonstrates that, despite the correlation between reduced dilp2 mRNA levels and lifespan-extension often observed, DILP2 reduction is not sufficient to extend lifespan. Nor is the increased trehalose storage associated with reduced IIS sufficient to extend lifespan. To understand the normal regulation of expression of the dilps and any functional diversification between them will require independent control of the expression of different dilps.

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

    Directory of Open Access Journals (Sweden)

    Gene eAbles

    2014-05-01

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

  18. Bicarbonate-sensitive calcification and lifespan of klotho-deficient mice.

    Science.gov (United States)

    Leibrock, Christina B; Voelkl, Jakob; Kohlhofer, Ursula; Quintanilla-Martinez, Leticia; Kuro-O, Makoto; Lang, Florian

    2016-01-01

    Klotho, a protein counteracting aging, is a powerful inhibitor of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] formation and regulator of mineral metabolism. In klotho hypomorphic (kl/kl) mice, excessive 1,25(OH)2D3 formation leads to hypercalcemia, hyperphosphatemia and vascular calcification, severe growth deficits, accelerated aging and early death. Kl/kl mice further suffer from extracellular volume depletion and hypotension, leading to the stimulation of antidiuretic hormone and aldosterone release. A vitamin D-deficient diet, restriction of dietary phosphate, inhibition of mineralocorticoid receptors with spironolactone, and dietary NaCl all extend the lifespan of kl/kl mice. Kl/kl mice suffer from acidosis. The present study explored whether replacement of tap drinking water by 150 mM NaHCO3 affects the growth, tissue calcification, and lifespan of kl/kl mice. As a result, NaHCO3 administration to kl/kl mice did not reverse the growth deficit but substantially decreased tissue calcification and significantly increased the average lifespan from 78 to 127 days. NaHCO3 did not significantly affect plasma concentrations of 1,25(OH)2D3 and Ca(2+) but significantly decreased plasma phosphate concentration and plasma aldosterone concentration. The present study reveals a novel effect of bicarbonate, i.e., a favorable influence on vascular calcification and early death of klotho-deficient mice. Copyright © 2016 the American Physiological Society.

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

    Directory of Open Access Journals (Sweden)

    Hyun Won Seo

    2015-01-01

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

  20. Calycosin promotes lifespan in Caenorhabditis elegans through insulin signaling pathway via daf-16, age-1 and daf-2.

    Science.gov (United States)

    Lu, Lulu; Zhao, Xuan; Zhang, Jianyong; Li, Miao; Qi, Yonghao; Zhou, Lijun

    2017-07-01

    The naturally occurring calycosin is a known antioxidant that prevents redox imbalance in organisms. However, calycosin's effect on lifespan and its physiological molecular mechanisms are not yet well understood. In this study, we demonstrated that calycosin could prolong the lifespan of Caenorhabditis elegans, and that such extension was associated with its antioxidant capability as well as its ability to enhance stress resistance and reduce ROS (reactive oxygen species) accumulation. To explore mechanisms of this longevity effect, we assessed the impact of calycosin on lifespans of insulin-signaling impaired worms: daf-2, age-1, and daf-16 mutants. We found that calycosin did not alter the lifespan of all three mutants, thereby suggesting that calycosin requires insulin signaling to promote lifespan extension. On the other hand, we observed that calycosin could enhance the nuclear translocation of the core transcription factor DAF-16/FoXO instead of the conserved stress-responsive transcription factor SKN-1/Nrf-2. This observation is consistent with the understanding that the nuclear localized DAF-16 up-regulates its downstream targets sod-3, ctl-1, and hsp-16.2. Lastly, it is also noteworthy that the longevity effect of calycosin is likely not associated with the calorie restriction mechanism. Collectively, our results strongly suggest that calycosin could function as an antioxidant to extend the lifespan of C. elegans by enhancing nucleus translocation of DAF-16 through the insulin-signaling pathway. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. Lifespan extension in the spontaneous dwarf rat and enhanced resistance to hyperoxia-induced mortality.

    Science.gov (United States)

    Sasaki, Toru; Tahara, Shoichi; Shinkai, Tadashi; Kuramoto, Kazunao; Matsumoto, Shigenobu; Yanabe, Makoto; Takagi, Shohei; Kondo, Hiroshi; Kaneko, Takao

    2013-05-01

    Lifespan extension has been demonstrated in dwarfism mouse models relative to their wild-type. The spontaneous dwarf rat (SDR) was isolated from a closed colony of Sprague-Dawley (SD) rats. Growth hormone deficiencies have been indicated to be responsible for dwarfism in SDR. Survival time, the markers of oxidative stress, antioxidant enzymes, and resistance to hyperoxia were compared between SDR and SD rats, to investigate whether SDR, a dwarfism rat model, also extends lifespan and has an enhanced resistance to oxidative stress. SDRs lived 38% longer than SD rats on average. This is the first report to show that dwarf rats exhibit lifespan extensions similar to Ames and Snell mice. Decreased 8-oxo-2'-deoxyguanosine (8-oxodG) content, a marker of oxidative DNA damage, indicated suppressed oxidative stress in the liver, kidney, and lung of SDRs. Increased glutathione peroxidase enzyme activity was consistent with decreased 8-oxodG content in the same tissues. The heart and brain showed a similar tendency, but this was not significant. However, the catalase and superoxide dismutase enzyme activities of SDRs were not different from those of SD rats in any tissue. This was not what the original null hypothesis predicted. SDRs had potent resistance to the toxicity associated with high O2 (85%) exposure. The mean survival time in SDRs was more than 147% that of SD rats with 168h O2 exposure. These results suggest that the enhanced resistance to oxidative stress of SDRs associated with enhanced hydrogen peroxide elimination may support its potential role in lifespan extension. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Extended objects

    International Nuclear Information System (INIS)

    Creutz, M.

    1976-01-01

    After some disconnected comments on the MIT bag and string models for extended hadrons, I review current understanding of extended objects in classical conventional relativistic field theories and their quantum mechanical interpretation

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    and neurodegeneration in A-T patients is unclear. Here we report and examine the significance of increased PARylation, low NAD(+), and mitochondrial dysfunction in ATM-deficient neurons, mice, and worms. Treatments that replenish intracellular NAD(+) reduce the severity of A-T neuropathology, normalize neuromuscular...... function, delay memory loss, and extend lifespan in both animal models. Mechanistically, treatments that increase intracellular NAD(+) also stimulate neuronal DNA repair and improve mitochondrial quality via mitophagy. This work links two major theories on aging, DNA damage accumulation, and mitochondrial...

  4. Docosahexaenoic Acid and Cognition throughout the Lifespan

    Directory of Open Access Journals (Sweden)

    Michael J. Weiser

    2016-02-01

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

  5. Understanding aggressive behaviour across the lifespan.

    Science.gov (United States)

    Liu, J; Lewis, G; Evans, L

    2013-03-01

    Aggressive behaviour is the observable manifestation of aggression and is often associated with developmental transitions and a range of medical and psychiatric diagnoses across the lifespan. As healthcare professionals involved in the medical and psychosocial care of patients from birth through death, nurses frequently encounter - and may serve as - both victims and perpetrators of aggressive behaviour in the workplace. While the nursing literature has continually reported research on prevention and treatment approaches, less emphasis has been given to understanding the aetiology, including contextual precipitants of aggressive behaviour. This paper provides a brief review of the biological, social and environmental risk factors that purportedly give rise to aggressive behaviour. Further, many researchers have focused specifically on aggressive behaviour in adolescence and adulthood. Less attention has been given to understanding the aetiology of such behaviour in young children and older adults. This paper emphasizes the unique risk factors for aggressive behaviour across the developmental spectrum, including childhood, adolescence, adulthood and late life. Appreciation of the risk factors of aggressive behaviour, and, in particular, how they relate to age-specific manifestations, can aid nurses in better design and implementation of prevention and treatment programmes. © 2012 Blackwell Publishing.

  6. Visual Word Recognition Across the Adult Lifespan

    Science.gov (United States)

    Cohen-Shikora, Emily R.; Balota, David A.

    2016-01-01

    The current study examines visual word recognition in a large sample (N = 148) across the adult lifespan and across a large set of stimuli (N = 1187) in three different lexical processing tasks (pronunciation, lexical decision, and animacy judgments). Although the focus of the present study is on the influence of word frequency, a diverse set of other variables are examined as the system ages and acquires more experience with language. Computational models and conceptual theories of visual word recognition and aging make differing predictions for age-related changes in the system. However, these have been difficult to assess because prior studies have produced inconsistent results, possibly due to sample differences, analytic procedures, and/or task-specific processes. The current study confronts these potential differences by using three different tasks, treating age and word variables as continuous, and exploring the influence of individual differences such as vocabulary, vision, and working memory. The primary finding is remarkable stability in the influence of a diverse set of variables on visual word recognition across the adult age spectrum. This pattern is discussed in reference to previous inconsistent findings in the literature and implications for current models of visual word recognition. PMID:27336629

  7. Epigenetic variation during the adult lifespan

    DEFF Research Database (Denmark)

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

    2012-01-01

    The accumulation of epigenetic changes was proposed to contribute to the age-related increase in the risk of most common diseases. In this study on 230 monozygotic twin pairs (MZ pairs), aged 18-89 years, we investigated the occurrence of epigenetic changes over the adult lifespan. Using mass...... individuals, ranging from 1.2-fold larger at ABCA1 (P = 0.010) to 1.6-fold larger at INS (P = 3.7 × 10(-07) ). Similarly, there was more within-MZ-pair discordance in old as compared with young MZ pairs, except for GNASAS, ranging from an 8% increase in discordance each decade at CRH (P = 8.9 × 10...... spectrometry, we investigated variation in global (LINE1) DNA methylation and in DNA methylation at INS, KCNQ1OT1, IGF2, GNASAS, ABCA1, LEP, and CRH, candidate loci for common diseases. Except for KCNQ1OT1, interindividual variation in locus-specific DNA methylation was larger in old individuals than in young...

  8. Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis

    Science.gov (United States)

    2015-08-01

    exposure to the HFD or LFD, obese mice weighed significantly greater than lean mice (p=0.003, Table 1). There was no effect of HFD on non- fasted blood...AWARD NUMBER: W81XWH-13-1-0164 TITLE: Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis PRINCIPAL INVESTIGATOR: Victoria Bae...31 May 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis 5b. GRANT NUMBER

  9. The Alaska earthquake, March 27, 1964: effects on hydrologic regimen

    Science.gov (United States)

    Waller, Roger M.; Coble, R.W.; Post, Austin; McGarr, Arthur; Vorhis, Robert C.

    1966-01-01

    This is the fourth in a series of six reports that the U.S. Geological Survey published on the results of a comprehensive geologic study that began, as a reconnaissance survey, within 24 hours after the March 27, 1964, Magnitude 9.2 Great Alaska Earthquake and extended, as detailed investigations, through several field seasons. The 1964 Great Alaska earthquake was the largest earthquake in the U.S. since 1700. Professional Paper 544, in 5 parts, describes the effects on hydrologic regimen.

  10. Personality and Obesity across the Adult Lifespan

    Science.gov (United States)

    Sutin, Angelina R.; Ferrucci, Luigi; Zonderman, Alan B.; Terracciano, Antonio

    2011-01-01

    Personality traits contribute to health outcomes, in part through their association with major controllable risk factors, such as obesity. Body weight, in turn, reflects our behaviors and lifestyle and contributes to the way we perceive ourselves and others. In this study, we use data from a large (N=1,988) longitudinal study that spanned more than 50 years to examine how personality traits are associated with multiple measures of adiposity and with fluctuations in body mass index (BMI). Using 14,531 anthropometric assessments, we modeled the trajectory of BMI across adulthood and tested whether personality predicted its rate of change. Measured concurrently, participants higher on Neuroticism or Extraversion or lower on Conscientiousness had higher BMI; these associations replicated across body fat, waist, and hip circumference. The strongest association was found for the impulsivity facet: Participants who scored in the top 10% of impulsivity weighed, on average, 11Kg more than those in the bottom 10%. Longitudinally, high Neuroticism and low Conscientiousness, and the facets of these traits related to difficulty with impulse control, were associated with weight fluctuations, measured as the variability in weight over time. Finally, low Agreeableness and impulsivity-related traits predicted a greater increase in BMI across the adult lifespan. BMI was mostly unrelated to change in personality traits. Personality traits are defined by cognitive, emotional, and behavioral patterns that likely contribute to unhealthy weight and difficulties with weight management. Such associations may elucidate the role of personality traits in disease progression and may help to design more effective interventions. PMID:21744974

  11. Lowbush cranberry acts through DAF-16/FOXO signaling to promote increased lifespan and axon branching in aging posterior touch receptor neurons.

    Science.gov (United States)

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

    2018-05-01

    Medicinal berries are appreciated for their health benefits, in traditional ecological knowledge and nutrition science. Determining the cellular mechanisms underlying the effects of berry supplementation may contribute to our understanding of aging. Here, we report that lowbush cranberry (Vaccinium vitis-idaea) treatment causes marked nuclear localization of the central aging-related transcription factor DAF-16/FOXO in aged Caenorhabditis elegans. Further, functional DAF-16 is required for the lifespan extension, improved mechanosensation, and posterior touch receptor neuron morphological changes induced by lowbush cranberry treatments. DAF-16 is not observed in nuceli nor required for lifespan extension in lifespan-extending Alaskan blueberry treatments and, while DAF-16 is not visibly induced into the nucleus in lifespan-extending Alaskan chaga treatments, it is required for chaga-induced lifespan extension. These findings underscore the importance of DAF-16 in the aging of whole organisms and touch receptor neurons and also, importantly, indicate that this critical pathway is not always activated upon consumption of functional foods that impact aging.

  12. Why men matter: mating patterns drive evolution of human lifespan.

    Directory of Open Access Journals (Sweden)

    Shripad D Tuljapurkar

    2007-08-01

    Full Text Available Evolutionary theory predicts that senescence, a decline in survival rates with age, is the consequence of stronger selection on alleles that affect fertility or mortality earlier rather than later in life. Hamilton quantified this argument by showing that a rare mutation reducing survival is opposed by a selective force that declines with age over reproductive life. He used a female-only demographic model, predicting that female menopause at age ca. 50 yrs should be followed by a sharp increase in mortality, a "wall of death." Human lives obviously do not display such a wall. Explanations of the evolution of lifespan beyond the age of female menopause have proven difficult to describe as explicit genetic models. Here we argue that the inclusion of males and mating patterns extends Hamilton's theory and predicts the pattern of human senescence. We analyze a general two-sex model to show that selection favors survival for as long as men reproduce. Male fertility can only result from matings with fertile females, and we present a range of data showing that males much older than 50 yrs have substantial realized fertility through matings with younger females, a pattern that was likely typical among early humans. Thus old-age male fertility provides a selective force against autosomal deleterious mutations at ages far past female menopause with no sharp upper age limit, eliminating the wall of death. Our findings illustrate the evolutionary importance of males and mating preferences, and show that one-sex demographic models are insufficient to describe the forces that shape human senescence.

  13. Crosstalk between mitochondrial stress signals regulates yeast chronological lifespan.

    Science.gov (United States)

    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.

  14. New Treatment Regimen for Latent Tuberculosis Infection

    Centers for Disease Control (CDC) Podcasts

    In this podcast, Dr. Kenneth Castro, Director of the Division of Tuberculosis Elimination, discusses the December 9, 2011 CDC guidelines for the use of a new regimen for the treatment of persons with latent tuberculosis infection.

  15. Extended Emotions

    DEFF Research Database (Denmark)

    Krueger, Joel; Szanto, Thomas

    2016-01-01

    beyond the neurophysiological confines of organisms; some even argue that emotions can be socially extended and shared by multiple agents. Call this the extended emotions thesis (ExE). In this article, we consider different ways of understanding ExE in philosophy, psychology, and the cognitive sciences...

  16. A regulated response to impaired respiration slows behavioral rates and increases lifespan in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    David Cristina

    2009-04-01

    Full Text Available When mitochondrial respiration or ubiquinone production is inhibited in Caenorhabditis elegans, behavioral rates are slowed and lifespan is extended. Here, we show that these perturbations increase the expression of cell-protective and metabolic genes and the abundance of mitochondrial DNA. This response is similar to the response triggered by inhibiting respiration in yeast and mammalian cells, termed the "retrograde response". As in yeast, genes switched on in C. elegans mitochondrial mutants extend lifespan, suggesting an underlying evolutionary conservation of mechanism. Inhibition of fstr-1, a potential signaling gene that is up-regulated in clk-1 (ubiquinone-defective mutants, and its close homolog fstr-2 prevents the expression of many retrograde-response genes and accelerates clk-1 behavioral and aging rates. Thus, clk-1 mutants live in "slow motion" because of a fstr-1/2-dependent pathway that responds to ubiquinone. Loss of fstr-1/2 does not suppress the phenotypes of all long-lived mitochondrial mutants. Thus, although different mitochondrial perturbations activate similar transcriptional and physiological responses, they do so in different ways.

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

    Directory of Open Access Journals (Sweden)

    Seung-Il Oh

    2015-05-01

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

  18. Sex-specific lifespan and its evolution in nematodes.

    Science.gov (United States)

    Ancell, Henry; Pires-daSilva, Andre

    2017-10-01

    Differences between sexes of the same species in lifespan and aging rate are widespread. While the proximal and evolutionary causes of aging are well researched, the factors that contribute to sex differences in these traits have been less studied. The striking diversity of nematodes provides ample opportunity to study variation in sex-specific lifespan patterns associated with shifts in life history and mating strategy. Although the plasticity of these sex differences will make it challenging to generalize from invertebrate to vertebrate systems, studies in nematodes have enabled empirical evaluation of predictions regarding the evolution of lifespan. These studies have highlighted how natural and sexual selection can generate divergent patterns of lifespan if the sexes are subject to different rates or sources of mortality, or if trade-offs between complex traits and longevity are resolved differently in each sex. Here, we integrate evidence derived mainly from nematodes that addresses the molecular and evolutionary basis of sex-specific aging and lifespan. Ultimately, we hope to generate a clearer picture of current knowledge in this area, and also highlight the limitations of our understanding. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Understanding retirement: the promise of life-span developmental frameworks.

    Science.gov (United States)

    Löckenhoff, Corinna E

    2012-09-01

    The impending retirement of large population cohorts creates a pressing need for practical interventions to optimize outcomes at the individual and societal level. This necessitates comprehensive theoretical models that acknowledge the multi-layered nature of the retirement process and shed light on the dynamic mechanisms that drive longitudinal patterns of adjustment. The present commentary highlights ways in which contemporary life-span developmental frameworks can inform retirement research, drawing on the specific examples of Bronfenbrenner's Ecological Model, Baltes and Baltes Selective Optimization with Compensation Framework, Schulz and Heckhausen's Motivational Theory of Life-Span Development, and Carstensen's Socioemotional Selectivity Theory. Ultimately, a life-span developmental perspective on retirement offers not only new interpretations of known phenomena but may also help to identify novel directions for future research as well as promising pathways for interventions.

  20. 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...

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

    Directory of Open Access Journals (Sweden)

    Brian H Lee

    2008-10-01

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

  2. Prophylactic antibiotic regimens in tumour surgery (PARITY)

    DEFF Research Database (Denmark)

    Petersen, Michael Mørk; Hettwer, Werner H; Grum-Schwensen, Tomas

    2015-01-01

    -day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. METHODS: We performed a pilot international multi-centre RCT. We used central randomisation...... to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. RESULTS: We screened 96 patients and enrolled 60 participants......% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. CONCLUSIONS: It is feasible to conduct a definitive multi-centre RCT of post...

  3. Telomeres and the natural lifespan limit in humans

    DEFF Research Database (Denmark)

    Steenstrup, Troels; Kark, Jeremy D; Verhulst, Simon

    2017-01-01

    An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal...... natural lifespan limit. We define leukocyte telomere length of 5 kb as the 'telomeric brink', which denotes a high risk of imminent death. We show that a subset of adults may reach the telomeric brink within the current life expectancy and more so for a 100-year life expectancy. Thus, secular trends...

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Extended thermodynamics

    CERN Document Server

    Müller, Ingo

    1993-01-01

    Physicists firmly believe that the differential equations of nature should be hyperbolic so as to exclude action at a distance; yet the equations of irreversible thermodynamics - those of Navier-Stokes and Fourier - are parabolic. This incompatibility between the expectation of physicists and the classical laws of thermodynamics has prompted the formulation of extended thermodynamics. After describing the motifs and early evolution of this new branch of irreversible thermodynamics, the authors apply the theory to mon-atomic gases, mixtures of gases, relativistic gases, and "gases" of phonons and photons. The discussion brings into perspective the various phenomena called second sound, such as heat propagation, propagation of shear stress and concentration, and the second sound in liquid helium. The formal mathematical structure of extended thermodynamics is exposed and the theory is shown to be fully compatible with the kinetic theory of gases. The study closes with the testing of extended thermodynamics thro...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    mitochondrial transcripts were decreased, particularly in the highly oxidative soleus muscle, we found no consistent change in mitochondrial DNA or protein levels. In agreement with the lack of change in mitochondrial components, rapamycin-treated mice had endurance equivalent to that of untreated controls...

  7. Loss of NDG-4 extends lifespan and stress resistance in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Brejning, Jeanette; Nørgaard, Steffen; Schøler, Lone Vedel

    2014-01-01

    NDG-4 is a predicted transmembrane acyltransferase protein that acts in the distribution of lipophilic factors. Consequently, ndg-4 mutants lay eggs with a pale appearance due to lack of yolk, and they are resistant to sterility caused by dietary supplementation with the long-chain omega-6 polyun...

  8. Telomerase levels control the lifespan of human T lymphocytes

    NARCIS (Netherlands)

    Roth, Alexander; Yssel, Hans; Pene, Jerome; Chavez, Elizabeth A.; Schertzer, Mike; Lansdorp, Peter M.; Spits, Hergen; Luiten, Rosalie M.

    2003-01-01

    The loss of telomeric DNA with each cell division contributes to the limited replicative lifespan of human T lymphocytes. Although telomerase is transiently expressed in T lymphocytes upon activation, it is insufficient to confer immortality. We have previously shown that immortalization of human

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

    NARCIS (Netherlands)

    Jaspers, Esther; Pieters, Rik

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

  10. Lifespan Differences in the Social Networks of Prison Inmates

    Science.gov (United States)

    Bond, Gary D.; Thompson, Laura A.; Malloy, Daniel M.

    2005-01-01

    Socioemotional Selectivity Theory (SST) (Carstensen, 1992, 1993) accounts for lifespan changes in human social networks and for the motivations which underlie those changes. SST is applied in this research with 256 prison inmates and non-inmates, ages 18-84, from Mississippi, Kansas, and New Mexico. Two research questions sought to identify (a)…

  11. Extension of mouse lifespan by overexpression of catalase.

    Science.gov (United States)

    Schriner, Samuel E; Linford, Nancy J

    2006-06-01

    The free radical theory of aging was originally proposed 50 years ago, and is arguably the most popular mechanism explaining the aging process. According to this theory, aging results from the progressive decline in organ function due to the damage generated by reactive oxygen species (ROS). These chemical species are a normal part of metabolism, and a group of enzymes exists to protect cells against their toxic effects. One of these species is hydrogen peroxide (H(2)O(2)), which can be degraded by catalase. To determine the role of hydrogen peroxide in aging and its importance in different subcellular compartments, transgenic mice were developed with increased catalase activities localized to the peroxisome (PCAT), nucleus (NCAT), or mitochondrion (MCAT). The largest effect on lifespan was found in MCAT animals, with a 20% increase in median lifespan and a 10% increase in the maximum lifespan. A more modest effect was seen in PCAT animals, and no significant change was found in NCAT animals. Upon further examination of the MCAT mice, it was found that H(2)O(2) production and H(2)O(2)-induced aconitase inactivation were attenuated, oxidative damage and the development of mitochondrial deletions were reduced, and cardiac pathology and cataract development were delayed. These results are consistent with a role of H(2)O(2) in the development of pathology and in the limitation of mouse lifespan. They also demonstrate the importance of mitochondria as a source, and possible target, of ROS.

  12. Implications of Methodist clergies' average lifespan and missional ...

    African Journals Online (AJOL)

    2015-06-09

    Jun 9, 2015 ... The author of Genesis 5 paid meticulous attention to the lifespan of several people ... of Southern Africa (MCSA), and to argue that memories of the ... average ages at death were added up and the sum was divided by 12 (which represents the 12 ..... not explicit in how the departed Methodist ministers were.

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

    NARCIS (Netherlands)

    Derkx, P.H.J.M.

    2006-01-01

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

  14. Modality Differences in Timing and Temporal Memory throughout the Lifespan

    Science.gov (United States)

    Lustig, Cindy; Meck, Warren H.

    2011-01-01

    The perception of time is heavily influenced by attention and memory, both of which change over the lifespan. In the current study, children (8 yrs), young adults (18-25 yrs), and older adults (60-75 yrs) were tested on a duration bisection procedure using 3 and 6-s auditory and visual signals as anchor durations. During test, participants were…

  15. The reproductive lifespan of Onchocerca volvulus in West African savanna

    NARCIS (Netherlands)

    A.P. Plaisier (Anton); G.J. van Oortmarssen (Gerrit); J.H.F. Remme (Jan); J.D.F. Habbema (Dik)

    1991-01-01

    markdownabstractAbstract The epidemiological model ONCHOSIM — a model and computer simulation program for the transmission and control of onchocerciasis — has been used to determine the range of plausible values for the reproductive lifespan of Onchocerca volvulus. Model predictions based on

  16. Lack of Ach1 CoA-Transferase Triggers Apoptosis and Decreases Chronological Lifespan in Yeast

    International Nuclear Information System (INIS)

    Orlandi, Ivan; Casatta, Nadia; Vai, Marina

    2012-01-01

    ACH1 encodes a mitochondrial enzyme of Saccharomyces cerevisiae endowed with CoA-transferase activity. It catalyzes the CoASH transfer from succinyl-CoA to acetate generating acetyl-CoA. It is known that ACH1 inactivation results in growth defects on media containing acetate as a sole carbon and energy source which are particularly severe at low pH. Here, we show that chronological aging ach1Δ cells which accumulate a high amount of extracellular acetic acid display a reduced chronological lifespan. The faster drop of cell survival is completely abrogated by alleviating the acid stress either by a calorie restricted regimen that prevents acetic acid production or by transferring chronologically aging mutant cells to water. Moreover, the short-lived phenotype of ach1Δ cells is accompanied by reactive oxygen species accumulation, severe mitochondrial damage, and an early insurgence of apoptosis. A similar pattern of endogenous severe oxidative stress is observed when ach1Δ cells are cultured using acetic acid as a carbon source under acidic conditions. On the whole, our data provide further evidence of the role of acetic acid as cell-extrinsic mediator of cell death during chronological aging and highlight a primary role of Ach1 enzymatic activity in acetic acid detoxification which is important for mitochondrial functionality.

  17. Extending Puppet

    CERN Document Server

    Franceschi, Alessandro

    2014-01-01

    This book is a clear, detailed and practical guide to learn about designing and deploying you puppet architecture, with informative examples to highlight and explain concepts in a focused manner. This book is designed for users who already have good experience with Puppet, and will surprise experienced users with innovative topics that explore how to design, implement, adapt, and deploy a Puppet architecture. The key to extending Puppet is the development of types and providers, for which you must be familiar with Ruby.

  18. Vitellogenin family gene expression does not increase Drosophila lifespan or fecundity [v1; ref status: indexed, http://f1000r.es/3ac

    Directory of Open Access Journals (Sweden)

    Yingxue Ren

    2014-06-01

    Full Text Available One of the most striking patterns in comparative biology is the negative correlation between lifespan and fecundity observed in comparisons among species. This pattern is consistent with the idea that organisms need to allocate a fixed energy budget among competing demands of growth, development, reproduction and somatic maintenance. However, exceptions to this pattern have been observed in many social insects, including ants, bees, and termites.  In honey bees (Apis mellifera, Vitellogenin (Vg, a yolk protein precursor, has been implicated in mediating the long lifespan and high fecundity of queen bees. To determine if Vg-like proteins can regulate lifespan in insects generally, we examined the effects of expression of Apis Vg and Drosophila CG31150 (a Vg-like gene recently identified as cv-d on Drosophila melanogaster lifespan and fecundity using the RU486-inducible GeneSwitch system. For all genotypes tested, overexpression of Vg and CG31150 decreased Drosophila lifespan and did not affect total or age-specific fecundity. We also detected an apparent effect of the GeneSwitch system itself, wherein RU486 exposure (or the GAL4 expression it induces led to a significant increase in longevity and decrease in fecundity in our fly strains. This result is consistent with the pattern reported in a recent meta-analysis of Drosophila aging studies, where transgenic constructs of the UAS/GAL4 expression system that should have no effect (e.g. an uninduced GeneSwitch significantly extended lifespan in some genetic backgrounds. Our results suggest that Vg-family genes are not major regulators of Drosophila life history traits, and highlight the importance of using appropriate controls in aging studies.

  19. Systematic analysis of asymmetric partitioning of yeast proteome between mother and daughter cells reveals “aging factors” and mechanism of lifespan asymmetry

    Science.gov (United States)

    Yang, Jing; McCormick, Mark A.; Zheng, Jiashun; Xie, Zhengwei; Tsuchiya, Mitsuhiro; Tsuchiyama, Scott; El-Samad, Hana; Ouyang, Qi; Kaeberlein, Matt; Kennedy, Brian K.; Li, Hao

    2015-01-01

    Budding yeast divides asymmetrically, giving rise to a mother cell that progressively ages and a daughter cell with full lifespan. It is generally assumed that mother cells retain damaged, lifespan limiting materials (“aging factors”) through asymmetric division. However, the identity of these aging factors and the mechanisms through which they limit lifespan remain poorly understood. Using a flow cytometry-based, high-throughput approach, we quantified the asymmetric partitioning of the yeast proteome between mother and daughter cells during cell division, discovering 74 mother-enriched and 60 daughter-enriched proteins. While daughter-enriched proteins are biased toward those needed for bud construction and genome maintenance, mother-enriched proteins are biased towards those localized in the plasma membrane and vacuole. Deletion of 23 of the 74 mother-enriched proteins leads to lifespan extension, a fraction that is about six times that of the genes picked randomly from the genome. Among these lifespan-extending genes, three are involved in endosomal sorting/endosome to vacuole transport, and three are nitrogen source transporters. Tracking the dynamic expression of specific mother-enriched proteins revealed that their concentration steadily increases in the mother cells as they age, but is kept relatively low in the daughter cells via asymmetric distribution. Our results suggest that some mother-enriched proteins may increase to a concentration that becomes deleterious and lifespan-limiting in aged cells, possibly by upsetting homeostasis or leading to aberrant signaling. Our study provides a comprehensive resource for analyzing asymmetric cell division and aging in yeast, which should also be valuable for understanding similar phenomena in other organisms. PMID:26351681

  20. Systematic analysis of asymmetric partitioning of yeast proteome between mother and daughter cells reveals "aging factors" and mechanism of lifespan asymmetry.

    Science.gov (United States)

    Yang, Jing; McCormick, Mark A; Zheng, Jiashun; Xie, Zhengwei; Tsuchiya, Mitsuhiro; Tsuchiyama, Scott; El-Samad, Hana; Ouyang, Qi; Kaeberlein, Matt; Kennedy, Brian K; Li, Hao

    2015-09-22

    Budding yeast divides asymmetrically, giving rise to a mother cell that progressively ages and a daughter cell with full lifespan. It is generally assumed that mother cells retain damaged, lifespan limiting materials ("aging factors") through asymmetric division. However, the identity of these aging factors and the mechanisms through which they limit lifespan remain poorly understood. Using a flow cytometry-based, high-throughput approach, we quantified the asymmetric partitioning of the yeast proteome between mother and daughter cells during cell division, discovering 74 mother-enriched and 60 daughter-enriched proteins. While daughter-enriched proteins are biased toward those needed for bud construction and genome maintenance, mother-enriched proteins are biased towards those localized in the plasma membrane and vacuole. Deletion of 23 of the 74 mother-enriched proteins leads to lifespan extension, a fraction that is about six times that of the genes picked randomly from the genome. Among these lifespan-extending genes, three are involved in endosomal sorting/endosome to vacuole transport, and three are nitrogen source transporters. Tracking the dynamic expression of specific mother-enriched proteins revealed that their concentration steadily increases in the mother cells as they age, but is kept relatively low in the daughter cells via asymmetric distribution. Our results suggest that some mother-enriched proteins may increase to a concentration that becomes deleterious and lifespan-limiting in aged cells, possibly by upsetting homeostasis or leading to aberrant signaling. Our study provides a comprehensive resource for analyzing asymmetric cell division and aging in yeast, which should also be valuable for understanding similar phenomena in other organisms.

  1. New Treatment Regimen for Latent Tuberculosis Infection

    Centers for Disease Control (CDC) Podcasts

    2012-03-15

    In this podcast, Dr. Kenneth Castro, Director of the Division of Tuberculosis Elimination, discusses the December 9, 2011 CDC guidelines for the use of a new regimen for the treatment of persons with latent tuberculosis infection.  Created: 3/15/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 3/15/2012.

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

    Science.gov (United States)

    Habermas, Tilmann; Diel, Verena; Welzer, Harald

    2013-09-01

    Autobiographical memories of older adults show fewer episodic and more non-episodic elements than those of younger adults. This semantization effect is attributed to a loss of episodic memory ability. However the alternative explanation by an increasing proclivity to search for meaning has not been ruled out to date. To test whether a decrease in episodicity and an increase in meaning-making in autobiographical narratives are related across the lifespan, we used different instructions, one focussing on specific episodes, the other on embedding events in life, in two lifespan samples. A continuous decrease of episodic quality of memory (memory specificity, narrative quality) was confirmed. An increase of search for meaning (interpretation, life story integration) was confirmed only up to middle adulthood. This non-inverse development of episodicity and searching for meaning in older age speaks for an autonomous semantization effect that is not merely due to an increase in interpretative preferences. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Assessment of non-standard HIV antiretroviral therapy regimens at ...

    African Journals Online (AJOL)

    2016-03-06

    Mar 6, 2016 ... Most patients were transitioned to standard regimens, ... In cases of first-line regimen treatment failure, ..... tute; National Heart, Lung, and Blood Institute; National. Institute of Dental & Craniofacial Research; National Insti-.

  4. Consciousness extended

    DEFF Research Database (Denmark)

    Carrara-Augustenborg, Claudia

    2012-01-01

    There is no consensus yet regarding a conceptualization of consciousness able to accommodate all the features of such complex phenomenon. Different theoretical and empirical models lend strength to both the occurrence of a non-accessible informational broadcast, and to the mobilization of specific...... brain areas responsible for the emergence of the individual´s explicit and variable access to given segments of such broadcast. Rather than advocating one model over others, this chapter proposes to broaden the conceptualization of consciousness by letting it embrace both mechanisms. Within...... such extended framework, I propose conceptual and functional distinctions between consciousness (global broadcast of information), awareness (individual´s ability to access the content of such broadcast) and unconsciousness (focally isolated neural activations). My hypothesis is that a demarcation in terms...

  5. Drug synergy drives conserved pathways to increase fission yeast lifespan.

    Directory of Open Access Journals (Sweden)

    Xinhe Huang

    Full Text Available Aging occurs over time with gradual and progressive loss of physiological function. Strategies to reduce the rate of functional loss and mitigate the subsequent onset of deadly age-related diseases are being sought. We demonstrated previously that a combination of rapamycin and myriocin reduces age-related functional loss in the Baker's yeast Saccharomyces cerevisiae and produces a synergistic increase in lifespan. Here we show that the same drug combination also produces a synergistic increase in the lifespan of the fission yeast Schizosaccharomyces pombe and does so by controlling signal transduction pathways conserved across a wide evolutionary time span ranging from yeasts to mammals. Pathways include the target of rapamycin complex 1 (TORC1 protein kinase, the protein kinase A (PKA and a stress response pathway, which in fission yeasts contains the Sty1 protein kinase, an ortholog of the mammalian p38 MAP kinase, a type of Stress Activated Protein Kinase (SAPK. These results along with previous studies in S. cerevisiae support the premise that the combination of rapamycin and myriocin enhances lifespan by regulating signaling pathways that couple nutrient and environmental conditions to cellular processes that fine-tune growth and stress protection in ways that foster long term survival. The molecular mechanisms for fine-tuning are probably species-specific, but since they are driven by conserved nutrient and stress sensing pathways, the drug combination may enhance survival in other organisms.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  7. Intermittent food restriction initiated late in life prolongs lifespan and retards the onset of age-related markers in the annual fish Nothobranchius guentheri.

    Science.gov (United States)

    Wang, Xia; Du, Xiaoyuan; Zhou, Yang; Wang, Su; Su, Feng; Zhang, Shicui

    2017-06-01

    Two of the most studied and widely accepted conjectures on possible aging mechanisms are the oxidative stress hypothesis and the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway. Intermittent fasting (IF) is known to modulate aging and to prolong lifespan in a variety of organisms, but the mechanisms are still under debate. In this study, we first demonstrated that late-onset two consecutive days a week fasting, a form of IF, termed intermittent food restriction (IFR), exhibited a time-dependent effect, and long-term late-onset IFR extended the mean lifespan and maximum lifespan by approximately 3.5 and 3 weeks, respectively, in the annual fish Nothobranchius guentheri. We also showed that IFR reduced the accumulation of lipofuscin in the gills and the protein oxidation and lipid peroxidation levels in the muscles. Moreover, IFR was able to enhance the activities of antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase in the fish. Finally, IFR was also able to decelerate the decrease of SirT1 and Foxo3A, but accelerate the decrease of IGF-1. Collectively, our findings suggest that late-onset IFR can retard the onset of age-related markers, and prolong the lifespan of the aging fish, via a synergistic action of an anti-oxidant system and the IIS pathway. It also proposes that the combined assessment of anti-oxidant system and IIS pathway will contribute to providing a more comprehensive view of anti-aging process.

  8. Analysis of On-Board Photovoltaics for a Battery Electric Bus and Their Impact on Battery Lifespan

    Directory of Open Access Journals (Sweden)

    Kevin R. Mallon

    2017-07-01

    Full Text Available Heavy-duty electric powertrains provide a potential solution to the high emissions and low fuel economy of trucks, buses, and other heavy-duty vehicles. However, the cost, weight, and lifespan of electric vehicle batteries limit the implementation of such vehicles. This paper proposes supplementing the battery with on-board photovoltaic modules. In this paper, a bus model is created to analyze the impact of on-board photovoltaics on electric bus range and battery lifespan. Photovoltaic systems that cover the bus roof and bus sides are considered. The bus model is simulated on a suburban bus drive cycle on a bus route in Davis, CA, USA for a representative sample of yearly weather conditions. Roof-mounted panels increased vehicle driving range by 4.7% on average annually, while roof and side modules together increased driving range by 8.9%. However, variations in weather conditions meant that this additional range was not reliably available. For constant vehicle range, rooftop photovoltaic modules extended battery cycle life by up to 10% while modules on both the roof and sides extended battery cycle life by up to 19%. Although side-mounted photovoltaics increased cycle life and range, they were less weight- and cost-effective compared to the roof-mounted panels.

  9. Radiation effects on lifespan of the fish Oryzias latipes

    International Nuclear Information System (INIS)

    Egami, N.

    1979-01-01

    The mortality rate of adult fish exposed to continuous γ-ray irradiation was examined and the results summarized. Initial results into the effects of low-dose γ-irradiation during early developmental stages (one day embryo - 3 month old young) on lifespan, indicate that in this fish the life-shortening effects of radiation are marked at high doses but not at low doses. Age-related histological changes in various tissues have been observed in both irradiated and non-irradiated fish. (Auth.)

  10. Menstruation during a lifespan: A qualitative study of women's experiences.

    Science.gov (United States)

    Brantelid, Ida Emilie; Nilvér, Helena; Alehagen, Siw

    2014-01-01

    Menstruation is a natural phenomenon for women during their reproductive years. Our aim was to describe women's experiences of menstruation across the lifespan. Qualitative interviews with a narrative approach were conducted with 12 women between 18 and 48 years of age in Sweden. Using thematic analysis, we found menstruation to be a complex phenomenon that binds women together. It is perceived as an intimate and private matter, which makes women want to conceal the occurrence of menstrual bleeding. Over time, menstruation becomes a natural part of women's lives and gender identity. Health professionals play a central role supporting women to deal with menstruation.

  11. Emotional Egocentricity Bias across the life-span

    Directory of Open Access Journals (Sweden)

    Federica eRiva

    2016-04-01

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

  12. Life-span studies of inhaled plutonium in beagle dogs

    International Nuclear Information System (INIS)

    Bair, W.J.

    1990-04-01

    In 1970 a life-span study with over 300 beagle dogs was begun to gain an understanding of long-term health effects resulting from respiratory tract intakes of plutonium and to derive risk estimates that might be applied to plutonium and other transuranic elements. Groups of beagle dogs were given single exposures to 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 to obtain graded levels of initial lung burdens ranging from 1 to 1800 Bq lung. The objective of this paper is to give you a progress report on the current life-span studies of inhaled plutonium in beagle dogs at the Pacific Northwest Laboratory. I will describe the biokinetics of inhaled plutonium in dogs and the resulting health effects. I will also mention some studies directed towards understanding the mechanism leading to these effects. Finally, I will discuss the current risk estimates derived from these studies and how they might relate to plutonium exposures in humans. 5 refs., 13 figs., 4 tabs

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

    Directory of Open Access Journals (Sweden)

    Carla J. Thompson

    2013-01-01

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

  14. Sex differences in facial emotion perception ability across the lifespan.

    Science.gov (United States)

    Olderbak, Sally; Wilhelm, Oliver; Hildebrandt, Andrea; Quoidbach, Jordi

    2018-03-22

    Perception of emotion in the face is a key component of human social cognition and is considered vital for many domains of life; however, little is known about how this ability differs across the lifespan for men and women. We addressed this question with a large community sample (N = 100,257) of persons ranging from younger than 15 to older than 60 years of age. Participants were viewers of the television show "Tout le Monde Joue", and the task was presented on television, with participants responding via their mobile devices. Applying latent variable modeling, and establishing measurement invariance between males and females and across age, we found that, for both males and females, emotion perception abilities peak between the ages of 15 and 30, with poorer performance by younger adults and declining performance after the age of 30. In addition, we show a consistent advantage by females across the lifespan, which decreases in magnitude with increasing age. This large scale study with a wide range of people and testing environments suggests these effects are largely robust. Implications are discussed.

  15. On the challenge of a century lifespan satellite

    Science.gov (United States)

    Gonzalo, Jesús; Domínguez, Diego; López, Deibi

    2014-10-01

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

  16. Diosgenin a phytosterol substitute for cholesterol, prolongs the lifespan and mitigates glucose toxicity via DAF-16/FOXO and GST-4 in Caenorhabditis elegans.

    Science.gov (United States)

    Shanmugam, Govindan; Mohankumar, Amirthalingam; Kalaiselvi, Duraisamy; Nivitha, Sundararaj; Murugesh, Easwaran; Shanmughavel, Piramanayagam; Sundararaj, Palanisamy

    2017-11-01

    Caenorhabditis elegans is a sterol auxotroph requires minute amount of exogenous sterol for their growth and development. To culture the C. elegans, cholesterol was given as sterol molecule to maintain the optimum survival of worms. Diosgenin (DG), a plant derived steroidal saponin, structurally similar to cholesterol has been used as a precursor for the synthesis of steroidal hormones. In this study, worms were cultured with cholesterol (Cho + ) and cholesterol-free (Cho - ) medium with DG (5, 10 and 50μg/mL) at 20°C. It was observed that worms cultured in (Cho - ) exhibits late egg production, reduced lipid level and short lifespan, while addition of DG overcomes all defective facts. Combinations of both cholesterol and DG further extend the lifespan (20.8%), hinder lipid level and resistance to oxidative, thermal and high glucose stress. The intracellular ROS quantification was done by flouroscenic probe H2DCF-DA and confirmed that DG had significantly reduced ROS level (35.85%). Increased lifespan of worms were observed in the medium treated with DG which activates the nuclear translocation of DAF-16/FOXO transcription factor, followed by downstream antioxidant gene sod-3 as evidenced by GFP tagged strain. The expression of Phase II detoxification enzyme GST-4 significantly (pdaf-16, skn-1, and eat-2. These studies have proved that DG is a sterol source to worms and modulate the DAF-16, SOD-3 and GST-4 expression levels to extend the lifespan of worms. The present study has also highlighted the use of phytosterols as an alternative to cholesterol. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

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

  18. Mechanisms of increased lifespan in hypoxia in the alfalfa leafcutting bee, Megachile rotundata

    Science.gov (United States)

    Genetic variation accounts for a small amount of variation in lifespan, while environmental stressors are strong predictors. Hypoxia is an environmental stress that increases longevity in some contexts, but the mechanisms remain poorly understood. In the bee Megachile rotundata, lifespan doubles upo...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-07-31

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

  20. Appropriate fluid regimens to prevent bronchopulmonary dysplasia.

    Science.gov (United States)

    Tammela, O K

    1995-01-01

    Pulmonary oedema is an important problem in premature neonates with surfactant deficiency because of fluid accumulation in the lung interstitium and reduced urine output. Some retrospective reports suggest that excessive early hydration might increase the risk of bronchopulmonary dysplasia (BPD). Only three prospective studies evaluating low or conventional fluid administration regimens to very low birth weight infants have been published. According to their results no significant differences in the incidence of BPD have been shown. However, fluid restriction seems to improve the outcome of the infants because of decreased incidence of haemodynamically significant patent ductus arteriosus, necrotizing enterocolitis, pulmonary air leaks and decreased mortality. The appropriate amount of sodium in the intravenous fluids during the first days of life needs further evaluation. In tiny infants with birth weights from 500 to 800g intensive monitoring of fluid balance is essential to control the extremely high fluid losses due to evaporation. Undernutrition is a risk factor of BPD and therefore it is important to start parenteral nutrition early. The benefit of the use of colloids as volume expanders is controversial. According to some retrospective reports there might be an association with increased use of colloidal fluids during the first days of life and the development of BPD. Early excessive fluid administration might constitute a potential risk for low birth weight infants with hyaline membrane disease.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Linguistic Processing of Accented Speech Across the Lifespan

    Directory of Open Access Journals (Sweden)

    Alejandrina eCristia

    2012-11-01

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

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

    Science.gov (United States)

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

    2015-03-11

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

  3. The association between intelligence and lifespan is mostly genetic

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Several studies in the new field of cognitive epidemiology have shown that higher intelligence predicts longer lifespan. This positive correlation might arise from socioeconomic status influencing both intelligence and health; intelligence leading to better health behaviours; and....../or some shared genetic factors influencing both intelligence and health. Distinguishing among these hypotheses is crucial for medicine and public health, but can only be accomplished by studying a genetically informative sample. METHODS: We analysed data from three genetically informative samples...... containing information on intelligence and mortality: Sample 1, 377 pairs of male veterans from the NAS-NRC US World War II Twin Registry; Sample 2, 246 pairs of twins from the Swedish Twin Registry; and Sample 3, 784 pairs of twins from the Danish Twin Registry. The age at which intelligence was measured...

  4. The Sex Res Non Naturales and the Regimen of Health

    DEFF Research Database (Denmark)

    Agerholm, Frank Juul

    The paper discusses the ethical and social soundness of the classical idea of diaita/regimen vis-à-vis the contemporary focus on healthy lifestyle......The paper discusses the ethical and social soundness of the classical idea of diaita/regimen vis-à-vis the contemporary focus on healthy lifestyle...

  5. Variation in training regimens in professional showjumping yards

    NARCIS (Netherlands)

    Lönnell, A C; Bröjer, J; Nostell, K; Hernlund, E; Roepstorff, L; Tranquille, C A; Murray, R C; Oomen, A; van Weeren, René; Bitschnau, C; Montavon, S; Weishaupt, M A; Egenvall, A

    2014-01-01

    REASONS FOR PERFORMING STUDY: Training regimens of showjumping horses under field conditions are largely undocumented. OBJECTIVES: The aims of this study were to quantify and compare training regimens used in professional-level showjumping yards, with respect to time exercised and type of activity.

  6. Inappropriate Tuberculosis Treatment Regimens in Chinese Tuberculosis Hospitals

    NARCIS (Netherlands)

    Xue He, Guang; van den Hof, Susan; van der Werf, Marieke J.; Guo, Hui; Hu, Yuan Lian; Fan, Ji Huan; Zhang, Wei Min; Tostado, Christopher P.; Borgdorff, Martien W.

    2011-01-01

    This investigation of tuberculosis (TB) treatment regimens in 6 TB hospitals in China showed that only 18% of patients with new cases and 9% of patients with retreatment cases were prescribed standard TB treatment regimens. Adherence to treatment guidelines needs to be improved in TB hospitals to

  7. How teen girls think about fertility and the reproductive lifespan. Possible implications for curriculum reform and public health policy.

    Science.gov (United States)

    Littleton, Fiona Kisby

    2014-09-01

    Despite an 'epidemic' of delayed childbirth in England and Wales beyond a woman's optimally fertile years, research shows that young adults are unaware of or misunderstand the risks regarding starting or extending families that such behaviour entails. Currently, sex education syllabi in British schools neglect these issues, rendering school leavers ignorant of them.These curricula cannot be improved until more is known about adolescents' knowledge of relevant topics. In the light of this, this article describes exploratory research on how teenage girls in one English school think about the reproductive lifespan. Going beyond recent 'scientific' investigations which have mostly only tested the extent of ignorance of young adults, this qualitative enquiry used theories of the life course and emerging adulthood to analyse data gathered in interviews. It sought to understand not only what girls know, but how they apply their knowledge in relation to their assumptions about aging, motherhood, pregnancy, parenting and employment. One finding is highlighted here: that whilst "correct" knowledge about the reproductive lifespan does appear to be held by teenage girls, the ability to apply that knowledge and connect the socio-cultural with the biological domain, may not always be in place. This is relevant for curriculum developers aiming to prepare future citizens to take full control of their reproductive health, and policy makers responsible for ensuring an appropriate public health message about these concerns is available after formal schooling ends.

  8. Down syndrome: Cognitive and behavioral functioning across the lifespan.

    Science.gov (United States)

    Grieco, Julie; Pulsifer, Margaret; Seligsohn, Karen; Skotko, Brian; Schwartz, Alison

    2015-06-01

    Individuals with Down syndrome (DS) commonly possess unique neurocognitive and neurobehavioral profiles that emerge within specific developmental periods. These profiles are distinct relative to others with similar intellectual disability (ID) and reflect underlying neuroanatomic findings, providing support for a distinctive phenotypic profile. This review updates what is known about the cognitive and behavioral phenotypes associated with DS across the lifespan. In early childhood, mild deviations from neurotypically developing trajectories emerge. By school-age, delays become pronounced. Nonverbal skills remain on trajectory for mental age, whereas verbal deficits emerge and persist. Nonverbal learning and memory are strengths relative to verbal skills. Expressive language is delayed relative to comprehension. Aspects of language skills continue to develop throughout adolescence, although language skills remain compromised in adulthood. Deficits in attention/executive functions are present in childhood and become more pronounced with age. Characteristic features associated with DS (cheerful, social nature) are personality assets. Children are at a lower risk for psychopathology compared to other children with ID; families report lower levels of stress and a more positive outlook. In youth, externalizing behaviors may be problematic, whereas a shift toward internalizing behaviors emerges with maturity. Changes in emotional/behavioral functioning in adulthood are typically associated with neurodegeneration and individuals with DS are higher risk for dementia of the Alzheimer's type. Individuals with DS possess many unique strengths and weaknesses that should be appreciated as they develop across the lifespan. Awareness of this profile by professionals and caregivers can promote early detection and support cognitive and behavioral development. © 2015 Wiley Periodicals, Inc.

  9. Empirically derived lifespan polytraumatization typologies: A systematic review.

    Science.gov (United States)

    Contractor, Ateka A; Caldas, Stephanie; Fletcher, Shelley; Shea, M Tracie; Armour, Cherie

    2018-07-01

    Polytraumatization classes based on trauma endorsement patterns relate to distinct clinical outcomes. Person-centered approaches robustly evaluate the nature, and construct validity of polytraumatization classes. Our review examined evidence for the nature and construct validity of lifespan polytraumatization typologies. In September 2016, we searched Pubmed, PSYCINFO, PSYC ARTICLES, Academic Search Complete, PILPTS, Web of Science, CINAHL, Medline, PsycEXTRA, and PBSC. Search terms included "latent profile," "latent class," "latent analysis," "person-centered," "polytrauma," "polyvictimization," "traumatization," "lifetime," "cooccurring," "complex," "typology," "multidimensional," "sequential," "multiple," "subtype," "(re)victimization," "cumulative," "maltreatment," "abuse," and "stressor." Inclusionary criteria included: peer-reviewed; latent class/latent profile analyses (LCA/LPA) of lifespan polytrauma classes; adult samples of size greater than 200; only trauma types as LCA/LPA indicators; mental health correlates of typologies; and individual-level trauma assessment. Of 1,397 articles, nine met inclusion criteria. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, research assistants completed a secondary reference search, and independently extracted data with standardized coding forms. Three-class (n = 5) or four-class (n = 4) solutions were found. Seven studies found a class characterized by higher trauma endorsement (high-trauma). All studies found a class characterized by lower trauma endorsement (low-trauma), and predominance of specific traumas (specific-trauma; e.g., childhood maltreatment). High-trauma versus low-trauma classes and specific-trauma versus low-trauma classes differed on mental health correlates. Evidence supports the prevalence of a high-trauma class experiencing poorer mental health, and the detrimental impact of aggregated interpersonal and other traumas. We highlight the clinical

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

    Directory of Open Access Journals (Sweden)

    Michal Engelman

    2014-05-01

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

  11. Different Temporal Patterns of Specific and General Autobiographical Memories across the Lifespan in Alzheimer's Disease.

    Science.gov (United States)

    Philippi, Nathalie; Rousseau, François; Noblet, Vincent; Botzung, Anne; Després, Olivier; Cretin, Benjamin; Kremer, Stéphane; Blanc, Frédéric; Manning, Liliann

    2015-01-01

    We compared specific (i.e., associated with a unique time and space) and general (i.e., extended or repeated events) autobiographical memories (AbM) in Alzheimer's disease (AD). The comparison aims at investigating the relationship between these two components of AbM across the lifespan and the volume of cerebral regions of interest within the temporal lobe. We hypothesized that the ability to elicit specific memories would correlate with hippocampal volume, whereas evoking general memories would be related to lateral temporal lobe. AbM was assessed using the modified Crovitz test in 18 patients with early AD and 18 matched controls. The proportions of total memories-supposed to reflect the ability to produce general memories-and specific memories retrieved were compared between AD patients and controls. Correlations to MRI volumes of temporal cortex were tested. We found different temporal patterns for specific and general memories in AD patients, with (i) relatively spared general memories, according to a temporal gradient that preserved remote memories, predominantly associated with right lateral temporal cortex volume. (ii) Conversely, the retrieval of specific AbMs was impaired for all life periods and correlated with bilateral hippocampal volumes. Our results highlight a shift from an initially episodic to a semantic nature of AbMs during AD, where the abstracted form of memories remains.

  12. Calorie Restriction-Mediated Replicative Lifespan Extension in Yeast Is Non-Cell Autonomous

    Science.gov (United States)

    Mei, Szu-Chieh; Brenner, Charles

    2015-01-01

    In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR) to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA), are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR) allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell. PMID:25633578

  13. Calorie restriction-mediated replicative lifespan extension in yeast is non-cell autonomous.

    Directory of Open Access Journals (Sweden)

    Szu-Chieh Mei

    2015-01-01

    Full Text Available In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA, are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell.

  14. Lifetime return on investment increases with leaf lifespan among 10 Australian woodland species.

    Science.gov (United States)

    Falster, Daniel S; Reich, Peter B; Ellsworth, David S; Wright, Ian J; Westoby, Mark; Oleksyn, Jacek; Lee, Tali D

    2012-01-01

    • Co-occurring species often differ in their leaf lifespan (LL) and it remains unclear how such variation is maintained in a competitive context. Here we test the hypothesis that leaves of long-LL species yield a greater return in carbon (C) fixed per unit C or nutrient invested by the plant than those of short-LL species. • For 10 sympatric woodland species, we assessed three-dimensional shoot architecture, canopy openness, leaf photosynthetic light response, leaf dark respiration and leaf construction costs across leaf age sequences. We then used the YPLANT model to estimate light interception and C revenue along the measured leaf age sequences. This was done under a series of simulations that incorporated the potential covariates of LL in an additive fashion. • Lifetime return in C fixed per unit C, N or P invested increased with LL in all simulations. • In contrast to other recent studies, our results show that extended LL confers a fundamental economic advantage by increasing a plant's return on investment in leaves. This suggests that time-discounting effects, that is, the compounding of income that arises from quick reinvestment of C revenue, are key in allowing short-LL species to succeed in the face of this economic handicap. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

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

    Science.gov (United States)

    Fang, Evandro Fei; Kassahun, Henok; Croteau, Deborah L; Scheibye-Knudsen, Morten; Marosi, Krisztina; Lu, Huiming; Shamanna, Raghavendra A; Kalyanasundaram, Sumana; Bollineni, Ravi Chand; Wilson, Mark A; Iser, Wendy B; Wollman, Bradley N; Morevati, Marya; Li, Jun; Kerr, Jesse S; Lu, Qiping; Waltz, Tyler B; Tian, Jane; Sinclair, David A; Mattson, Mark P; Nilsen, Hilde; Bohr, Vilhelm A

    2016-10-11

    Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive neurodegeneration and cerebellar ataxia. A-T is causally linked to defects in ATM, a master regulator of the response to and repair of DNA double-strand breaks. The molecular basis of cerebellar atrophy and neurodegeneration in A-T patients is unclear. Here we report and examine the significance of increased PARylation, low NAD + , and mitochondrial dysfunction in ATM-deficient neurons, mice, and worms. Treatments that replenish intracellular NAD + reduce the severity of A-T neuropathology, normalize neuromuscular function, delay memory loss, and extend lifespan in both animal models. Mechanistically, treatments that increase intracellular NAD + also stimulate neuronal DNA repair and improve mitochondrial quality via mitophagy. This work links two major theories on aging, DNA damage accumulation, and mitochondrial dysfunction through nuclear DNA damage-induced nuclear-mitochondrial signaling, and demonstrates that they are important pathophysiological determinants in premature aging of A-T, pointing to therapeutic interventions. Published by Elsevier Inc.

  16. Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin

    Directory of Open Access Journals (Sweden)

    Julia Ring

    2017-11-01

    Full Text Available Hereditary spastic paraplegias, a group of neurodegenerative disorders, can be caused by loss-of-function mutations in the protein spartin. However, the physiological role of spartin remains largely elusive. Here we show that heterologous expression of human or Drosophila spartin extends chronological lifespan of yeast, reducing age-associated ROS production, apoptosis, and necrosis. We demonstrate that spartin localizes to the proximity of mitochondria and physically interacts with proteins related to mitochondrial and respiratory metabolism. Interestingly, Nde1, the mitochondrial external NADH dehydrogenase, and Pda1, the core enzyme of the pyruvate dehydrogenase complex, are required for spartin-mediated cytoprotection. Furthermore, spartin interacts with the glycolysis enhancer phospo-fructo-kinase-2,6 (Pfk26 and is sufficient to complement for PFK26-deficiency at least in early aging. We conclude that mitochondria-related energy metabolism is crucial for spartin’s vital function during aging and uncover a network of specific interactors required for this function.

  17. Polyhydroxy fullerenes (fullerols or fullerenols: beneficial effects on growth and lifespan in diverse biological models.

    Directory of Open Access Journals (Sweden)

    Jie Gao

    Full Text Available Recent toxicological studies on carbon nanomaterials, including fullerenes, have led to concerns about their safety. Functionalized fullerenes, such as polyhydroxy fullerenes (PHF, fullerols, or fullerenols, have attracted particular attention due to their water solubility and toxicity. Here, we report surprisingly beneficial and/or specific effects of PHF on model organisms representing four kingdoms, including the green algae Pseudokirchneriella subcapitata, the plant Arabidopsis thaliana, the fungus Aspergillus niger, and the invertebrate Ceriodaphnia dubia. The results showed that PHF had no acute or chronic negative effects on the freshwater organisms. Conversely, PHF could surprisingly increase the algal culture density over controls at higher concentrations (i.e., 72% increase by 1 and 5 mg/L of PHF and extend the lifespan and stimulate the reproduction of Daphnia (e.g. about 38% by 20 mg/L of PHF. We also show that at certain PHF concentrations fungal growth can be enhanced and Arabidopsis thaliana seedlings exhibit longer hypocotyls, while other complex physiological processes remain unaffected. These findings may open new research fields in the potential applications of PHF, e.g., in biofuel production and aquaculture. These results will form the basis of further research into the mechanisms of growth stimulation and life extension by PHF.

  18. Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings

    OpenAIRE

    Trepanowski, John F; Canale, Robert E; Marshall, Kate E; Kabir, Mohammad M; Bloomer, Richard J

    2011-01-01

    Abstract Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE) consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF) consists of two interchanging days; one...

  19. A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension.

    Science.gov (United States)

    Cavuoto, Paul; Fenech, Michael F

    2012-10-01

    Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Drug susceptibility of Mycobacterium tuberculosis in a rural area of Bangladesh and its relevance to the national treatment regimens.

    Science.gov (United States)

    Van Deun, A; Aung, K J; Chowdhury, S; Saha, S; Pankaj, A; Ashraf, A; Rigouts, L; Fissette, K; Portaels, F

    1999-02-01

    Greater Mymensingh District, a rural area of Bangladesh, at the start of the National Tuberculosis Programme (NTP). To determine the prevalence of initial and acquired drug resistance of Mycobacterium tuberculosis, and to assess the appropriateness of the NTP's standard regimens. Sampling of pre-treatment sputum from all newly registered smear-positive cases in five centres covering the area. Culture and susceptibility testing in a supra-national reference laboratory. Initial resistance to isoniazid (H) was 5.4%, and to rifampicin (R) 0.5%. Acquired H and R resistance were 25.9% and 7.4%, respectively. Multidrug resistance (MDR) was observed in one new case only and in 5.6% of previously treated patients. Changing the present NTP indication for retreatment regimen to one month of previous H intake would increase coverage of H-resistant cases from 52% to 89%, adding 6% to drug costs. The prevalence of drug resistance is surprisingly low in Bangladesh, but could rise with improving economic conditions. The NTP regimens for smear-positive cases are appropriate, all the more so since the human immunodeficiency virus is virtually absent. Indications for the retreatment regimen should be extended to include all patients treated for at least one month with any drug. The NTP regimen for smear-negative cases runs the risk of leading to MDR under present field conditions.

  1. Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression

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    Liangping Su

    2018-03-01

    Full Text Available Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3 in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway. In set-18 mutants, transcription of daf-16 isoform a (daf-16a was specifically upregulated. Accordingly, a decrease in H3K36me2 on daf-16a promoter was observed. Muscle-specific expression of SET-18 increased in aged worms (day 7 and day 11, attributable to elevation of global H3K36me2 and inhibition of daf-16a expression. Consequently, longevity was shortened. These findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases.

  2. Defected red blood cell membranes and direct correlation with the uraemic milieu: the connection with the decreased red blood cell lifespan observed in haemodialysis patients

    International Nuclear Information System (INIS)

    Stamopoulos, D; Manios, E; Gogola, V; Grapsa, E; Bakirtzi, N

    2012-01-01

    Together with impaired production of erythropoietin and iron deficiency, the decreased lifespan of red blood cells (RBCs) is a main factor contributing to the chronic anaemia observed in haemodialysis (HD) patients. Atomic force microscopy is employed in this work to thoroughly survey the membrane of intact RBCs (iRBCs) of HD patients in comparison to those of healthy donors, aiming to obtain direct information on the structural status of RBCs that can be related to their decreased lifespan. We observed that the iRBC membrane of the HD patients is overpopulated with extended circular defects, termed ‘orifices’, that have typical dimension ranging between 0.2 and 1.0 μm. The ‘orifice’ index—that is, the mean population of ‘orifices’ per top membrane surface—exhibits a pronounced relative increase of order 54 ± 12% for the HD patients as compared to healthy donors. Interestingly, for the HD patients, the ‘orifice’ index, which relates to the structural status of the RBC membrane, correlates strongly with urea concentration, which is a basic index of the uraemic milieu. Thus, these results indicate that the uraemic milieu downgrades the structural status of the RBC membrane, possibly triggering biochemical processes that result in their premature elimination from the circulation. This process could decrease the lifespan of RBCs, as observed in HD patients. (paper)

  3. Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression.

    Science.gov (United States)

    Su, Liangping; Li, Hongyuan; Huang, Cheng; Zhao, Tingting; Zhang, Yongjun; Ba, Xueqing; Li, Zhongwei; Zhang, Yu; Huang, Baiqu; Lu, Jun; Zhao, Yanmei; Li, Xiaoxue

    2018-03-06

    Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3) in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway. In set-18 mutants, transcription of daf-16 isoform a (daf-16a) was specifically upregulated. Accordingly, a decrease in H3K36me2 on daf-16a promoter was observed. Muscle-specific expression of SET-18 increased in aged worms (day 7 and day 11), attributable to elevation of global H3K36me2 and inhibition of daf-16a expression. Consequently, longevity was shortened. These findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Starving for life: what animal studies can and cannot tell us about the use of caloric restriction to prolong human lifespan.

    Science.gov (United States)

    Speakman, John R; Hambly, Catherine

    2007-04-01

    Caloric restriction (CR) is the only experimental nongenetic paradigm known to increase lifespan. It has broad applicability and extends the life of most species through a retardation of aging. There is considerable interest in the use of CR in humans, and animal studies can potentially tell us about the impacts. In this article we highlight some of the things that animal studies can tell us about CR in humans. Rodent studies indicate that the benefits of CR on lifespan extension are related to the extent of restriction. The benefits of CR, however, decline as the age of onset of treatment is delayed. Modeling these impacts suggests that if a 48-y-old man engaged in 30% CR until his normal life expectancy of 78, he might increase his life expectancy by 2.8 y. Exercise and cold exposure induce similar energy deficits, but animals respond to these energy deficits in different ways that have a minor impact on lifespan. Measurements of animal responses when they cease restriction indicate that prolonged CR does not diminish hunger, even though the animals may have been in long-term energy balance. Neuroendocrine profiles support the idea that animals under CR are continuously hungry. The feasibility of restricting intake in humans for many decades without long-term support is questionable. However, what is unclear from animal studies is whether taking drugs that suppress appetite will generate the same impact on longevity or whether the neuroendocrine correlates of hunger play an integral role in mediating CRs effects.

  5. Tomatidine enhances lifespan and healthspan in C. elegans through mitophagy induction via the SKN-1/Nrf2 pathway

    DEFF Research Database (Denmark)

    Fang, Evandro Fei; Waltz, Tyler B; Kassahun, Henok

    2017-01-01

    in human aging. Tomatidine, a natural compound abundant in unripe tomatoes, inhibits age-related skeletal muscle atrophy in mice. Here we show that tomatidine extends lifespan and healthspan in C. elegans, an animal model of aging which shares many major longevity pathways with mammals. Tomatidine improves...... many C. elegans behaviors related to healthspan and muscle health, including increased pharyngeal pumping, swimming movement, and reduced percentage of severely damaged muscle cells. Microarray, imaging, and behavioral analyses reveal that tomatidine maintains mitochondrial homeostasis by modulating...... occurs in C. elegans, primary rat neurons, and human cells. Our data suggest that tomatidine may delay some physiological aspects of aging, and points to new approaches for pharmacological interventions for diseases of aging....

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

    Science.gov (United States)

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

    2017-01-01

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

  7. Transcriptome analysis of a long-lived natural Drosophila variant: a prominent role of stress- and reproduction-genes in lifespan extension

    Directory of Open Access Journals (Sweden)

    Doroszuk Agnieszka

    2012-05-01

    Full Text Available Abstract Background While studying long-lived mutants has advanced our understanding of the processes involved in ageing, the mechanisms underlying natural variation in lifespan and ageing rate remain largely unknown. Here, we characterise genome-wide expression patterns of a long-lived, natural variant of Drosophila melanogaster resulting from selection for starvation resistance (SR and compare it with normal-lived control flies (C. We do this at two time points representing middle age (90% survival and old age (10% survival respectively, in three adult diets (malnutrition, optimal food, and overfeeding. Results We found profound differences between Drosophila lines in their age-related expression. Most of the age-associated changes in normal-lived flies were abrogated in long-lived Drosophila. The stress-related genes, including those involved in proteolysis and cytochrome P450, were generally higher expressed in SR flies and showed a smaller increase in expression with age compared to C flies. The genes involved in reproduction showed a lower expression in middle-aged SR than in C flies and, unlike C flies, a lack of their downregulation with age. Further, we found that malnutrition strongly affected age-associated transcript patterns overriding the differences between the lines. However, under less stressful dietary conditions, line and diet affected age-dependent expression similarly. Finally, we present lists of candidate markers of ageing and lifespan extension. Conclusions Our study unveils transcriptional changes associated with lifespan extension in SR Drosophila. The results suggest that natural genetic variation for SR and lifespan can operate through similar transcriptional mechanisms as those of dietary restriction and life-extending mutations.

  8. Loss of Ceramide Synthases Elicits a PHA-4/FoxA-, SKN-1-, and Autophagy-Dependent Lifespan Extension in C. elegans

    DEFF Research Database (Denmark)

    Jensen, Mai-Britt Mosbech; Færgeman, Nils J.; Ejsing, Christer S.

    2011-01-01

    , these lipid species are recognized as bioactive signalling molecules involved in regulation of cell growth, differentiation, senescence, and apoptosis, and thus a delicate equilibrium between the levels of these interconvertible lipid species underlies the balance between cell survival and death. The C....... elegans genome comprises three ceramide synthase genes; hyl-1, hyl-2, and lagr-1. Here we show that functional loss of HYL-1 and LAGR-1 depletes 43:1;3 sphingolipids and extends lifespan in a PHA-4-, SKN-1-, and ATG-12-dependent manner. The transcription factors PHA-4 and SKN-1 as well as ATG-12, which...

  9. Analysis of combination drug therapy to develop regimens with shortened duration of treatment for tuberculosis.

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    George L Drusano

    Full Text Available Tuberculosis remains a worldwide problem, particularly with the advent of multi-drug resistance. Shortening therapy duration for Mycobacterium tuberculosis is a major goal, requiring generation of optimal kill rate and resistance-suppression. Combination therapy is required to attain the goal of shorter therapy.Our objective was to identify a method for identifying optimal combination chemotherapy. We developed a mathematical model for attaining this end. This is accomplished by identifying drug effect interaction (synergy, additivity, antagonism for susceptible organisms and subpopulations resistant to each drug in the combination.We studied the combination of linezolid plus rifampin in our hollow fiber infection model. We generated a fully parametric drug effect interaction mathematical model. The results were subjected to Monte Carlo simulation to extend the findings to a population of patients by accounting for between-patient variability in drug pharmacokinetics.All monotherapy allowed emergence of resistance over the first two weeks of the experiment. In combination, the interaction was additive for each population (susceptible and resistant. For a 600 mg/600 mg daily regimen of linezolid plus rifampin, we demonstrated that >50% of simulated subjects had eradicated the susceptible population by day 27 with the remaining organisms resistant to one or the other drug. Only 4% of patients had complete organism eradication by experiment end.These data strongly suggest that in order to achieve the goal of shortening therapy, the original regimen may need to be changed at one month to a regimen of two completely new agents with resistance mechanisms independent of the initial regimen. This hypothesis which arose from the analysis is immediately testable in a clinical trial.

  10. The extended arm of health professionals?

    DEFF Research Database (Denmark)

    Norlyk, Annelise; Martinsen, Bente

    2013-01-01

    responsibility for both the patient's well-being and for the patient's compliance with the daily regimen. Relatives were caught in a conflicting double role. They were the extended arm of the health professionals but also the caring, supporting partner. A tension arose between relatives' desire to help....... Due to the early discharge and the increasing demands on patients for self-care, patients' relatives seem to play a pivotal role in fast-track programmes. However, research is limited into how patients' close relatives are affected by and involved in the postoperative recovery process. Design...

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

    Directory of Open Access Journals (Sweden)

    Alice F. Tarantal

    2014-04-01

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

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

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    Siu Sylvia Lee

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

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

    Science.gov (United States)

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

    2016-01-01

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

  14. An epigenetic biomarker of aging for lifespan and healthspan

    Science.gov (United States)

    Levine, Morgan E.; Lu, Ake T.; Quach, Austin; Chen, Brian H.; Assimes, Themistocles L.; Bandinelli, Stefania; Hou, Lifang; Baccarelli, Andrea A.; Stewart, James D.; Li, Yun; Whitsel, Eric A.; Wilson, James G; Reiner, Alex P; Aviv, Abraham; Lohman, Kurt; Liu, Yongmei; Ferrucci, Luigi

    2018-01-01

    Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging. PMID:29676998

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

    Science.gov (United States)

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

    2017-08-01

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

  16. Age structure changes and extraordinary lifespan in wild medfly populations.

    Science.gov (United States)

    Carey, James R; Papadopoulos, Nikos T; Müller, Hans-Georg; Katsoyannos, Byron I; Kouloussis, Nikos A; Wang, Jane-Ling; Wachter, Kenneth; Yu, Wei; Liedo, Pablo

    2008-06-01

    The main purpose of this study was to test the hypotheses that major changes in age structure occur in wild populations of the Mediterranean fruit fly (medfly) and that a substantial fraction of individuals survive to middle age and beyond (> 3-4 weeks). We thus brought reference life tables and deconvolution models to bear on medfly mortality data gathered from a 3-year study of field-captured individuals that were monitored in the laboratory. The average time-to-death of captured females differed between sampling dates by 23.9, 22.7, and 37.0 days in the 2003, 2004, and 2005 field seasons, respectively. These shifts in average times-to-death provided evidence of changes in population age structure. Estimates indicated that middle-aged medflies (> 30 days) were common in the population. A surprise in the study was the extraordinary longevity observed in field-captured medflies. For example, 19 captured females but no reference females survived in the laboratory for 140 days or more, and 6 captured but no reference males survived in the laboratory for 170 days or more. This paper advances the study of aging in the wild by introducing a new method for estimating age structure in insect populations, demonstrating that major changes in age structure occur in field populations of insects, showing that middle-aged individuals are common in the wild, and revealing the extraordinary lifespans of wild-caught individuals due to their early life experience in the field.

  17. Cognitive Predictors of Everyday Problem Solving across the Lifespan.

    Science.gov (United States)

    Chen, Xi; Hertzog, Christopher; Park, Denise C

    2017-01-01

    An important aspect of successful aging is maintaining the ability to solve everyday problems encountered in daily life. The limited evidence today suggests that everyday problem solving ability increases from young adulthood to middle age, but decreases in older age. The present study examined age differences in the relative contributions of fluid and crystallized abilities to solving problems on the Everyday Problems Test (EPT). We hypothesized that due to diminishing fluid resources available with advanced age, crystallized knowledge would become increasingly important in predicting everyday problem solving with greater age. Two hundred and twenty-one healthy adults from the Dallas Lifespan Brain Study, aged 24-93 years, completed a cognitive battery that included measures of fluid ability (i.e., processing speed, working memory, inductive reasoning) and crystallized ability (i.e., multiple measures of vocabulary). These measures were used to predict performance on EPT. Everyday problem solving showed an increase in performance from young to early middle age, with performance beginning to decrease at about age of 50 years. As hypothesized, fluid ability was the primary predictor of performance on everyday problem solving for young adults, but with increasing age, crystallized ability became the dominant predictor. This study provides evidence that everyday problem solving ability differs with age, and, more importantly, that the processes underlying it differ with age as well. The findings indicate that older adults increasingly rely on knowledge to support everyday problem solving, whereas young adults rely almost exclusively on fluid intelligence. © 2017 S. Karger AG, Basel.

  18. Developmental aspects of synaesthesia across the adult lifespan

    Directory of Open Access Journals (Sweden)

    Beat eMeier

    2014-03-01

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

  19. Genital lesions: An indication for changing ART regimen.

    Science.gov (United States)

    Kumar, S Arun; Kumar, N; Kumarasamy, N

    2011-01-01

    Genital lesions are common in HIV positive patients and aetiology for these are mainly due to HSV, HPV or bacterial. They usually respond to HAART, antiviral or antimicrobials. We are presenting a young patient on HAART with non-healing genital ulcer lesions for sixteen months. He responded well to a change in ART regimen within a period of 15 days. This happened after a change to a more potent ART regimen.

  20. A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice.

    Science.gov (United States)

    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.

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

    CSIR Research Space (South Africa)

    Musee, N

    2012-05-01

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

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

    DEFF Research Database (Denmark)

    Marsh, Rob

    2017-01-01

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

  3. Alcohol Use and Abuse: Understanding Alcohol Use Across Your Lifespan | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Alcohol Use and Abuse Understanding Alcohol Use Across Your Lifespan Past Issues / Winter 2013 Table of Contents Alcohol use and the risk for alcohol-related problems ...

  4. Association between duration of reproductive lifespan and Framingham risk score in postmenopausal women.

    Science.gov (United States)

    Kim, Soo Hyun; Sim, Mu Yul; Park, Sat Byul

    2015-12-01

    The benefit of estrogen therapy in postmenopausal women is still uncertain. Based upon extensive observational data, it was believed that estrogen was cardioprotective. The relationship between the period of exposure to endogenous estrogens and the risk of cardiovascular disease (CVD) has not been studied in Korean women. To assess associations between reproductive lifespan and CVD by using the Framingham risk score (FRS) in postmenopausal Korean women. This cross-sectional, population-based study used data from the Korea National Health and Nutrition Examination Survey (KNHANES) for the five years 2008-2012,after adjustment for relevant variables using complex sample analysis and data weighting. Among 25,534 women, 1973 women were enrolled, after excluding those 80 years of age (n=6194), those with diabetes, CVD or cancer (n=491), those with unrecorded physical measurements (n=7335), those with menarche age ≤8 years or ≥20 years (n=6194), and premenopausal women (n=3347). The FRS tended to show a significant negative correlation with the reproductive lifespan (preproductive lifespan and FRS (adjusted relative risk [RR] for reproductive years [shortest lifespan group] compared with 28-33 reproductive years [moderate lifespan group], 1.2, p33 reproductive years [longest lifespan group] compared with 28-33 reproductive years [moderate lifespan group], -0.42, p=0.011). A longer reproductive lifespan is associated with a lower estimated risk of CVD in the next 10 years in postmenopausal women. This result suggests that estrogen has a long-term protective effect against CVD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Effect of gamma irradiation on lifespan and offspring physiology of male drosophila melanogaster

    International Nuclear Information System (INIS)

    Hou Jiangyu; Gu Wei; Jiang Fangping; Han Hetong

    2010-01-01

    This study aimed to investigate the effects of γ-rays irradiation on adult longevity and physiological changes in F 1 generation.Male Drosophila melanogaster at 1 ∼ 2 days old were irradiated by γ-rays with doses of 5, 10, 15 and 30 Gy. In all experimental groups, mean lifespan, maximum lifespan and 90% of lethaldeath irradiated flies were reduced(at P 1 generation of irradiated group, body weight increased, but the capacity of physiological stress declined. (authors)

  6. Uneven Futures of Human Lifespans: Reckonings from Gompertz Mortality Rates, Climate Change, and Air Pollution

    OpenAIRE

    Finch, Caleb E; Beltrán-Sánchez, Hiram; Crimmins, Eileen M

    2013-01-01

    The past 200 years have enabled remarkable increases in human lifespans through improvements in the living environment that have nearly eliminated infections as a cause of death through improved hygiene, public health, medicine, and nutrition. We argue that the limit to lifespan may be approaching. Since 1997, no one has exceeded Jeanne Calment's record of 122.5 years, despite an exponential increase of centenarians. Moreover, the background mortality may be approaching a lower limit. We calc...

  7. Parametric and non-parametric models for lifespan modeling of insulation systems in electrical machines

    OpenAIRE

    Salameh , Farah; Picot , Antoine; Chabert , Marie; Maussion , Pascal

    2017-01-01

    International audience; This paper describes an original statistical approach for the lifespan modeling of electric machine insulation materials. The presented models aim to study the effect of three main stress factors (voltage, frequency and temperature) and their interactions on the insulation lifespan. The proposed methodology is applied to two different insulation materials tested in partial discharge regime. Accelerated ageing tests are organized according to experimental optimization m...

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

    Directory of Open Access Journals (Sweden)

    Hans B Sieburg

    2013-04-01

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

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

    DEFF Research Database (Denmark)

    Jouvet, Lionel; Steiner, Ulrich

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

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

    Directory of Open Access Journals (Sweden)

    Jitendra Kumar

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

  11. Toward an understanding of late life suicidal behavior: the role of lifespan developmental theory.

    Science.gov (United States)

    Fiske, Amy; O'Riley, Alisa A

    2016-01-01

    Suicidal behavior in late life differs in important ways from suicidal behavior that occurs earlier in the lifespan, suggesting the possibility of developmental differences in the etiology of suicidal behavior. This paper examines late life suicidal behavior within the context of lifespan developmental theory. This paper presents a conceptual framework for using lifespan developmental theory to better understand late life suicidal behavior. We argue that the motivational theory of lifespan development, which focuses on control, is particularly relevant to late life suicide. This theory posits that opportunities to exert control over important aspects of one's life diminish in late life as a result of declines in physical functioning and other factors, and that successful aging is associated with adaptive regulation of this developmental change. Although continued striving to meet goals is normative throughout the lifespan, most individuals also increase the use of compensatory strategies in old age or when faced with a decline in functioning. We propose that individuals who do not adapt to developmental changes by altering their strategies for exerting control will be at risk for suicidal behavior in late life. This paper reviews evidence that supports the importance of control with respect to suicidal outcomes in older adults, as well as findings regarding specific types of control strategies that may be related to suicide risk in older adults with health-related limitations. Although suicidal behavior is not a normal part of aging, the application of lifespan developmental theory may be useful in understanding and potentially preventing suicide among older adults.

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

    Science.gov (United States)

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

    2016-01-01

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

  13. Extended and continuous use of hormonal contraceptives to reduce menstruation.

    Science.gov (United States)

    Wiegratz, Inka; Kissler, Stefan; Kuhl, Herbert; Kaufmann, Manfred

    2006-09-01

    During the use of long-cycle regimens of monophasic oral contraceptives, the total number of bleeding and cycle-dependent complaints is considerably lower than during conventional treatment with oral contraceptives. Despite an initially higher rate of irregular bleeding, the majority of women prefer the long-cycle treatment since it may improve quality of life. As this regimen provides an enhanced ovarian suppression, it may prevent pregnancies, especially in noncompliant women or patients who are concomitantly treated with drugs that may impair the efficacy of oral contraceptives. Postponement or suppression of withdrawal bleeding also reduces menses-associated disorders such as menorrhagia and dysmenorrhea, and has beneficial effects in patients with hemorrhagic diathesis, endometriosis, uterine leiomyomas and polycystic ovary syndrome. Long-term studies are necessary to assess the impact of long-term use of extended regimens of oral contraceptives on safety, for example, the risk of cancer and cardiovascular disease, and on fertility after discontinuation of treatment.

  14. Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan

    Directory of Open Access Journals (Sweden)

    Tuan Leng Tay

    2018-01-01

    Full Text Available Microglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance, and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD, hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs, and obsessive-compulsive disorder (OCD or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD, bipolar disorder (BD, schizophrenia, eating disorders and sleep disorders. Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer’s and Parkinson’s. Taking into account the recent identification of

  15. Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan.

    Science.gov (United States)

    Tay, Tuan Leng; Béchade, Catherine; D'Andrea, Ivana; St-Pierre, Marie-Kim; Henry, Mathilde S; Roumier, Anne; Tremblay, Marie-Eve

    2017-01-01

    Microglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS) that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance), and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD), hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs), and obsessive-compulsive disorder (OCD)) or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, eating disorders and sleep disorders). Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer's and Parkinson's). Taking into account the recent identification of microglia

  16. Lifespan anxiety is reflected in human amygdala cortical connectivity

    Science.gov (United States)

    He, Ye; Xu, Ting; Zhang, Wei

    2016-01-01

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

  17. How Far Can Extended Knowledge Be Extended?

    DEFF Research Database (Denmark)

    Wray, K. Brad

    2018-01-01

    by an artifact, like a notebook or telescope. The chapter illustrates this by applying Pritchard’s account of extended knowledge to collaborating scientists. The beliefs acquired through collaborative research cannot satisfy both of Pritchard’s conditions of creditability. Further, there is evidence......Duncan Pritchard (2010) has developed a theory of extended knowledge based on the notion of extended cognition initially developed by Clark and Chalmers (1998). Pritchard’s account gives a central role to the notion of creditability, which requires the following two conditions to be met: (i...... that scientists are not prepared to take responsibility for the actions of the scientists with whom they collaborate....

  18. Hypofractionation Regimens for Stereotactic Radiotherapy for Large Brain Tumors

    International Nuclear Information System (INIS)

    Yuan Jiankui; Wang, Jian Z.; Lo, Simon; Grecula, John C.; Ammirati, Mario; Montebello, Joseph F.; Zhang Hualin; Gupta, Nilendu; Yuh, William T.C.; Mayr, Nina A.

    2008-01-01

    Purpose: To investigate equivalent regimens for hypofractionated stereotactic radiotherapy (HSRT) for brain tumor treatment and to provide dose-escalation guidance to maximize the tumor control within the normal brain tolerance. Methods and Materials: The linear-quadratic model, including the effect of nonuniform dose distributions, was used to evaluate the HSRT regimens. The α/β ratio was estimated using the Gammaknife stereotactic radiosurgery (GKSRS) and whole-brain radiotherapy experience for large brain tumors. The HSRT regimens were derived using two methods: (1) an equivalent tumor control approach, which matches the whole-brain radiotherapy experience for many fractions and merges it with the GKSRS data for few fractions; and (2) a normal-tissue tolerance approach, which takes advantages of the dose conformity and fractionation of HSRT to approach the maximal dose tolerance of the normal brain. Results: A plausible α/β ratio of 12 Gy for brain tumor and a volume parameter n of 0.23 for normal brain were derived from the GKSRS and whole-brain radiotherapy data. The HSRT prescription regimens for the isoeffect of tumor irradiation were calculated. The normal-brain equivalent uniform dose decreased as the number of fractions increased, because of the advantage of fractionation. The regimens for potential dose escalation of HSRT within the limits of normal-brain tolerance were derived. Conclusions: The designed hypofractionated regimens could be used as a preliminary guide for HSRT dose prescription for large brain tumors to mimic the GKSRS experience and for dose escalation trials. Clinical studies are necessary to further tune the model parameters and validate these regimens

  19. Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Simonsen, Janne Lytoft; Rosada, Cecilia; Serakinci, Nedime

    2002-01-01

    Human bone marrow stromal cells (hMSCs) were stably transduced by a retroviral vector containing the gene for the catalytic subunit of human telomerase (hTERT). Transduced cells (hMSC-TERTs) had telomerase activity, and the mean telomere length was increased as compared with that of control cells....... The transduced cells have now undergone more than 260 population doublings (PD) and continue to proliferate, whereas control cells underwent senescence-associated proliferation arrest after 26 PD. The cells maintained production of osteoblastic markers and differentiation potential during continuous subculturing......, did not form tumors, and had a normal karyotype. When implanted subcutaneously in immunodeficient mice, the transduced cells formed more bone than did normal cells. These results suggest that ectopic expression of telomerase in hMSCs prevents senescence-associated impairment of osteoblast functions....

  20. Extended Enterprise performance Management

    NARCIS (Netherlands)

    Bobbink, Maria Lammerdina; Hartmann, Andreas

    2014-01-01

    The allegiance of partnering organisations and their employees to an Extended Enterprise performance is its proverbial sword of Damocles. Literature on Extended Enterprises focuses on collaboration, inter-organizational integration and learning to avoid diminishing or missing allegiance becoming an

  1. Life-span studies of inhaled plutonium in beagle dogs

    International Nuclear Information System (INIS)

    Bair, W.J.

    1991-01-01

    In 1970 a life-span study with over 300 beagle dogs was begun. Groups of beagle dogs were given single exposures to 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 to obtain graded levels of initial lung burdens ranging from 1 to 1800 Bq lung. After 16 years, the lungs contained about 2% of the initial lung burden of 239 PuO 2 , the thoracic lymph nodes 20%, skeleton 1% and liver 10%. After 15 years the lungs contained about 0.2% of the initial lung burden of 238 PuO 2 , thoracic lymph nodes 5%, skeleton 10%, and liver 10%. After 10 years the lungs contained about 0.29% of the initial lung burden of 239 Pu(NO 3 ) 4 , thoracic lymph nodes 0.17%, skeleton 18% and liver 13%. Chronic lymphopenia has been one of the earliest biological effects observed. Other effects associated with plutonium exposure included sclerosis of the tracheobronchial lymph nodes, focal radiation pneumonitis, adenomatous hyperplasia of the liver and dystrophic osteolytic lesions in the skeleton. In 16 years, mortality due to radiation pneumonitis and/or lung tumor increased with deposition of 24 Bq of 239 PuO 2 . In 15 years, mortality due to lung and/or bone tumors increased with deposition of 96 Bq of 238 PuO 2 . In 11 years, after exposure, mortality due to lung and/or bone tumors increased with deposition of 18 Bq of 239 Pu(NO 3 ) 4 . Lung cancers appeared to originate in the parenchymal regions of the lungs and were of several types; bronchiolar alveolar carcinoma, papillary adenocarcinomas, adenosquamous carcinoma, and epidermoid carcinoma. Metastases were primarily to the thoracic lymph nodes. Sites of osteosarcomas in the 238 PuO 2 and 239 Pu(NO 3 ) 4 dogs were in the lumbar cervical and thoracic vertebrae, humerus, pelvis, facial bones, ribs and nasal turbinates. The risk of lung cancer, based on cumulative dose to the lungs, was about 12 times higher for 239 Pu(NO 3 ) 4 than from inhaled 239 PuO 2 , and 50 times higher than for inhaled 238 PuO 2 . (J.P.N.)

  2. Perspectives on extended Deterrence

    International Nuclear Information System (INIS)

    Tertrais, Bruno; Yost, David S.; Bunn, Elaine; Lee, Seok-soo; Levite, Ariel e.; Russell, James A.; Hokayem, Emile; Kibaroglu, Mustafa; Schulte, Paul; Thraenert, Oliver; Kulesa, Lukasz

    2010-05-01

    In November 2009, the Foundation for Strategic Research (Fondation pour la recherche strategique, FRS) convened a workshop on 'The Future of extended Deterrence', which included the participation of some of the best experts of this topic, from the United States, Europe, the Middle East and East Asia, as well as French and NATO officials. This document brings together the papers prepared for this seminar. Several of them were updated after the publication in April 2010 of the US Nuclear Posture Review. The seminar was organized with the support of the French Atomic energy Commission (Commissariat a l'energie atomique - CEA). Content: 1 - The future of extended deterrence: a brainstorming paper (Bruno Tertrais); 2 - US extended deterrence in NATO and North-East Asia (David S. Yost); 3 - The future of US extended deterrence (Elaine Bunn); 4 - The future of extended deterrence: a South Korean perspective (Seok-soo Lee); 5 - Reflections on extended deterrence in the Middle East (Ariel e. Levite); 6 - extended deterrence, security guarantees and nuclear weapons: US strategic and policy conundrums in the Gulf (James A. Russell); 7 - extended deterrence in the Gulf: a bridge too far? (Emile Hokayem); 8 - The future of extended deterrence: the case of Turkey (Mustafa Kibaroglu); 9 - The future of extended deterrence: a UK view (Paul Schulte); 10 - NATO and extended deterrence (Oliver Thraenert); 11 - extended deterrence and assurance in Central Europe (Lukasz Kulesa)

  3. Characteristics of HIV antiretroviral regimen and treatment adherence

    Directory of Open Access Journals (Sweden)

    Vera Lúcia da Silveira

    Full Text Available The relationship between characteristics of HIV antiretroviral regimens and treatment adherence was studied in adolescent and adult patients who underwent antiretroviral therapy from January 1998 to September 2000, at the Service for Specialized Assistance in Pelotas. The patients were interviewed on two occasions, and the use of antiretrovirals during the previous 48 hours was investigated by a self-report. Adherence was defined as use of 95% or more of the prescribed medication. Social-demographic variables were collected through direct questionnaires. The antiretroviral regimen and clinical data were copied from the patients' records. Associations between the independent variables and adherence were analyzed by means of logistic regression. The multivariate analysis included characteristics of the antiretroviral regimens, social-demographic variables, as well as perception of negative effects, negative physiological states, and adverse effects of the treatment. Among the 224 selected patients, 194 participated in our study. Their ages varied from 17 to 67 years; most patients were men, with few years of schooling and a low family income. Only 49% adhered to the treatment. Adherence to treatment regimens was reduced when more daily doses were indicated: three to four doses (odds ratio of adherence to treatment (OR=0.47, 95% confidence interval (CI 0.22-1.01 and five to six (OR=0.24, 95% CI 0.09-0.62; two or more doses taken in a fasting state (OR=0.59, 95% CI 0.11-0.68, and for patients who reported adverse effects to the treatment (OR=0.39, 95% CI 0.19-0.77. Most of the regimens with more than two daily doses of medication included at least one dose apart from mealtimes. The results suggest that, if possible, regimens with a reduced number of doses should be chosen, with no compulsory fasting, and with few adverse effects. Strategies to minimize these effects should be discussed with the patients.

  4. Zagreb regimen, an abbreviated intramuscular schedule for rabies vaccination.

    Science.gov (United States)

    Ren, Jiangping; Yao, Linong; Sun, Jimin; Gong, Zhenyu

    2015-01-01

    The Zagreb regimen, an abbreviated intramuscular schedule for rabies vaccination, was developed by I. Vodopija and colleagues of the Zagreb Institute of Public Health in Croatia in the 1980s. It was recommended by WHO as one of the intramuscular (IM) schedules for rabies vaccination in 2010. We reviewed the literature on the immunogenicity, safety, economic burden, and compliance of the Zagreb 2-1-1 regimen. Compared to Essen, another IM schedule recommended by WHO, Zagreb has higher compliance, lower medical cost, and better immunogenicity at an early stage. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. Eruptive furunculosis following the soak and smear regimen.

    Science.gov (United States)

    Martires, Kathryn; Sukhdeo, Kumar; Meinhardt, Eric

    2015-02-18

    The 'soak and smear' regimen is a highly effective method for localised topical therapy employed by dermatologists for widespread inflammatory skin conditions. The regimen involves application of topical medication under occlusion after soaking in water. Complications from this treatment method are rare. We present a case of multiple, generalised methicillin-resistant Staphylococcus aureus (MRSA)-positive furuncles arising in a patient as an unexpected consequence of therapy. The case highlights an unanticipated risk of a commonly employed treatment amid an epidemic of MRSA in the community. 2015 BMJ Publishing Group Ltd.

  6. The sensory system acts with a neuromedin U signaling pathway to mediate food type-dependent effects on lifespan

    OpenAIRE

    Adilov, Bakhtiyor

    2010-01-01

    In order to survive, the animal uses its sensory system to interpret the complexity of its environment. Interestingly, a subset of sensory neurons, which function in taste or olfaction, has been found to influence the lifespan of C. elegans and Drosophila. Although the mechanisms by which these neurons affect lifespan are unknown, the nature of these neurons suggest that the sensory influence on lifespan is mediated by food-derived cues. This thesis shows that sensory neurons r...

  7. Bacillus subtilis biofilm extends Caenorhabditis elegans longevity through downregulation of the insulin-like signalling pathway

    Science.gov (United States)

    Donato, Verónica; Ayala, Facundo Rodríguez; Cogliati, Sebastián; Bauman, Carlos; Costa, Juan Gabriel; Leñini, Cecilia; Grau, Roberto

    2017-01-01

    Beneficial bacteria have been shown to affect host longevity, but the molecular mechanisms mediating such effects remain largely unclear. Here we show that formation of Bacillus subtilis biofilms increases Caenorhabditis elegans lifespan. Biofilm-proficient B. subtilis colonizes the C. elegans gut and extends worm lifespan more than biofilm-deficient isogenic strains. Two molecules produced by B. subtilis — the quorum-sensing pentapeptide CSF and nitric oxide (NO) — are sufficient to extend C. elegans longevity. When B. subtilis is cultured under biofilm-supporting conditions, the synthesis of NO and CSF is increased in comparison with their production under planktonic growth conditions. We further show that the prolongevity effect of B. subtilis biofilms depends on the DAF-2/DAF-16/HSF-1 signalling axis and the downregulation of the insulin-like signalling (ILS) pathway. PMID:28134244

  8. Icariin and its derivative icariside II extend healthspan via insulin/IGF-1 pathway in C. elegans.

    Directory of Open Access Journals (Sweden)

    Wai-Jiao Cai

    Full Text Available Compounds that delay aging might also postpone age-related diseases and extend healthspan in humans. Icariin is a flavonol extracted from several plant species of the Epimedium family. The icariin and its metabolic derivatives have been shown to exert wide protective effects in age-related diseases. However, whether icariin and its derivatives have the potency of delaying aging remains unclear. Here, we report that icariin and its derivative icariside II extend C. elegans lifespan. Using HPLC, we found high level of icariside II in the animals treated with icariin, suggesting icariside II is the bioactive form in vivo of icariin. Icariside II also increased the thermo and oxidative stress tolerance, slowed locomotion decline in late adulthood and delayed the onset of paralysis mediated by polyQ and Aβ(1-42 proteotoxicity. The lifespan extension effect of icariside II is dependent on the insulin/IGF-1 signaling (IIS since the daf-16(mu86 and daf-2(e1370 failed to show any lifespan extension upon icariside II treatment. Consistently, icariside II treatment upregulates the expression of DAF-16 targets in the wild-type. Moreover, our data suggests that the heat shock transcription factor HSF-1 has a role in icariside II-dependent lifespan extension further implicating the IIS pathway. In conclusion, we demonstrate a novel natural compound, icariside II as the bioactive form of icariin, extends the healthspan via IIS pathway in C. elegans.

  9. Reward speeds up and increases consistency of visual selective attention: a lifespan comparison.

    Science.gov (United States)

    Störmer, Viola; Eppinger, Ben; Li, Shu-Chen

    2014-06-01

    Children and older adults often show less favorable reward-based learning and decision making, relative to younger adults. It is unknown, however, whether reward-based processes that influence relatively early perceptual and attentional processes show similar lifespan differences. In this study, we investigated whether stimulus-reward associations affect selective visual attention differently across the human lifespan. Children, adolescents, younger adults, and older adults performed a visual search task in which the target colors were associated with either high or low monetary rewards. We discovered that high reward value speeded up response times across all four age groups, indicating that reward modulates attentional selection across the lifespan. This speed-up in response time was largest in younger adults, relative to the other three age groups. Furthermore, only younger adults benefited from high reward value in increasing response consistency (i.e., reduction of trial-by-trial reaction time variability). Our findings suggest that reward-based modulations of relatively early and implicit perceptual and attentional processes are operative across the lifespan, and the effects appear to be greater in adulthood. The age-specific effect of reward on reducing intraindividual response variability in younger adults likely reflects mechanisms underlying the development and aging of reward processing, such as lifespan age differences in the efficacy of dopaminergic modulation. Overall, the present results indicate that reward shapes visual perception across different age groups by biasing attention to motivationally salient events.

  10. Regional and longitudinal estimation of product lifespan distribution: a case study for automobiles and a simplified estimation method.

    Science.gov (United States)

    Oguchi, Masahiro; Fuse, Masaaki

    2015-02-03

    Product lifespan estimates are important information for understanding progress toward sustainable consumption and estimating the stocks and end-of-life flows of products. Publications reported actual lifespan of products; however, quantitative data are still limited for many countries and years. This study presents regional and longitudinal estimation of lifespan distribution of consumer durables, taking passenger cars as an example, and proposes a simplified method for estimating product lifespan distribution. We estimated lifespan distribution parameters for 17 countries based on the age profile of in-use cars. Sensitivity analysis demonstrated that the shape parameter of the lifespan distribution can be replaced by a constant value for all the countries and years. This enabled a simplified estimation that does not require detailed data on the age profile. Applying the simplified method, we estimated the trend in average lifespans of passenger cars from 2000 to 2009 for 20 countries. Average lifespan differed greatly between countries (9-23 years) and was increasing in many countries. This suggests consumer behavior differs greatly among countries and has changed over time, even in developed countries. The results suggest that inappropriate assumptions of average lifespan may cause significant inaccuracy in estimating the stocks and end-of-life flows of products.

  11. Relieving Pain using Dose-Extending Placebos: A Scoping Review

    Science.gov (United States)

    Colloca, Luana; Enck, Paul; DeGrazia, David

    2017-01-01

    Placebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with their typical current use, a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects. Is it possible to extend the effects of drug treatments by interspersing placebos? We reviewed a database of placebo studies, searching for studies that indicate that placebos given after repeated administration of active treatments acquire medication-like effects. We found a total of 22studies in both animals and humans hinting of evidence that placebos may work as a sort of dose extender of active painkillers. Wherever effective in relieving clinical pain, such placebo use would offer several advantages. First, extending the effects of a painkiller through the use of placebos may reduce total drug intake and side effects. Second, dose-extending placebos may decrease patient dependence. Third, using placebos along with active medication, for part of the course of treatment, should limit dose escalation and lower costs. Importantly, provided that nondisclosure is pre-authorized in the informed consent process and that robust evidence indicates therapeutic benefit comparable to that of standard full-dose therapeutic regimens, introducing dose-extending placebos into the clinical arsenal should be considered. This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments, the typical regimens of painkiller applications, and the ways in which treatments are evaluated. PMID:27023425

  12. Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

    Directory of Open Access Journals (Sweden)

    Balk JM

    2015-08-01

    Full Text Available Jiska M Balk,1 Guido RMM Haenen,1 Özgür M Koc,2 Ron Peters,3 Aalt Bast,1 Wim JF van der Vijgh,1 Ger H Koek,4 1Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, 2Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 3DSM Resolve, Geleen, 4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: The combination of ribavirin (RBV and pegylated interferon (PEG-IFN is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens. Methods: In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Results: Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose was significantly different between the two groups (P>0.05. Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0

  13. Gonzalez Regimen (PDQ®)—Health Professional Version

    Science.gov (United States)

    The Gonzalez regimen is a specialized diet that uses enzymes, supplements, and other factors in cancer management. It is based on a theory that involves the use of pancreatic enzymes to help the body get rid of toxins that lead to cancer. Read about existing clinical data in this expert-reviewed summary.

  14. What to Start: Selecting a First HIV Regimen

    Science.gov (United States)

    ... CCR5 antagonists Integrase strand transfer inhibitors (INSTIs) Post-attachment inhibitors In general, a person's first HIV regimen includes two NRTIs plus an INSTI, an NNRTI, or a PI boosted with cobicistat (brand name: Tybost) or ritonavir (brand name: Norvir). Cobicistat ...

  15. Efficacy of Some Combination Regimens of Oral Hypoglycaemic ...

    African Journals Online (AJOL)

    Purpose: To examine the efficacy of selected oral hypoglycaemic agent (OHA) regimens in a small group of patients receiving such treatment. Methods: This was a retrospective, observational study that involved patients who had been diagnosed with type 2 diabetes mellitus and undergoing routine follow-up at a teaching ...

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

    Directory of Open Access Journals (Sweden)

    Adam J. Dobson

    2017-01-01

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

  17. The Effect of Post-Reproductive Lifespan on the Fixation Probability of Beneficial Mutations

    DEFF Research Database (Denmark)

    Giaimo, Stefano; Baudisch, Annette

    2015-01-01

    Post-reproductive lifespan is a common trait among mammals and is usually considered to be neutral; i.e. with no influence on population dynamics. Here, we explore the role of post-reproductive lifespan in the fixation probability of beneficial genetic variation. We compare two separate, stationary...... populations living in a constant environment that are equivalent except for the average time their respective members spend in the post-reproductive stage of life. Using a recently derived approximation, we show that fixation of a beneficial mutation is more likely in the population with greater post......-reproductive longevity. This finding is surprising, as the population with more prolonged post-reproductive lifespan has smaller effective size and the classic population-genetic model would suggest that decreasing effective size reduces fixation chances of beneficial mutations. Yet, as we explain, in the age...

  18. IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan.

    Science.gov (United States)

    Ashpole, Nicole M; Logan, Sreemathi; Yabluchanskiy, Andriy; Mitschelen, Matthew C; Yan, Han; Farley, Julie A; Hodges, Erik L; Ungvari, Zoltan; Csiszar, Anna; Chen, Sixia; Georgescu, Constantin; Hubbard, Gene B; Ikeno, Yuji; Sonntag, William E

    2017-04-01

    Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging mechanism that contributes to increased lifespan in diverse experimental models. However, IGF-1 has also been shown to be essential for normal development and the maintenance of tissue function late into the lifespan. These disparate findings suggest that IGF-1 may be a pleiotropic modulator of health and aging, as reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental for another. We postulated that the effects of IGF-1 on tissue health and function in advanced age are dependent on the tissue, the sex of the animal, and the age at which IGF-1 is manipulated. In this study, we examined how alterations in IGF-1 levels at multiple stages of development and aging influence overall lifespan, healthspan, and pathology. Specifically, we investigated the effects of perinatal, post-pubertal, and late-adult onset IGF-1 deficiency using genetic and viral approaches in both male and female igf f/f C57Bl/6 mice. Our results support the concept that IGF-1 levels early during lifespan establish the conditions necessary for subsequent healthspan and pathological changes that contribute to aging. Nevertheless, these changes are specific for each sex and tissue. Importantly, late-life IGF-1 deficiency (a time point relevant for human studies) reduces cancer risk but does not increase lifespan. Overall, our results indicate that the levels of IGF-1 during development influence late-life pathology, suggesting that IGF-1 is a developmental driver of healthspan, pathology, and lifespan.

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

    Directory of Open Access Journals (Sweden)

    Yong-Jian Ma

    2016-01-01

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

  20. Alternative temozolomide dosing regimens and novel combinations for the treatment of advanced metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Wen-Jen Hwu

    2011-12-01

    Full Text Available Over the past 30 years, there has been no significant improvement in treatment outcomes for patients with advanced stage IV metastatic melanoma, and prognosis remains poor. Melanoma is known to be responsive to immunomodulatory agents, to be a highly vascular tumor, and to be fairly resistant to standard cytotoxic chemotherapy. Ongoing research is attempting to find novel combinations that may have therapeutic synergy. Alternative dosedense schedules of temozolomide appear promising and are being actively investigated, based on their potential to overcome chemoresistance to alkylating agents and the proven activity of temozolomide in the brain. Outcomes of studies investigating single-agent temozolomide suggest that it has activity similar to single-agent dacarbazine. Other studies combining temozolomide with either interferon- alfa or thalidomide suggest that the addition of these immunomodulatory agents to temozolomide improves response rates and may improve overall survival. The best results have been achieved with the extended, daily, dosedense temozolomide regimen. Further research is needed to determine the optimal temozolomide regimen and best combination approach

  1. Aggressive Regimens for Multidrug-Resistant Tuberculosis Reduce Recurrence

    Science.gov (United States)

    Franke, Molly F.; Appleton, Sasha C.; Mitnick, Carole D.; Furin, Jennifer J.; Bayona, Jaime; Chalco, Katiuska; Shin, Sonya; Murray, Megan; Becerra, Mercedes C.

    2013-01-01

    Background. Recurrent tuberculosis disease occurs within 2 years in as few as 1% and as many as 29% of individuals successfully treated for multidrug-resistant (MDR) tuberculosis. A better understanding of treatment-related factors associated with an elevated risk of recurrent tuberculosis after cure is urgently needed to optimize MDR tuberculosis therapy. Methods. We conducted a retrospective cohort study among adults successfully treated for MDR tuberculosis in Peru. We used multivariable Cox proportional hazards regression analysis to examine whether receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion from positive to negative was associated with a reduced rate of recurrent tuberculosis. Results. Among 402 patients, the median duration of follow-up was 40.5 months (interquartile range, 21.2–53.4). Receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion was associated with a lower risk of recurrent tuberculosis (hazard ratio, 0.40 [95% confidence interval, 0.17–0.96]; P = .04). A baseline diagnosis of diabetes mellitus also predicted recurrent tuberculosis (hazard ratio, 10.47 [95% confidence interval, 2.17–50.60]; P = .004). Conclusions. Individuals who received an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion experienced a lower rate of recurrence after cure. Efforts to ensure that an aggressive regimen is accessible to all patients with MDR tuberculosis, such as minimization of sequential ineffective regimens, expanded drug access, and development of new MDR tuberculosis compounds, are critical to reducing tuberculosis recurrence in this population. Patients with diabetes mellitus should be carefully managed during initial treatment and followed closely for recurrent disease. PMID:23223591

  2. Fluid regimens for colostomy irrigation: a systematic review.

    Science.gov (United States)

    Lizarondo, Lucylynn; Aye Gyi, Aye; Schultz, Tim

    2008-09-01

    Background  Various techniques for managing faecal evacuation have been proposed; however, colostomy irrigation is favoured as it leads to better patient outcomes. Alternative fluid regimens for colostomy irrigation have been suggested to achieve effective evacuation. Aim  The objective of this review was to summarise the best available evidence on the most effective fluid regimen for colostomy irrigation. Search strategy  Trials were identified by electronic searches of CINAHL, PubMed, MEDLINE, Current Contents, the Cochrane Library and EMBASE. Unpublished articles and references lists from included studies were also searched. Selection criteria  Randomised controlled trials and before-and-after studies investigating any fluid regimen for colostomy irrigation were eligible for inclusion. Outcomes measured included fluid inflow time, total wash-out time, haemodynamic changes during irrigation, cramps, leakage episodes, quality of life and level of satisfaction. Data collection and analysis  Trial selection, quality appraisal and data extraction were carried out independently by two reviewers. Differences in opinion were resolved by discussion. Main results  The systematic literature search strategy identified two cross-over trials that compared water with another fluid regimen. Owing to the differences in irrigating solutions used, the results were not pooled for analysis. Both the polyethylene glycol electrolyte solution and glyceryl trinitrate performed significantly better than water. Conclusion  There is some evidence to support the effectiveness of fluid regimens other than water, such as polyethylene glycol electrolyte and glyceryl trinitrate, for colostomy irrigation. Further well-designed clinical trials are required to establish solid evidence on the effectiveness of other irrigating solutions that might enhance colonic irrigation. © 2008 The Authors. Journal Compilation © Blackwell Publishing Asia Pty Ltd.

  3. Extended icosahedral structures

    CERN Document Server

    Jaric, Marko V

    1989-01-01

    Extended Icosahedral Structures discusses the concepts about crystal structures with extended icosahedral symmetry. This book is organized into six chapters that focus on actual modeling of extended icosahedral crystal structures. This text first presents a tiling approach to the modeling of icosahedral quasiperiodic crystals. It then describes the models for icosahedral alloys based on random connections between icosahedral units, with particular emphasis on diffraction properties. Other chapters examine the glassy structures with only icosahedral orientational order and the extent of tra

  4. Extending Database Integration Technology

    National Research Council Canada - National Science Library

    Buneman, Peter

    1999-01-01

    Formal approaches to the semantics of databases and database languages can have immediate and practical consequences in extending database integration technologies to include a vastly greater range...

  5. Modelling impacts of performance on the probability of reproducing, and thereby on productive lifespan, allow prediction of lifetime efficiency in dairy cows.

    Science.gov (United States)

    Phuong, H N; Blavy, P; Martin, O; Schmidely, P; Friggens, N C

    2016-01-01

    Reproductive success is a key component of lifetime efficiency - which is the ratio of energy in milk (MJ) to energy intake (MJ) over the lifespan, of cows. At the animal level, breeding and feeding management can substantially impact milk yield, body condition and energy balance of cows, which are known as major contributors to reproductive failure in dairy cattle. This study extended an existing lifetime performance model to incorporate the impacts that performance changes due to changing breeding and feeding strategies have on the probability of reproducing and thereby on the productive lifespan, and thus allow the prediction of a cow's lifetime efficiency. The model is dynamic and stochastic, with an individual cow being the unit modelled and one day being the unit of time. To evaluate the model, data from a French study including Holstein and Normande cows fed high-concentrate diets and data from a Scottish study including Holstein cows selected for high and average genetic merit for fat plus protein that were fed high- v. low-concentrate diets were used. Generally, the model consistently simulated productive and reproductive performance of various genotypes of cows across feeding systems. In the French data, the model adequately simulated the reproductive performance of Holsteins but significantly under-predicted that of Normande cows. In the Scottish data, conception to first service was comparably simulated, whereas interval traits were slightly under-predicted. Selection for greater milk production impaired the reproductive performance and lifespan but not lifetime efficiency. The definition of lifetime efficiency used in this model did not include associated costs or herd-level effects. Further works should include such economic indicators to allow more accurate simulation of lifetime profitability in different production scenarios.

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

    Directory of Open Access Journals (Sweden)

    Yuanyuan Li

    2011-02-01

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

  7. Cell Size Influences the Reproductive Potential and Total Lifespan of the Saccharomyces cerevisiae Yeast as Revealed by the Analysis of Polyploid Strains

    Directory of Open Access Journals (Sweden)

    Renata Zadrag-Tecza

    2018-01-01

    Full Text Available The total lifespan of the yeast Saccharomyces cerevisiae may be divided into two phases: the reproductive phase, during which the cell undergoes mitosis cycles to produce successive buds, and the postreproductive phase, which extends from the last division to cell death. These phases may be regulated by a common mechanism or by distinct ones. In this paper, we proposed a more comprehensive approach to reveal the mechanisms that regulate both reproductive potential and total lifespan in cell size context. Our study was based on yeast cells, whose size was determined by increased genome copy number, ranging from haploid to tetraploid. Such experiments enabled us to test the hypertrophy hypothesis, which postulates that excessive size achieved by the cell—the hypertrophy state—is the reason preventing the cell from further proliferation. This hypothesis defines the reproductive potential value as the difference between the maximal size that a cell can reach and the threshold value, which allows a cell to undergo its first cell cycle and the rate of the cell size to increase per generation. Here, we showed that cell size has an important impact on not only the reproductive potential but also the total lifespan of this cell. Moreover, the maximal cell size value, which limits its reproduction capacity, can be regulated by different factors and differs depending on the strain ploidy. The achievement of excessive size by the cell (hypertrophic state may lead to two distinct phenomena: the cessation of reproduction without “mother” cell death and the cessation of reproduction with cell death by bursting, which has not been shown before.

  8. [Russian/German contacts in discussion on cellular mechanisms of aging and lifespan (author's transl)].

    Science.gov (United States)

    Duplenko, J K

    1980-01-01

    This is a brief review of the discussions which took place in natural literature at the end of XIX, and the beginning of XX century concerning the problems of cellular mechanism of aging, animal lifespan, death of metazoa and immortality of protozoa. The participation of German and Russian natural scientists in the discussion of cardinal gerontological questions is specially considered. The close relationship between the gerontological conceptions and the evolutionary ideas is emphasized. The author has established historical continuity of the above conceptions and modern evolutionary approaches to the predetermination of species' lifespan and mechanisms of aging.

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

    Directory of Open Access Journals (Sweden)

    C. L. Hughes

    2015-01-01

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

  10. MODERN BIOTECHNOLOGICAL APPROACHES TO LIFESPAN EXTENSION OF ANIMALS AND HUMANS

    Directory of Open Access Journals (Sweden)

    E. L. Levitsky

    2017-04-01

    Full Text Available The purpose of the research was to analyze current data concerning the problem of extending the life of multicellular animals and humans. The modern views about the processes of aging and prolongation of life are presented. The analysis focused on the genetic mechanisms of aging and mainly biotechnological approaches (genetic engineering, gene therapy, the use of stem cells, and the reprogramming of the genome to prolong the life of multicellular organisms. For comparison, some traditional methods of prolonging life are described (drug therapy, exercise training, calorically restricted nutrition. This analysis allows to postulate the perspectives and advantages of using biotechnological methods for prolonging life in comparison with traditional ones.

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

    Science.gov (United States)

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

    2009-07-01

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

  12. Extended family medicine training

    Science.gov (United States)

    Slade, Steve; Ross, Shelley; Lawrence, Kathrine; Archibald, Douglas; Mackay, Maria Palacios; Oandasan, Ivy F.

    2016-01-01

    Abstract Objective To examine trends in family medicine training at a time when substantial pedagogic change is under way, focusing on factors that relate to extended family medicine training. Design Aggregate-level secondary data analysis based on the Canadian Post-MD Education Registry. Setting Canada. Participants All Canadian citizens and permanent residents who were registered in postgraduate family medicine training programs within Canadian faculties of medicine from 1995 to 2013. Main outcome measures Number and proportion of family medicine residents exiting 2-year and extended (third-year and above) family medicine training programs, as well as the types and numbers of extended training programs offered in 2015. Results The proportion of family medicine trainees pursuing extended training almost doubled during the study period, going from 10.9% in 1995 to 21.1% in 2013. Men and Canadian medical graduates were more likely to take extended family medicine training. Among the 5 most recent family medicine exit cohorts (from 2009 to 2013), 25.9% of men completed extended training programs compared with 18.3% of women, and 23.1% of Canadian medical graduates completed extended training compared with 13.6% of international medical graduates. Family medicine programs vary substantially with respect to the proportion of their trainees who undertake extended training, ranging from a low of 12.3% to a high of 35.1% among trainees exiting from 2011 to 2013. Conclusion New initiatives, such as the Triple C Competency-based Curriculum, CanMEDS–Family Medicine, and Certificates of Added Competence, have emerged as part of family medicine education and credentialing. In acknowledgment of the potential effect of these initiatives, it is important that future research examine how pedagogic change and, in particular, extended training shapes the care family physicians offer their patients. As part of that research it will be important to measure the breadth and uptake of

  13. OASIS 2: online application for survival analysis 2 with features for the analysis of maximal lifespan and healthspan in aging research.

    Science.gov (United States)

    Han, Seong Kyu; Lee, Dongyeop; Lee, Heetak; Kim, Donghyo; Son, Heehwa G; Yang, Jae-Seong; Lee, Seung-Jae V; Kim, Sanguk

    2016-08-30

    Online application for survival analysis (OASIS) has served as a popular and convenient platform for the statistical analysis of various survival data, particularly in the field of aging research. With the recent advances in the fields of aging research that deal with complex survival data, we noticed a need for updates to the current version of OASIS. Here, we report OASIS 2 (http://sbi.postech.ac.kr/oasis2), which provides extended statistical tools for survival data and an enhanced user interface. In particular, OASIS 2 enables the statistical comparison of maximal lifespans, which is potentially useful for determining key factors that limit the lifespan of a population. Furthermore, OASIS 2 provides statistical and graphical tools that compare values in different conditions and times. That feature is useful for comparing age-associated changes in physiological activities, which can be used as indicators of "healthspan." We believe that OASIS 2 will serve as a standard platform for survival analysis with advanced and user-friendly statistical tools for experimental biologists in the field of aging research.

  14. Life-span radiation effects studies in animals: what can they tell us

    International Nuclear Information System (INIS)

    Thompson, R.C.

    1984-05-01

    Results from life-span studies in a variety of animal species have found relatively little application in the development of radiation risk factors for various organs of man. This paper discusses possible reasons for this situation and presents recommendations to correct it

  15. Which HRM practices enhance employee outcomes at work across the life-span?

    NARCIS (Netherlands)

    Veth, Klaske; Korzilius, Hubert P.L.M.; van der Heijden, Beatrice I.J.M.; Emans, Ben; de Lange, Annet H.

    Based on the social exchange theory and on ageing and life-span theories, this paper aims to examine: (1) the relationships between perceived availability and use of HRM practices, and employee outcomes (i.e. work engagement and employability); and (2) how employee age moderates these relationships.

  16. Which HRM practices enhance employee outcomes at work across the life-span?

    NARCIS (Netherlands)

    Veth, K.N.; Korzilius, H.P.L.M.; Heijden, B.I.J.M. van der; Lange, A.H. de; Emans, B.J.M.

    2017-01-01

    Based on the social exchange theory and on ageing and life-span theories, this paper aims to examine: (1) the relationships between perceived availability and use of HRM practices, and employee outcomes (i.e. work engagement and employability); and (2) how employee age moderates these relationships.

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

    Directory of Open Access Journals (Sweden)

    Laurent Kappeler

    2008-10-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  19. Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan

    Science.gov (United States)

    The relationship between lutein and zeaxanthin and visual and cognitive health throughout the lifespan is compelling. There is a variety of evidence to support a role for lutein and zeaxanthin in vision. Lutein's role in cognition has only recently been considered. Lutein and its isomer, zeaxanthin,...

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

    Science.gov (United States)

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

    2011-01-01

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

  1. Age-related differences in cognition across the adult lifespan in autism spectrum disorder

    NARCIS (Netherlands)

    Lever, A.G.; Geurts, H.M.

    It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age-related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is

  2. Weak linear degeneracy and lifespan of classical solutions for first order quasilinear hyperbolic systems

    International Nuclear Information System (INIS)

    Li Tatsien

    1994-01-01

    By means of the concept of the weak linear degeneracy, one gets the global existence and the sharp estimate of the lifespan of C 1 solutions to the Cauchy problem for general first order quasilinear hyperbolic systems with small initial data with compact support. (author). 23 refs, 1 fig

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

    Directory of Open Access Journals (Sweden)

    Virk Bhupinder

    2012-07-01

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

  4. Perceptions of love across the lifespan: differences in passion, intimacy, and commitment

    NARCIS (Netherlands)

    Sumter, S.R.; Valkenburg, P.M.; Peter, J.

    2013-01-01

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

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

    NARCIS (Netherlands)

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

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  7. Gender separation increases somatic growth in females but does not affect lifespan in Nothobranchius furzeri.

    Directory of Open Access Journals (Sweden)

    Michael Graf

    2010-08-01

    Full Text Available According to life history theory, physiological and ecological traits and parameters influence an individual's life history and thus, ultimately, its lifespan. Mating and reproduction are costly activities, and in a variety of model organisms, a negative correlation of longevity and reproductive effort has been demonstrated. We are employing the annual killifish Nothobranchius furzeri as a vertebrate model for ageing. N. furzeri is the vertebrate displaying the shortest known lifespan in captivity with particular strains living only three to four months under optimal laboratory conditions. The animals show explosive growth, early sexual maturation and age-dependent physiological and behavioural decline. Here, we have used N. furzeri to investigate a potential reproduction-longevity trade-off in both sexes by means of gender separation. Though female reproductive effort and offspring investment were significantly reduced after separation, as investigated by analysis of clutch size, eggs in the ovaries and ovary mass, the energetic surplus was not reallocated towards somatic maintenance. In fact, a significant extension of lifespan could not be observed in either sex. This is despite the fact that separated females, but not males, grew significantly larger and heavier than the respective controls. Therefore, it remains elusive whether lifespan of an annual species evolved in periodically vanishing habitats can be prolonged on the cost of reproduction at all.

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

    Directory of Open Access Journals (Sweden)

    Wim Wätjen

    2013-06-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  10. Sexuality and Developmental Disability: Obstacles to Healthy Sexuality throughout the Lifespan

    Science.gov (United States)

    Richards, Deborah; Miodrag, Nancy; Watson, Shelley L.

    2006-01-01

    This paper presents a lifespan perspective of sexuality issues for individuals with developmental disabilities. Individuals with developmental disabilities are human beings who have historically been denied the right to express their sexuality or engage in sexual relationships due to misconceptions or negative attitudes. Using a hypothetical case…

  11. Cognitive Creative Abilities and Self-Esteem across the Adult Life-Span.

    Science.gov (United States)

    Jaquish, Gail A.; Ripple, Richard E.

    1981-01-01

    Explored the relationship between divergent thinking and self-esteem across the adult lifespan. Subjects from 18 to 84 years of age responded to a self-esteem inventory and an exercise in divergent thinking. Self-esteem predicted divergent thinking across age groups, whereas age differences accounted for little variance in divergent thinking.…

  12. Qualitative Exploration of Acculturation and Life-Span Issues of Elderly Asian Americans

    Science.gov (United States)

    Lee, Jee Hyang; Heo, Nanseol; Lu, Junfei; Portman, Tarrell Awe Agahe

    2013-01-01

    Awareness of aging issues across diverse populations begins the journey toward counselors becoming culturally competent across client life spans. Understanding the life-span experiences of cultural groups is important for helping professionals. The purpose of this research was to gain insight into the qualitative experiences of Asian American…

  13. Sexual selection affects the evolution of lifespan and ageing in the decorated cricket Gryllodes sigillatus.

    Science.gov (United States)

    Archer, C R; Zajitschek, F; Sakaluk, S K; Royle, N J; Hunt, J

    2012-10-01

    Recent work suggests that sexual selection can influence the evolution of ageing and lifespan by shaping the optimal timing and relative costliness of reproductive effort in the sexes. We used inbred lines of the decorated cricket, Gryllodes sigillatus, to estimate the genetic (co)variance between age-dependent reproductive effort, lifespan, and ageing within and between the sexes. Sexual selection theory predicts that males should die sooner and age more rapidly than females. However, a reversal of this pattern may be favored if reproductive effort increases with age in males but not in females. We found that male calling effort increased with age, whereas female fecundity decreased, and that males lived longer and aged more slowly than females. These divergent life-history strategies were underpinned by a positive genetic correlation between early-life reproductive effort and ageing rate in both sexes, although this relationship was stronger in females. Despite these sex differences in life-history schedules, age-dependent reproductive effort, lifespan, and ageing exhibited strong positive intersexual genetic correlations. This should, in theory, constrain the independent evolution of these traits in the sexes and may promote intralocus sexual conflict. Our study highlights the importance of sexual selection to the evolution of sex differences in ageing and lifespan in G. sigillatus. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  14. Beat Synchronization across the Lifespan: Intersection of Development and Musical Experience

    OpenAIRE

    Thompson, Elaine C.; White-Schwoch, Travis; Tierney, Adam; Kraus, Nina

    2015-01-01

    Rhythmic entrainment, or beat synchronization, provides an opportunity to understand how multiple systems operate together to integrate sensory-motor information. Also, synchronization is an essential component of musical performance that may be enhanced through musical training. Investigations of rhythmic entrainment have revealed a developmental trajectory across the lifespan, showing synchronization improves with age and musical experience. Here, we explore the development and maintenance ...

  15. Neoplastic and life-span effects of chronic exposure to tritium. II. Rats exposed in utero

    International Nuclear Information System (INIS)

    Cahill, D.F.; Wright, J.F.; Godbold, J.H.; Ward, J.M.; Laskey, J.W.; Tompkins, E.A.

    1975-01-01

    A study was conducted to determine the effects on neoplasia incidence and life-span of exposure in utero to a major environmental radionuclide. Sprague-Dawley rats were continuously exposed to tritiated water (HTO) from conception through birth in doses of 0, 1, 10, 50, and 100 μCi HTO/ml body water. HTO administration was terminated at birth. Calculated cumulative doses during gestation were approximately 0, 6.6, 66, 330, and 660 rads of total body irradiation. Under these exposure conditions, the two highest doses resulted in sterile offspring. Animals surviving through 30 days postnatally were defined as the study population and observed until their deaths. Intrauterine exposures to doses up to 66 rads had no significant effects on either sex with respect to lifespan, overall neoplasia incidence, incidence rate, or onset of mammary fibroadenomas. Females exposed to 330 or 660 rads were sterile and had lower incidence rates of mammary fibroadenomas than did controls; at 660 rads females had a lower incidence of overall neoplasia and reduced mean lifespans. Sterile male offspring had reduced mean longevity after irradiation at 660 rads. Regardless of dose group, females had significantly higher incidences of neoplasia and longer life-spans than males

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  17. Mental illness and mental health: The two continua model across the lifespan

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    Science.gov (United States)

    Billingsley, James; Carlson, Kimberly A.

    2010-01-01

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

  19. An Adaptation, Validity and Reliability of the Lifespan Sibling Relationship Scale to the Turkish Adolescents

    Science.gov (United States)

    Öz, F. Selda

    2015-01-01

    The purpose of this study is to adapt the Lifespan Sibling Relationship Scale (LSRS) developed by Riggio (2000) to Turkish. The scale with its original form in English consists of 48 items in total. The original scale was translated into Turkish by three instructors who are proficient both in the field and the language. Later, the original and…

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

    Science.gov (United States)

    Atanasov, Atanas Todorov

    2016-12-01

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

  1. On personality stability and change: main results of Brno longitudinal study on life-span development

    Czech Academy of Sciences Publication Activity Database

    Blatný, Marek

    2007-01-01

    Roč. 51, Supplement (2007), s. 37-49 ISSN 0009-062X R&D Projects: GA ČR(CZ) GA406/06/1408 Institutional research plan: CEZ:AV0Z70250504 Keywords : life-span development * personality stability and change Subject RIV: AN - Psychology Impact factor: 0.133, year: 2007

  2. CAMKII and calcineurin regulate the lifespan of Caenorhabditis elegans through the FOXO transcription factor DAF-16.

    Science.gov (United States)

    Tao, Li; Xie, Qi; Ding, Yue-He; Li, Shang-Tong; Peng, Shengyi; Zhang, Yan-Ping; Tan, Dan; Yuan, Zengqiang; Dong, Meng-Qiu

    2013-06-25

    The insulin-like signaling pathway maintains a relatively short wild-type lifespan in Caenorhabditis elegans by phosphorylating and inactivating DAF-16, the ortholog of the FOXO transcription factors of mammalian cells. DAF-16 is phosphorylated by the AKT kinases, preventing its nuclear translocation. Calcineurin (PP2B phosphatase) also limits the lifespan of C. elegans, but the mechanism through which it does so is unknown. Herein, we show that TAX-6•CNB-1 and UNC-43, the C. elegans Calcineurin and Ca(2+)/calmodulin-dependent kinase type II (CAMKII) orthologs, respectively, also regulate lifespan through DAF-16. Moreover, UNC-43 regulates DAF-16 in response to various stress conditions, including starvation, heat or oxidative stress, and cooperatively contributes to lifespan regulation by insulin signaling. However, unlike insulin signaling, UNC-43 phosphorylates and activates DAF-16, thus promoting its nuclear localization. The phosphorylation of DAF-16 at S286 by UNC-43 is removed by TAX-6•CNB-1, leading to DAF-16 inactivation. Mammalian FOXO3 is also regulated by CAMKIIA and Calcineurin. DOI:http://dx.doi.org/10.7554/eLife.00518.001.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  4. Vocabulary Skills in Adulthood: Longitudinal Relations with Cognitive and Personality Measures Across the Life-Span

    Czech Academy of Sciences Publication Activity Database

    Smolík, Filip; Blatný, Marek; Jelínek, Martin; Millová, Katarína; Sobotková, Veronika

    2016-01-01

    Roč. 60, č. 2 (2016), s. 97-105 ISSN 0009-062X R&D Projects: GA ČR GAP407/10/2410 Institutional support: RVO:68081740 Keywords : vocabulary * personality * life-span development * verbal IQ Subject RIV: AN - Psychology Impact factor: 0.242, year: 2016

  5. Basis for selecting optimum antibiotic regimens for secondary peritonitis.

    Science.gov (United States)

    Maseda, Emilio; Gimenez, Maria-Jose; Gilsanz, Fernando; Aguilar, Lorenzo

    2016-01-01

    Adequate management of severely ill patients with secondary peritonitis requires supportive therapy of organ dysfunction, source control of infection and antimicrobial therapy. Since secondary peritonitis is polymicrobial, appropriate empiric therapy requires combination therapy in order to achieve the needed coverage for both common and more unusual organisms. This article reviews etiological agents, resistance mechanisms and their prevalence, how and when to cover them and guidelines for treatment in the literature. Local surveillances are the basis for the selection of compounds in antibiotic regimens, which should be further adapted to the increasing number of patients with risk factors for resistance (clinical setting, comorbidities, previous antibiotic treatments, previous colonization, severity…). Inadequate antimicrobial regimens are strongly associated with unfavorable outcomes. Awareness of resistance epidemiology and of clinical consequences of inadequate therapy against resistant bacteria is crucial for clinicians treating secondary peritonitis, with delicate balance between optimization of empirical therapy (improving outcomes) and antimicrobial overuse (increasing resistance emergence).

  6. A comparative study of various therapeutic regimens in urticaria

    Directory of Open Access Journals (Sweden)

    Mukhopadhyay Amiyakumar

    1995-01-01

    Full Text Available 127 patients of urticaria were treated with chlorpheniramine maleate alone and in combination with cyproheptadine hydrochloride, ranitidine and doxepin and levamisole. Chlorpheniramine and doxepin combination showed a satisfactory result in 88.46% of patients. Overall study showed that a combination regimen is better than the antihistaminics alone. Drowsiness was the commonest side effect. Levamisole and chlorpheniramine maleate combination was found to be more effective than the antihimstamine alone.

  7. Comparison of Current Recommended Regimens of Atropinization in Organophosphate Poisoning

    OpenAIRE

    Connors, Nicholas J.; Harnett, Zachary H.; Hoffman, Robert S.

    2013-01-01

    Atropine is the mainstay of therapy in organophosphate (OP) toxicity, though research and consensus on dosing is lacking. In 2004, as reported by Eddleston et al. (J Toxicol Clin Toxicol 42(6):865-75, 2004), they noted variation in recommended regimens. We assessed revisions of original references, additional citations, and electronic sources to determine the current variability in atropine dosing recommendations. Updated editions of references from Eddleston et al.’s work, texts of Internal ...

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

    Directory of Open Access Journals (Sweden)

    Olivier Barré

    2017-02-01

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

  9. The Extended Enterprise concept

    DEFF Research Database (Denmark)

    Larsen, Lars Bjørn; Vesterager, Johan; Gobbi, Chiara

    1999-01-01

    This paper provides an overview of the work that has been done regarding the Extended Enterprise concept in the Common Concept team of Globeman 21 including references to results deliverables concerning the development of the Extended Enterprise concept. The first section presents the basic concept...... picture from Globeman21, which illustrates the Globeman21 way of realising the Extended Enterprise concept. The second section presents the Globeman21 EE concept in a life cycle perspective, which to a large extent is based on the thoughts and ideas behind GERAM (ISO/DIS 15704)....

  10. Preclinical Evaluations To Identify Optimal Linezolid Regimens for Tuberculosis Therapy

    Science.gov (United States)

    Drusano, George L.; Adams, Jonathan R.; Rodriquez, Jaime L.; Jambunathan, Kalyani; Baluya, Dodge L.; Brown, David L.; Kwara, Awewura; Mirsalis, Jon C.; Hafner, Richard; Louie, Arnold

    2015-01-01

    ABSTRACT Linezolid is an oxazolidinone with potent activity against Mycobacterium tuberculosis. Linezolid toxicity in patients correlates with the dose and duration of therapy. These toxicities are attributable to the inhibition of mitochondrial protein synthesis. Clinically relevant linezolid regimens were simulated in the in vitro hollow-fiber infection model (HFIM) system to identify the linezolid therapies that minimize toxicity, maximize antibacterial activity, and prevent drug resistance. Linezolid inhibited mitochondrial proteins in an exposure-dependent manner, with toxicity being driven by trough concentrations. Once-daily linezolid killed M. tuberculosis in an exposure-dependent manner. Further, 300 mg linezolid given every 12 hours generated more bacterial kill but more toxicity than 600 mg linezolid given once daily. None of the regimens prevented linezolid resistance. These findings show that with linezolid monotherapy, a clear tradeoff exists between antibacterial activity and toxicity. By identifying the pharmacokinetic parameters linked with toxicity and antibacterial activity, these data can provide guidance for clinical trials evaluating linezolid in multidrug antituberculosis regimens. PMID:26530386

  11. New drugs and perspectives for new anti-tuberculosis regimens

    Directory of Open Access Journals (Sweden)

    S. Tiberi

    2018-03-01

    Full Text Available Tuberculosis (TB is the ninth cause of global death, more than any other infectious disease. With growing drug resistance the epidemic remains and will require significant attention and investment for the elimination of this disease to occur. With susceptible TB treatment not changing over the last four decades and the advent of drug resistance, new drugs and regimens are required.Recently, through greater collaboration and research networks some progress with significant advances has taken place, not withstanding the comparatively low amount of resources invested. Of late the availability of the new drugs bedaquiline, delamanid and repurposed drugs linezolid, clofazimine and carbapenems are being used more frequently in drug-resistant TB regimens.The WHO shorter multidrug-resistant tuberculosis regimen promises to reach more patients and treat them more quickly and more cheaply.With this new enthusiasm and hope we this review gives an update on the new drugs and perspectives for the treatment of drug-susceptible and drug-resistant tuberculosis. Keywords: Bedaquiline, Delamanid, Linezolid, MDR, XDR-TB, TB

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

    Science.gov (United States)

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

    2015-01-01

    Bacteria serve as live food and nutrients for bacterial-feeding nematodes (BFNs) in soils, and influence nematodes behavior and physiology through their metabolism. Five bacterial taxa (Bacillus amyloliquefaciens JX1, Variovorax sp. JX14, Bacillus megaterium JX15, Pseudomonas fluorescens Y1 and Escherichia coli OP50) and the typical BFN Caenorhabditis elegans were selected to study the effects of bacterial respiration and growth rates on the feeding preferences, brood size and lifespan of nematodes. P. fluorescens Y1 and E. coli OP50 were found to be more active, with high respiration and rapid growth, whereas B. amyloliquefaciens JX1 and B. megaterium JX15 were inactive. The nematode C. elegans preferred active P. fluorescens Y1 and E. coli OP50 obviously. Furthermore, worms that fed on these two active bacteria produced more offspring but had shorter lifespan, while inactive and less preferred bacteria had increased nematodes lifespan and decreased the brood size. Based on these results, we propose that the bacterial activity may influence the behavior and life traits of C. elegans in the following ways: (1) active bacteria reproduce rapidly and emit high levels of CO2 attracting C. elegans; (2) these active bacteria use more resources in the nematodes’ gut to sustain their survival and reproduction, thereby reducing the worm's lifespan; (3) inactive bacteria may provide less food for worms than active bacteria, thus increasing nematodes lifespan but decreasing their fertility. Nematodes generally require a balance between their preferred foods and beneficial foods, only preferred food may not be beneficial for nematodes. PMID:26222828

  13. Lifespan and reproduction in brain-specific miR-29-knockdown mouse.

    Science.gov (United States)

    Takeda, Toru; Tanabe, Hiroyuki

    2016-03-18

    The microRNA miR-29 is widely distributed and highly expressed in adult mouse brain during the mouse's lifetime. We recently created conditional mutant mice whose miR-29 was brain-specifically knocked down through overexpression of an antisense RNA transgene against miR-29. To explore a role for brain miR-29 in maximizing organismal fitness, we assessed somatic growth, reproduction, and lifespan in the miR-29-knockdown (KD) mice and their wild-type (WT) littermates. The KD mice were developmentally indistinguishable from WT mice with respect to gross morphology and physical activity. Fertility testing revealed that KD males were subfertile, whereas KD females were hyperfertile, only in terms of reproductive success, when compared to their gender-matched WT correspondents. Another phenotypic difference between KD and WT animals appeared in their lifespan data; KD males displayed an overall increasing tendency in post-reproductive survival relative to WT males. In contrast, KD females were prone to shorter lifespans than WT females. These results clarify that brain-targeted miR-29 knockdown affects both lifespan and reproduction in a gender-dependent manner, and moreover that the reciprocal responsiveness to the miR-29 knockdown between these two phenotypes in both genders closely follow life-course models based on the classical trade-off prediction wherein elaborate early-life energetic investment in reproduction entails accelerated late-life declines in survival, and vice versa. Thus, this study identified miR-29 as the first mammalian miRNA that is directly implicated in the lifetime trade-off between the two major fitness components, lifespan and reproduction. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan.

    Science.gov (United States)

    Nomi, Jason S; Bolt, Taylor S; Ezie, C E Chiemeka; Uddin, Lucina Q; Heller, Aaron S

    2017-05-31

    Variability of neuronal responses is thought to underlie flexible and optimal brain function. Because previous work investigating BOLD signal variability has been conducted within task-based fMRI contexts on adults and older individuals, very little is currently known regarding regional changes in spontaneous BOLD signal variability in the human brain across the lifespan. The current study used resting-state fMRI data from a large sample of male and female human participants covering a wide age range (6-85 years) across two different fMRI acquisition parameters (TR = 0.645 and 1.4 s). Variability in brain regions including a key node of the salience network (anterior insula) increased linearly across the lifespan across datasets. In contrast, variability in most other large-scale networks decreased linearly over the lifespan. These results demonstrate unique lifespan trajectories of BOLD variability related to specific regions of the brain and add to a growing literature demonstrating the importance of identifying normative trajectories of functional brain maturation. SIGNIFICANCE STATEMENT Although brain signal variability has traditionally been considered a source of unwanted noise, recent work demonstrates that variability in brain signals during task performance is related to brain maturation in old age as well as individual differences in behavioral performance. The current results demonstrate that intrinsic fluctuations in resting-state variability exhibit unique maturation trajectories in specific brain regions and systems, particularly those supporting salience detection. These results have implications for investigations of brain development and aging, as well as interpretations of brain function underlying behavioral changes across the lifespan. Copyright © 2017 the authors 0270-6474/17/375539-10$15.00/0.

  15. Tomatidine enhances lifespan and healthspan in C. elegans through mitophagy induction via the SKN-1/Nrf2 pathway.

    Science.gov (United States)

    Fang, Evandro F; Waltz, Tyler B; Kassahun, Henok; Lu, Qiping; Kerr, Jesse S; Morevati, Marya; Fivenson, Elayne M; Wollman, Bradley N; Marosi, Krisztina; Wilson, Mark A; Iser, Wendy B; Eckley, D Mark; Zhang, Yongqing; Lehrmann, Elin; Goldberg, Ilya G; Scheibye-Knudsen, Morten; Mattson, Mark P; Nilsen, Hilde; Bohr, Vilhelm A; Becker, Kevin G

    2017-04-11

    Aging is a major international concern that brings formidable socioeconomic and healthcare challenges. Small molecules capable of improving the health of older individuals are being explored. Small molecules that enhance cellular stress resistance are a promising avenue to alleviate declines seen in human aging. Tomatidine, a natural compound abundant in unripe tomatoes, inhibits age-related skeletal muscle atrophy in mice. Here we show that tomatidine extends lifespan and healthspan in C. elegans, an animal model of aging which shares many major longevity pathways with mammals. Tomatidine improves many C. elegans behaviors related to healthspan and muscle health, including increased pharyngeal pumping, swimming movement, and reduced percentage of severely damaged muscle cells. Microarray, imaging, and behavioral analyses reveal that tomatidine maintains mitochondrial homeostasis by modulating mitochondrial biogenesis and PINK-1/DCT-1-dependent mitophagy. Mechanistically, tomatidine induces mitochondrial hormesis by mildly inducing ROS production, which in turn activates the SKN-1/Nrf2 pathway and possibly other cellular antioxidant response pathways, followed by increased mitophagy. This mechanism occurs in C. elegans, primary rat neurons, and human cells. Our data suggest that tomatidine may delay some physiological aspects of aging, and points to new approaches for pharmacological interventions for diseases of aging.

  16. An extended technicolor model

    International Nuclear Information System (INIS)

    Appelquist, T.; Terning, J.

    1994-01-01

    An extended technicolor model is constructed. Quark and lepton masses, spontaneous CP violation, and precision electroweak measurements are discussed. Dynamical symmetry breaking is analyzed using the concept of the big MAC (most attractive channel)

  17. Extending mine life

    International Nuclear Information System (INIS)

    Anon.

    1984-01-01

    Mine layouts, new machines and techniques, research into problem areas of ground control and so on, are highlighted in this report on extending mine life. The main resources taken into account are coal mining, uranium mining, molybdenum and gold mining

  18. Rational extended thermodynamics

    CERN Document Server

    Müller, Ingo

    1998-01-01

    Ordinary thermodynamics provides reliable results when the thermodynamic fields are smooth, in the sense that there are no steep gradients and no rapid changes. In fluids and gases this is the domain of the equations of Navier-Stokes and Fourier. Extended thermodynamics becomes relevant for rapidly varying and strongly inhomogeneous processes. Thus the propagation of high­ frequency waves, and the shape of shock waves, and the regression of small-scale fluctuation are governed by extended thermodynamics. The field equations of ordinary thermodynamics are parabolic while extended thermodynamics is governed by hyperbolic systems. The main ingredients of extended thermodynamics are • field equations of balance type, • constitutive quantities depending on the present local state and • entropy as a concave function of the state variables. This set of assumptions leads to first order quasi-linear symmetric hyperbolic systems of field equations; it guarantees the well-posedness of initial value problems and f...

  19. The dialogically extended mind

    DEFF Research Database (Denmark)

    Fusaroli, Riccardo; Gangopadhyay, Nivedita; Tylén, Kristian

    2014-01-01

    A growing conceptual and empirical literature is advancing the idea that language extends our cognitive skills. One of the most influential positions holds that language – qua material symbols – facilitates individual thought processes by virtue of its material properties. Extending upon this model...... relate our approach to other ideas about collective minds and review a number of empirical studies to identify the mechanisms enabling the constitution of interpersonal cognitive systems....

  20. Extending Mondrian Memory Protection

    Science.gov (United States)

    2010-11-01

    a kernel semaphore is locked or unlocked. In addition, we extended the system call interface to receive notifications about user-land locking...operations (such as calls to the mutex and semaphore code provided by the C library). By patching the dynamically loadable GLibC5, we are able to test... semaphores , and spinlocks. RTO-MP-IST-091 10- 9 Extending Mondrian Memory Protection to loading extension plugins. This prevents any untrusted code

  1. Extended Life Coolant Testing

    Science.gov (United States)

    2016-06-06

    number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 06-06-2016 2. REPORT TYPE Interim Report 3. DATES COVERED ... Corrosion Testing of Traditional and Extended Life Coolants 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Hansen, Gregory A. T...providing vehicle specific coolants. Several laboratory corrosion tests were performed according to ASTM D1384 and D2570, but with a 2.5x extended time

  2. The lifespan of semiconductor patents by assignee and patent characteristics

    Directory of Open Access Journals (Sweden)

    Chang Shu-Hao

    2017-01-01

    Full Text Available Evaluating the values of patents is critical for both managers and investors. Patent maintenance time is an ideal proxy indicator for evaluating commercial patent value. This study investigated the survival rates of patents in the semiconductor industry by using a survival analysis and incorporated a predictive model for patent maintenance times. The technical characteristics of the patents, the assignee factors, and the statuses of the patents were used as the predictive factors for patent maintenance time. The results revealed a small entity size and the number of assignees are the risk factors that increase the likelihood of the maintenance time of a patent decreasing. The litigation status of a patent and the number of its international patent classifications, claims, forward citations, and assignments were determined to be the protection factors that raise the likelihood of its maintenance time extending. Additionally, substantial differences were noted between small entities and nonsmall entities and between being litigated and not in their effects on the survival rates of patents. This study examined the factors that affect the survival rates of patents and provides a reference for the managers and investors of intellectual property rights to use when assessing technical and commercial patent values.

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

    Science.gov (United States)

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

    2014-12-01

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

  4. Phylogenetic relationship and Fourier-transform infrared spectroscopy-derived lipid determinants of lifespan parameters in the Saccharomyces cerevisiae yeast.

    Science.gov (United States)

    Molon, Mateusz; Zebrowski, Jacek

    2017-06-01

    Yeast ageing has been gaining much attention in gerontology research, yet the process itself is still not entirely clear. One of the constraints related to the use of the Saccharomyces cerevisiae yeast in studies is the ambiguity of the results concerning ageing determinants for different genetic backgrounds. In this paper, we compare reproductive potentials and lifespans of seven widely used haploid laboratory strains differing in daughter cells production capabilities and highlight the importance of choosing an appropriate genotype for the studies on ageing. Moreover, we show here links between post-reproductive lifespan and lipid metabolism, as well as between reproductive potential, reproductive lifespan and phylogenetic relationship. Using FTIR spectroscopy that generated a biochemical fingerprint of cells, coupled with chemometrics, we found that the band of carbonyl (C = O) stretching vibration discriminates the strains according to post-reproductive lifespan. The results indicated that prolonged post-reproductive lifespan was associated with relatively lower amount of fatty acids esterified to phospholipids compared to a free acid pool, thus implying phospholipid metabolism for the post-reproductive lifespan of yeast. In addition, phylogenetic analysis showed a correlation between nucleotide similarity and the reproductive potential or reproductive lifespan, but not to the longevity expressed in time units. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

    DEFF Research Database (Denmark)

    Sacco, Ralph L; Diener, Hans-Christoph; Yusuf, Salim

    2008-01-01

    BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly...

  6. Extended spider cognition.

    Science.gov (United States)

    Japyassú, Hilton F; Laland, Kevin N

    2017-05-01

    There is a tension between the conception of cognition as a central nervous system (CNS) process and a view of cognition as extending towards the body or the contiguous environment. The centralised conception requires large or complex nervous systems to cope with complex environments. Conversely, the extended conception involves the outsourcing of information processing to the body or environment, thus making fewer demands on the processing power of the CNS. The evolution of extended cognition should be particularly favoured among small, generalist predators such as spiders, and here, we review the literature to evaluate the fit of empirical data with these contrasting models of cognition. Spiders do not seem to be cognitively limited, displaying a large diversity of learning processes, from habituation to contextual learning, including a sense of numerosity. To tease apart the central from the extended cognition, we apply the mutual manipulability criterion, testing the existence of reciprocal causal links between the putative elements of the system. We conclude that the web threads and configurations are integral parts of the cognitive systems. The extension of cognition to the web helps to explain some puzzling features of spider behaviour and seems to promote evolvability within the group, enhancing innovation through cognitive connectivity to variable habitat features. Graded changes in relative brain size could also be explained by outsourcing information processing to environmental features. More generally, niche-constructed structures emerge as prime candidates for extending animal cognition, generating the selective pressures that help to shape the evolving cognitive system.

  7. Extending quantum mechanics entails extending special relativity

    International Nuclear Information System (INIS)

    Aravinda, S; Srikanth, R

    2016-01-01

    The complementarity between signaling and randomness in any communicated resource that can simulate singlet statistics is generalized by relaxing the assumption of free will in the choice of measurement settings. We show how to construct an ontological extension for quantum mechanics (QMs) through the oblivious embedding of a sound simulation protocol in a Newtonian spacetime. Minkowski or other intermediate spacetimes are ruled out as the locus of the embedding by virtue of hidden influence inequalities. The complementarity transferred from a simulation to the extension unifies a number of results about quantum non-locality, and implies that special relativity has a different significance for the ontological model and for the operational theory it reproduces. Only the latter, being experimentally accessible, is required to be Lorentz covariant. There may be certain Lorentz non-covariant elements at the ontological level, but they will be inaccessible at the operational level in a valid extension. Certain arguments against the extendability of QM, due to Conway and Kochen (2009) and Colbeck and Renner (2012), are attributed to their assumption that the spacetime at the ontological level has Minkowski causal structure. (paper)

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

    Science.gov (United States)

    Li, Yan-Hui; Zhang, Gai-Gai

    2016-04-12

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

  9. Esquemas alternativos de hemodiálise Alternative hemodialysis regimens

    Directory of Open Access Journals (Sweden)

    Jorge Paulo Strogoff de Matos

    2010-03-01

    Full Text Available A taxa de mortalidade entre os pacientes em hemodiálise (HD é extremamente elevada. A expectativa de vida restante de um paciente ao iniciar HD é apenas cerca de um quarto daquela da população geral com a mesma idade. O esquema convencional de HD, com três sessões semanais de cerca de quatro horas, foi estabelecido de maneira empírica há cerca de quatro décadas e merece ser reavaliado criticamente. Desde a falha do Estudo HEMO em demonstrar benefícios clínicos com o aumento do Kt/V de ureia nos pacientes em esquema convencional de HD, tem havido um crescente interesse pelos esquemas alternativos de HD com o intuito de prover um tratamento associado com uma melhor sobrevida. Dentre os esquemas mais promissores, destacam-se a HD diária de curta duração e a HD noturna prolongada. As limitações econômicas que inibem a aplicação dos conhecimentos emergentes nesta área devem ser vencidas.The mortality rate among patients on hemodialysis (HD is extremely high. Remaining life expectancy for a patient initiating HD is only approximately one quarter of that of the general population at the same age bracket. The conventional HD regimen based on four-hour sessions three times a week was empirically established nearly four decades ago and needs to be revisited. Since the failure of the HEMO Study to demonstrate the clinical benefits of higher urea Kt/V for patients on conventional HD, an increasing interest for alternative HD regimens has emerged aiming at providing a treatment for improving survival rates. Short daily HD and long nocturnal HD stand out as the most promising alternative regimens. Economical obstacles which could hinder the clinical application of emerging knowledge in the field should be overcome.

  10. Predictors of nonadherence with blood pressure regimens in hemodialysis

    Directory of Open Access Journals (Sweden)

    Kauric-Klein Z

    2013-09-01

    Full Text Available Zorica Kauric-KleinCollege of Nursing, Wayne State University, Detroit, MI, USABackground: Hypertension is very poorly controlled in patients on hemodialysis (HD. Demographic and psychosocial predictors of nonadherence with blood pressure (BP regimens in HD have not been investigated. A study of 118 HD patients from six outpatient HD units was conducted to determine the relationship between demographic/psychosocial factors and adherence with BP-related regimens, ie, fluid restriction, BP medication adherence, and HD treatment adherence.Methods: Descriptive statistics, Pearson correlations, and multiple regressions were conducted to analyze and determine the relationships between variables.Results: Younger age was related to increased fluid gains (r = -0.37, P < 0.01, decreased medication adherence (r = -0.19, P = 0.04, increased missed HD treatments (r = -0.37, P < 0.01, and diastolic BP (r = -0.60, P < 0.01. Female sex was significantly related to decreased fluid gains (r = -0.28, P < 0.01. Race was related to increased missed HD treatments (r = 0.22, P = 0.02. Increased social support was related to decreased missed HD treatments (r = -0.22, P = 0.02. Depression scores were inversely related to decreased medication adherence scores (r = 0.24, P = 0.01.Conclusion: By identifying risk factors for nonadherence with BP-related regimens (young age, male sex, decreased social support, and depression, health care providers can plan early clinical intervention to minimize the risk of nonadherence.Keywords: nonadherence, hemodialysis, blood pressure, demographic predictors, psychosocial predictors

  11. Comparison of current recommended regimens of atropinization in organophosphate poisoning.

    Science.gov (United States)

    Connors, Nicholas J; Harnett, Zachary H; Hoffman, Robert S

    2014-06-01

    Atropine is the mainstay of therapy in organophosphate (OP) toxicity, though research and consensus on dosing is lacking. In 2004, as reported by Eddleston et al. (J Toxicol Clin Toxicol 42(6):865-75, 2004), they noted variation in recommended regimens. We assessed revisions of original references, additional citations, and electronic sources to determine the current variability in atropine dosing recommendations. Updated editions of references from Eddleston et al.'s work, texts of Internal and Emergency Medicine, and electronic resources were reviewed for atropine dosing recommendations. For comparison, recommendations were assessed using the same mean dose (23.4 mg) and the highest dose (75 mg) of atropine as used in the original paper. Recommendations were also compared with the dosing regimen from the World Health Organization (WHO). Thirteen of the original recommendations were updated and 15 additional references were added giving a convenience sample of 28. Sufficient information to calculate time to targeted dose was provided by 24 of these samples. Compared to 2004, current recommendations have greatly increased the speed of atropinization with 13/24 able to reach the mean and high atropine dose within 30 min compared to 1/36 in 2004. In 2004, there were 13 regimens where the maximum time to reach 75 mg was over 18 h, whereas now, there are 2. While only one recommendation called for doubling the dose for faster escalation in 2004, 15 of the 24 current works include dose doubling. In 2004, Eddleston et al. called for an evidence-based guideline for the treatment of OP poisoning that could be disseminated worldwide. Many current recommendations can adequately treat patients within 1 h. While the WHO recommendations remain slow to treat patients with OP poisoning, other authorities are close to a consensus on rapid atropinization.

  12. Toward an Integrative Science of Life-Span Development and Aging

    Science.gov (United States)

    Piccinin, Andrea M.

    2010-01-01

    The study of aging demands an integrative life-span developmental framework, involving interdisciplinary collaborations and multiple methodological approaches for understanding how and why individuals change, in both normative and idiosyncratic ways. We highlight and summarize some of the issues encountered when conducting integrative research for understanding aging-related change, including, the integration of results across different levels of analysis; the integration of theory, design, and analysis; and the synthesis of results across studies of aging. We emphasize the necessity of longitudinal designs for understanding development and aging and discuss methodological issues that should be considered for achieving reproducible research on within-person processes. It will be important that current and future studies permit opportunities for quantitative comparison across populations given the extent to which historical shifts and cultural differences influence life-span processes and aging-related outcomes. PMID:20237144

  13. Weight concern across the life-span: relationship to self-esteem and feminist identity.

    Science.gov (United States)

    Tiggemann, M; Stevens, C

    1999-07-01

    The aim of this study was to investigate the correlates of weight concern across the life-span. Questionnaires assessing weight concern, self-esteem, and feminist attitudes were completed in their homes by 180 women aged between 18 and 60 years. It was found that there was a negative relationship between weight concern and self-esteem for 30 to 49-year-old women, but not for younger or older women. A similar pattern held for feminist attitudes. Among 30 to 49-year-old women, a strong feminist orientation related to a lesser concern with weight. It was concluded that the meaning and experience of body weight and size change across the life-span.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  15. An Extended Duopoly Game.

    Science.gov (United States)

    Eckalbar, John C.

    2002-01-01

    Illustrates how principles and intermediate microeconomic students can gain an understanding for strategic price setting by playing a relatively large oligopoly game. Explains that the game extends to a continuous price space and outlines appropriate applications. Offers the Mathematica code to instructors so that the assumptions of the game can…

  16. Transversally extended string

    International Nuclear Information System (INIS)

    Akama, Keiichi

    1988-01-01

    Starting with the space-time action of the transversally extended string, we derive its world-sheet action, which is that of a gravitational and gauge theory with matter fields on the world-sheet, with additional effects of the second fundamental quantity. (author)

  17. Extended artistic appreciation.

    Science.gov (United States)

    Wilson, Robert A

    2013-04-01

    I propose that in at least some cases, objects of artistic appreciation are best thought of not simply as causes of artistic appreciation, but as parts of the cognitive machinery that drives aesthetic appreciation. In effect, this is to say that aesthetic appreciation operates via extended cognitive systems.

  18. Towards Extended Vantage Theory

    Science.gov (United States)

    Glaz, Adam

    2010-01-01

    The applicability of Vantage Theory (VT), a model of (colour) categorization, to linguistic data largely depends on the modifications and adaptations of the model for the purpose. An attempt to do so proposed here, called Extended Vantage Theory (EVT), slightly reformulates the VT conception of vantage by capitalizing on some of the entailments of…

  19. An Acute Lateral Ankle Sprain Significantly Decreases Physical Activity across the Lifespan

    Directory of Open Access Journals (Sweden)

    Tricia Hubbard-Turner, Erik A. Wikstrom, Sophie Guderian, Michael J. Turner

    2015-09-01

    Full Text Available We do not know the impact an ankle sprain has on physical activity levels across the lifespan. With the negative consequences of physical inactivity well established, understanding the effect of an ankle sprain on this outcome is critical. The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model. Thirty male mice (CBA/J were randomly placed into one of three groups: the transected calcaneofibular ligament (CFL group, the transected anterior talofibular ligament (ATFL/CFL group, and a SHAM group. Three days after surgery, all of the mice were individually housed in a cage containing a solid surface running wheel. Physical activity levels were recorded and averaged every week across the mouse’s lifespan. The SHAM mice ran significantly more distance each day compared to the remaining two running groups (post hoc p = 0.011. Daily duration was different between the three running groups (p = 0.048. The SHAM mice ran significantly more minutes each day compared to the remaining two running groups (post hoc p=0.046 while the ATFL/CFL mice ran significantly less minutes each day (post hoc p = 0.028 compared to both the SHAM and CFL only group. The SHAM mice ran at a faster daily speed versus the remaining two groups of mice (post hoc p = 0.019 and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group (post hoc p = 0.005. The results of this study indicate that a single ankle sprain significantly decreases physical activity across the lifespan in mice. This decrease in physical activity can potentially lead to the development of numerous chronic diseases. An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately.

  20. Connectivity trajectory across lifespan differentiates the precuneus from the default network.

    Science.gov (United States)

    Yang, Zhi; Chang, Catie; Xu, Ting; Jiang, Lili; Handwerker, Daniel A; Castellanos, F Xavier; Milham, Michael P; Bandettini, Peter A; Zuo, Xi-Nian

    2014-04-01

    The default network of the human brain has drawn much attention due to its relevance to various brain disorders, cognition, and behavior. However, its functional components and boundaries have not been precisely defined. There is no consensus as to whether the precuneus, a hub in the functional connectome, acts as part of the default network. This discrepancy is more critical for brain development and aging studies: it is not clear whether age has a stronger impact on the default network or precuneus, or both. We used Generalized Ranking and Averaging Independent Component Analysis by Reproducibility (gRAICAR) to investigate the lifespan trajectories of intrinsic functional networks. By estimating individual-specific spatial components and aligning them across subjects, gRAICAR measures the spatial variation of component maps across a population without constraining the same components to appear in every subject. In a cross-lifespan fMRI dataset (N=126, 7-85years old), we observed stronger age dependence in the spatial pattern of a precuneus-dorsal posterior cingulate cortex network compared to the default network, despite the fact that the two networks exhibit considerable spatial overlap and temporal correlation. These results remained even when analyses were restricted to a subpopulation with very similar head motion across age. Our analyses further showed that the two networks tend to merge with increasing age. Post-hoc analyses of functional connectivity confirmed the distinguishable cross-lifespan trajectories between the two networks. Based on these observations, we proposed a dynamic model of cross-lifespan functional segregation and integration between the two networks, suggesting that the precuneus network may have a different functional role than the default network, which declines with age. These findings have implications for understanding the functional roles of the default network, gaining insight into its dynamics throughout life, and guiding

  1. The importance of adult life-span perspective in explaining variations in political ideology.

    Science.gov (United States)

    Sedek, Grzegorz; Kossowska, Malgorzata; Rydzewska, Klara

    2014-06-01

    As a comment on Hibbing et al.'s paper, we discuss the evolution of political and social views from more liberal to more conservative over the span of adulthood. We show that Hibbing et al.'s theoretical model creates a false prediction from this developmental perspective, as increased conservatism in the adult life-span trajectory is accompanied by the avoidance of negative bias.

  2. Magpies and mirrors : identity as a mediator of music preferences across the lifespan

    OpenAIRE

    Leadbeater, Richard; Marsden, Alan

    2014-01-01

    This thesis examines the role of identity on the development and trajectory of music preferences across the lifespan. The focus of interest in recent empirical research has been to predict music preferences using adolescent individual differences. It is widely recognized that adolescents use music to help them deal with a number of psychosocial and emotional challenges, which often arise during this critical period of identity development. There has been little study whether adults similarly ...

  3. Immigration, Language Proficiency, and Autobiographical Memories: Lifespan Distribution and Second-Language Access

    OpenAIRE

    Esposito, Alena G.; Baker-Ward, Lynne

    2015-01-01

    This investigation examined two controversies in the autobiographical literature: how cross-language immigration affects the distribution of autobiographical memories across the lifespan and under what circumstances language-dependent recall is observed. Both Spanish/English bilingual immigrants and English monolingual non-immigrants participated in a cue word study, with the bilingual sample taking part in a within-subject language manipulation. The expected bump in the num...

  4. Mitochondrial Respiratory Thresholds Regulate Yeast Chronological Lifespan and its Extension by Caloric Restriction

    OpenAIRE

    Ocampo, Alejandro; Liu, Jingjing; Schroeder, Elizabeth A.; Shadel, Gerald S.; Barrientos, Antoni

    2012-01-01

    We have explored the role of mitochondrial function in aging by genetically and pharmacologically modifying yeast cellular respiration production during the exponential and/or stationary growth phases, and determining how this affects chronological lifespan (CLS). Our results demonstrate that respiration is essential during both growth phases for standard CLS, but that yeast have a large respiratory capacity and only deficiencies below a threshold (~40% of wild-type) significantly curtail CLS...

  5. Effects of an unusual poison identify a lifespan role for Topoisomerase 2 in Saccharomyces cerevisiae

    OpenAIRE

    Tombline, Gregory; Millen, Jonathan I.; Polevoda, Bogdan; Rapaport, Matan; Baxter, Bonnie; Van Meter, Michael; Gilbertson, Matthew; Madrey, Joe; Piazza, Gary A.; Rasmussen, Lynn; Wennerberg, Krister; White, E. Lucile; Nitiss, John L.; Goldfarb, David S.

    2017-01-01

    A progressive loss of genome maintenance has been implicated as both a cause and consequence of aging. Here we present evidence supporting the hypothesis that an age-associated decay in genome maintenance promotes aging in Saccharomyces cerevisiae (yeast) due to an inability to sense or repair DNA damage by topoisomerase 2 (yTop2). We describe the characterization of LS1, identified in a high throughput screen for small molecules that shorten the replicative lifespan of yeast. LS1 accelerates...

  6. Effects of low doses of A-bomb radiation on human lifespan

    International Nuclear Information System (INIS)

    Okumura, Y.; Mine, M.

    1997-01-01

    Among about 100,000 A-bomb survivors registered at Nagasaki University School of Medicine, male subjects exposed to 31 - 40 cGy showed significantly lower mortality from non-cancerous diseases than age-matched unexposed males. And the death rate for exposed male and female was smaller than that for unexposed. It was presented that the low doses of A-bomb radiation increased lifespan of A-bomb survivors. (author)

  7. Sustained attention across the lifespan in a sample of 10,000: Dissociating ability and strategy

    OpenAIRE

    Fortenbaugh, Francesca C.; DeGutis, Joseph; Germine, Laura; Wilmer, Jeremy; Grosso, Mallory; Russo, Kathryn; Esterman, Michael

    2015-01-01

    Normal and abnormal differences in sustained visual attention have long been of interest to scientists, educators, and clinicians. Still lacking, however, is a clear understanding of how sustained visual attention varies across the broad sweep of the human lifespan. Here, we fill this gap in two ways. First, powered by an unprecedentedly large, 10,430-person sample, we model age-related differences with substantially greater precision than prior efforts. Second, using the recently developed g...

  8. Late effects of various dose-fractionation regimens

    International Nuclear Information System (INIS)

    Turesson, I.; Notter, G.

    1983-01-01

    These clinical investigations of various dose-fractionation regimens on human skin show that: The late reactions cannot be predicted from the early reactions; The dose-response curves for late reactions are much steeper than for early reactions; Equivalent doses for various fractionation schedules concerning late effects can be calculated by means of a corrected CRE (NSD) formula; the correction must be considered preliminary because further follow-up is needed. A clinical fractionation study of this type requires: Extremely careful dosimetry; Study of the same anatomical region; Very long follow-up; Studies at different effect levels; Skin reaction is the only end point we have studied systematically for different fractionation regimens. Experience with the CRE formula as a model for calculating isoeffect doses for different fractionation schedules in routine clinical use can be summarized as follows: The CRE formula has been used prospectively since 1972 in all patients; CRE-equivalent weekly doses to 5 x 2.0 Gy per week has been used. (Although the fractionation schedule is changed, the overall treatment time is still the same); The CRE range was 18 to 21 for curative radiotherapy on carcinomas; No irradiation was applied during pronounced acute reactions. No unexpected complications have been observed under these conditions

  9. Accelerated split course regimen in the treatment of brain metastases

    International Nuclear Information System (INIS)

    Franchin, G.; Minatel, E.; Roncadin, M.; Trovo, M.G.; De Paoli, A.; Bortolus, R.; Arcicasa, M.; Boz, G.; Gobitti, C.; Grigoletto, E.; Bassignano, G.

    1988-01-01

    63 patients, with brain metastases were treated with an accelerated split course regimen; irradiation was given to the whole brain in 3 daily fractions of 160 cGy each for 5 days a week. The cycle was repeated after 2 weeks to a total dose of 4800 cGy. Male-female ratio was 3:1. Median age was 58 years. The most frequent site of primary tumor was lung (41 patients), breast in 6 patients, melanoma in 3 patients, other sites in 8 patients and unknown cancer in 5 patients. Thirty-five patients had multiple brain metastases localizations. Two patients failed to complete the scheduled treatment: one because of early death and the other by refusal of therapy during treatment. Complete remission was obtained in 4 patients and partial remission in 24 patients. The median survival time was 21 weeks. The overall response rate was 42.5%. Toxicity was not considerable. The treatment results were not influenced by the site of primary tumor or by disease spreading; only the neurologic status before radiotherapy and the response to treatment influenced survival. The results obtained are similar to those reported by others; however, with the accelerated split course regimen the treatment time was reduced and a shorter period of hospitalization was required. 36 refs.; 2 figs.; 3 tabs

  10. Atypical Amniotic Fluid Embolism Managed with a Novel Therapeutic Regimen

    Directory of Open Access Journals (Sweden)

    Shadi Rezai

    2017-01-01

    Full Text Available Amniotic fluid embolism (AFE is the second leading cause of maternal mortality in the USA with an incidence of 1 : 15,200 births. The case fatality rate and perinatal mortality associated with AFE are 13–30% and 9–44%, respectively. This rare but devastating complication can be difficult to diagnose as many of the early signs and symptoms are nonspecific. Compounding this diagnostic challenge is a lack of effective treatment regimens which to date are mostly supportive. We present the case of a 26-year-old woman who suffered from suspected AFE and was successfully treated with the novel regimen of Atropine, Ondansetron, and Ketorolac (A-OK. The authors acknowledge that this case does not meet the new criteria proposed, by Clark in 2016, but feel that it is important to share this case report, due to dramatic patient response to the provided supportive therapy presented in this case report. We hope this case report will prompt further research into this novel approach to treating AFE with Atropine, Ondansetron, and Ketorolac.

  11. Predictive tools for designing new insulins and treatment regimens

    DEFF Research Database (Denmark)

    Klim, Søren

    The thesis deals with the development of "Predictive tools for designing new insulins and treatments regimens" and consists of two parts: A model based approach for bridging properties of new insulin analogues from glucose clamp experiments to meal tolerance tests (MTT) and a second part that des......The thesis deals with the development of "Predictive tools for designing new insulins and treatments regimens" and consists of two parts: A model based approach for bridging properties of new insulin analogues from glucose clamp experiments to meal tolerance tests (MTT) and a second part...... that describes an implemented software program able to handle stochastic differential equations (SDEs) with mixed effects. The thesis is supplemented with scientific papers published during the PhD. Developing an insulin analogue from candidate molecule to a clinical drug consists of a development programme...... and efficacy are investigated. Numerous methods are used to quantify dose and efficacy in Phase II - especially of interest is the 24-hour meal tolerance test as it tries to portray near normal living conditions. Part I describes an integrated model for insulin and glucose which is aimed at simulating 24-hour...

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

    Directory of Open Access Journals (Sweden)

    Marina eKovina

    2013-08-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

    Silva, Carlos; Annamalai, Kalyan

    2008-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Kalyan Annamalai

    2008-06-01

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

  16. Lifespan estimation of seal welded super stainless steels for water condenser of nuclear power plants

    Science.gov (United States)

    Kim, Young Sik; Park, Sujin; Chang, Hyun Young

    2014-01-01

    When sea water was used as cooling water for water condenser of nuclear power plants, commercial stainless steels can not be applied because chloride concentration exceeds 20,000 ppm. There are many opinions for the materials selection of tube and tube sheets of a condenser. This work reviewed the application guide line of stainless steels for sea-water facilities and the estimation equations of lifespan were proposed from the analyses of both field data for sea water condenser and experimental results of corrosion. Empirical equations for lifespan estimation were derived from the pit initiation time and re-tubing time of stainless steel tubing in sea water condenser of nuclear power plants. The lifespan of seal-welded super austenitic stainless steel tube/tube sheet was calculated from these equations. Critical pitting temperature of seal-welded PRE 50 grade super stainless steel was evaluated as 60 °C. Using the proposed equation in engineering aspect, tube pitting corrosion time of seal-welded tube/tube sheet was calculated as 69.8 years and re-tubing time was estimated as 82.0 years.

  17. Uncoupling protein homologs may provide a link between mitochondria, metabolism and lifespan.

    Science.gov (United States)

    Wolkow, Catherine A; Iser, Wendy B

    2006-05-01

    Uncoupling proteins (UCPs), which dissipate the mitochondrial proton gradient, have the ability to decouple mitochodrial respiration from ATP production. Since mitochondrial electron transport is a major source of free radical production, it is possible that UCP activity might impact free radical production. Free radicals can react with and damage cellular proteins, DNA and lipids. Accumulated damage from oxidative stress is believed to be a major contributor to cellular decline during aging. If UCP function were to impact mitochondrial free radical production, then one would expect to find a link between UCP activity and aging. This theory has recently been tested in a handful of organisms whose genomes contain UCP1 homologs. Interestingly, these experiments indicate that UCP homologs can affect lifespan, although they do not support a simple relationship between UCP activity and aging. Instead, UCP-like proteins appear to have a variety of effects on lifespan, and on pathways implicated in lifespan regulation. One possible explanation for this complex picture is that UCP homologs may have tissue-specific effects that complicate their effects on aging. Furthermore, the functional analysis of UCP1 homologs is incomplete. Thus, these proteins may perform functions in addition to, or instead of, mitochondrial uncoupling. Although these studies have not revealed a clear picture of UCP effects on aging, they have contributed to the growing knowledge base for these interesting proteins. Future biochemical and genetic investigation of UCP-like proteins will do much to clarify their functions and to identify the regulatory networks in which they are involved.

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

    Directory of Open Access Journals (Sweden)

    Portal-Celhay Cynthia

    2012-03-01

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

  19. Topological organization of the human brain functional connectome across the lifespan

    Directory of Open Access Journals (Sweden)

    Miao Cao

    2014-01-01

    Full Text Available Human brain function undergoes complex transformations across the lifespan. We employed resting-state functional MRI and graph-theory approaches to systematically chart the lifespan trajectory of the topological organization of human whole-brain functional networks in 126 healthy individuals ranging in age from 7 to 85 years. Brain networks were constructed by computing Pearson's correlations in blood-oxygenation-level-dependent temporal fluctuations among 1024 parcellation units followed by graph-based network analyses. We observed that the human brain functional connectome exhibited highly preserved non-random modular and rich club organization over the entire age range studied. Further quantitative analyses revealed linear decreases in modularity and inverted-U shaped trajectories of local efficiency and rich club architecture. Regionally heterogeneous age effects were mainly located in several hubs (e.g., default network, dorsal attention regions. Finally, we observed inverse trajectories of long- and short-distance functional connections, indicating that the reorganization of connectivity concentrates and distributes the brain's functional networks. Our results demonstrate topological changes in the whole-brain functional connectome across nearly the entire human lifespan, providing insights into the neural substrates underlying individual variations in behavior and cognition. These results have important implications for disease connectomics because they provide a baseline for evaluating network impairments in age-related neuropsychiatric disorders.

  20. How a Mutation that Slows Aging Can Also Disproportionately Extend End-of-Life Decrepitude

    Directory of Open Access Journals (Sweden)

    Katie Podshivalova

    2017-04-01

    Full Text Available Summary: The goal of aging research is to extend healthy, active life. For decades, C. elegans daf-2 insulin/insulin-like growth factor 1 (IGF-1 receptor mutants have served as a model for extended lifespan and youthfulness. However, a recent report suggested that their longevity is associated with an undesirable phenotype: a disproportionately long period of decrepitude at the end of life. In the human population, such an outcome would be a burden to society, bringing into question the relevance of daf-2 mutants as a model for life extension. However, here we report that, following an extended period of movement, daf-2 mutants survive longer in a decrepit state because of a beneficial trait: they are resistant to colonization of the digestive tract by dietary bacteria, a condition that leads to premature death in the wild-type and prevents their manifestation of decrepitude. If bacterial colonization is prevented, then daf-2 mutants lead both chronologically and proportionately healthier lives relative to the wild-type. : Podshivalova et al. show that long-lived C. elegans insulin/IGF-1 receptor mutants remain active longer but then resist bacterially induced mortality, allowing them to survive into a state of end-of-life decrepitude. Thus, changes that slow aging and also prevent an age-associated catastrophe can extend both the youthful and infirm periods of life. Keywords: aging, lifespan, healthspan, daf-2, mortality, IGF-1, pathogenesis

  1. Offering extended use of the combined contraceptive pill: a survey of specialist family planning services

    Directory of Open Access Journals (Sweden)

    Sauer U

    2013-09-01

    Full Text Available Ulrike Sauer,1 Sue Mann,2 Nataliya Brima,3 Judith Stephenson21Reproductive and Sexual Health, Enfield Community Service, Enfield, 2Sexual and Reproductive Health Research Group, Institute for Women’s Health, 3Research Department of Infection and Population Health, University College London, London, UKBackground: The purpose of this study was to determine attitudes to, and provision of, extended regimens for taking the combined oral contraceptive pill (COC by specialist contraception practitioners from three contrasting specialist contraception services in London.Methods: An online cross-sectional survey was administered to all doctors and nurses, who counsel, provide, or prescribe the oral contraceptive pill at each clinic.Results: A total of 105 clinicians received the questionnaire and 67 (64% responded. Only one of three clinics initiated and maintained guidelines for extended COC use. In that service, 60% of staff prescribing COC advised more than 50% of patients regarding alternative COC regimens. In the other two services, this was discussed with 20% and 6% of patients, respectively (P < 0.001. The reasons for prescribing extended use included cyclic headaches, menorrhagia, patient request, menstrual-related cramps, and endometriosis, and did not differ between the three different settings. The most common extended regimens were 63 pills or continuous use until bleeding occurs, followed by a hormone-free interval. Concerns highlighted by providers and patients were “unhealthy not to have a monthly bleed”, “future fertility”, and “breakthrough bleeding”. Such comments highlight the need for further information for providers and patients.Conclusion: There is growing evidence, backed by national guidance, about extended COC use, but routine provision of this information is patchy and varies ten-fold, even within specialist family planning services. Targeted training, use of service guidelines, and implementation research will be

  2. Estimation of adult and neonatal RBC lifespans in anemic neonates using RBCs labeled at several discrete biotin densities.

    Science.gov (United States)

    Kuruvilla, Denison J; Widness, John A; Nalbant, Demet; Schmidt, Robert L; Mock, Donald M; An, Guohua; Veng-Pedersen, Peter

    2017-06-01

    Prior conclusions that autologous neonatal red blood cells (RBC) have substantially shorter lifespans than allogeneic adult RBCs were not based on direct comparison of autologous neonatal vs. allogeneic adult RBCs performed concurrently in the same infant. Biotin labeling of autologous neonatal RBCs and allogeneic adult donor RBCs permits concurrent direct comparison of autologous vs. allogeneic RBC lifespan. RBCs from 15 allogeneic adult donors and from 15 very-low-birth-weight (VLBW) neonates were labeled at separate biotin densities and transfused simultaneously into the 15 neonates. Two mathematical models that account for the RBC differences were employed to estimate lifespans for the two RBC populations. Mean ± SD lifespan for adult allogeneic RBC was 70.1 ± 19.1 d, which is substantially shorter than the 120 d lifespan of both autologous and adult allogeneic RBC in healthy adults. Mean ± SD lifespan for neonatal RBC was 54.2 ± 11.3 d, which is only about 30% shorter than that of the adult allogeneic RBCs. This study provides evidence that extrinsic environmental factors primarily determine RBC survival (e.g., small bore of the capillaries of neonates, rate of oxygenation/deoxygenation cycles) rather than factors intrinsic to RBC.

  3. Extended Irreversible Thermodynamics

    CERN Document Server

    Jou, David

    2010-01-01

    This is the 4th edition of the highly acclaimed monograph on Extended Irreversible Thermodynamics, a theory that goes beyond the classical theory of irreversible processes. In contrast to the classical approach, the basic variables describing the system are complemented by non-equilibrium quantities. The claims made for extended thermodynamics are confirmed by the kinetic theory of gases and statistical mechanics. The book covers a wide spectrum of applications, and also contains a thorough discussion of the foundations and the scope of the current theories on non-equilibrium thermodynamics. For this new edition, the authors critically revised existing material while taking into account the most recent developments in fast moving fields such as heat transport in micro- and nanosystems or fast solidification fronts in materials sciences. Several fundamental chapters have been revisited emphasizing physics and applications over mathematical derivations. Also, fundamental questions on the definition of non-equil...

  4. Extended quantum mechanics

    International Nuclear Information System (INIS)

    Pavel Bona

    2000-01-01

    The work can be considered as an essay on mathematical and conceptual structure of nonrelativistic quantum mechanics which is related here to some other (more general, but also to more special and 'approximative') theories. Quantum mechanics is here primarily reformulated in an equivalent form of a Poisson system on the phase space consisting of density matrices, where the 'observables', as well as 'symmetry generators' are represented by a specific type of real valued (densely defined) functions, namely the usual quantum expectations of corresponding selfjoint operators. It is shown in this paper that inclusion of additional ('nonlinear') symmetry generators (i. e. 'Hamiltonians') into this reformulation of (linear) quantum mechanics leads to a considerable extension of the theory: two kinds of quantum 'mixed states' should be distinguished, and operator - valued functions of density matrices should be used in the role of 'nonlinear observables'. A general framework for physical theories is obtained in this way: By different choices of the sets of 'nonlinear observables' we obtain, as special cases, e.g. classical mechanics on homogeneous spaces of kinematical symmetry groups, standard (linear) quantum mechanics, or nonlinear extensions of quantum mechanics; also various 'quasiclassical approximations' to quantum mechanics are all sub theories of the presented extension of quantum mechanics - a version of the extended quantum mechanics. A general interpretation scheme of extended quantum mechanics extending the usual statistical interpretation of quantum mechanics is also proposed. Eventually, extended quantum mechanics is shown to be (included into) a C * -algebraic (hence linear) quantum theory. Mathematical formulation of these theories is presented. The presentation includes an analysis of problems connected with differentiation on infinite-dimensional manifolds, as well as a solution of some problems connected with the work with only densely defined unbounded

  5. Propelling Extended Objects

    Science.gov (United States)

    Humbert, Richard

    2010-01-01

    A force acting on just part of an extended object (either a solid or a volume of a liquid) can cause all of it to move. That motion is due to the transmission of the force through the object by its material. This paper discusses how the force is distributed to all of the object by a gradient of stress or pressure in it, which creates the local…

  6. Extending Critical Performativity

    DEFF Research Database (Denmark)

    Spicer, André; Alvesson, Mats; Kärreman, Dan

    2016-01-01

    In this article we extend the debate about critical performativity. We begin by outlining the basic tenets of critical performativity and how this has been applied in the study of management and organization. We then address recent critiques of critical performance. We note these arguments suffer...... of public importance; engaging with non-academic groups using dialectical reasoning; scaling up insights through movement building; and propagating deliberation...

  7. Extended Theories of Gravity

    International Nuclear Information System (INIS)

    Capozziello, Salvatore; De Laurentis, Mariafelicia

    2011-01-01

    Extended Theories of Gravity can be considered as a new paradigm to cure shortcomings of General Relativity at infrared and ultraviolet scales. They are an approach that, by preserving the undoubtedly positive results of Einstein’s theory, is aimed to address conceptual and experimental problems recently emerged in astrophysics, cosmology and High Energy Physics. In particular, the goal is to encompass, in a self-consistent scheme, problems like inflation, dark energy, dark matter, large scale structure and, first of all, to give at least an effective description of Quantum Gravity. We review the basic principles that any gravitational theory has to follow. The geometrical interpretation is discussed in a broad perspective in order to highlight the basic assumptions of General Relativity and its possible extensions in the general framework of gauge theories. Principles of such modifications are presented, focusing on specific classes of theories like f(R)-gravity and scalar–tensor gravity in the metric and Palatini approaches. The special role of torsion is also discussed. The conceptual features of these theories are fully explored and attention is paid to the issues of dynamical and conformal equivalence between them considering also the initial value problem. A number of viability criteria are presented considering the post-Newtonian and the post-Minkowskian limits. In particular, we discuss the problems of neutrino oscillations and gravitational waves in extended gravity. Finally, future perspectives of extended gravity are considered with possibility to go beyond a trial and error approach.

  8. Different antibiotic regimens for treating asymptomatic bacteriuria in pregnancy.

    Science.gov (United States)

    Guinto, Valerie T; De Guia, Blanca; Festin, Mario R; Dowswell, Therese

    2010-09-08

    Asymptomatic bacteriuria occurs in 5% to 10% of pregnancies and, if left untreated, can lead to serious complications. To assess which antibiotic is most effective and least harmful as initial treatment for asymptomatic bacteriuria in pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2010) and reference lists of retrieved studies. Randomized controlled trials comparing two antibiotic regimens for treating asymptomatic bacteriuria. Review authors independently screened the studies for inclusion and extracted data. We included five studies involving 1140 women with asymptomatic bacteriuria. We did not perform meta-analysis; each trial examined different antibiotic regimens and so we were not able to pool results. In a study comparing a single dose of fosfomycin trometamol 3 g with a five-day course of cefuroxime, there was no significant difference in persistent infection (risk ratio (RR) 1.36, 95% confidence interval (CI) 0.24 to 7.75), shift to other antibiotics (RR 0.08, 95% CI 0.00 to 1.45), or in allergy or pruritus (RR 2.73, 95% CI 0.11 to 65.24). A comparison of seven-day courses of 400 mg pivmecillinam versus 500 mg ampicillin, both given four times daily, showed no significant difference in persistent infection at two weeks or recurrent infection, but there was an increase in vomiting (RR 4.57, 95% CI 1.40 to 14.90) and women were more likely to stop treatment early with pivmecillinam (RR 8.82, 95% CI 1.16 to 66.95). When cephalexin 1 g versus Miraxid(R) (pivmecillinam 200 mg and pivampicillin 250 mg) were given twice-daily for three days, there was no significant difference in persistent or recurrent infection. A one- versus seven-day course of nitrofurantoin resulted in more persistent infection with the shorter course (RR 1.76, 95% CI 1.29 to 2.40), but no significant difference in symptomatic infection at two weeks, nausea, or preterm birth. Comparing cycloserine with sulphadimidine, no significant differences in

  9. Antirelapse Efficacy of Various Primaquine Regimens for Plasmodium vivax

    Directory of Open Access Journals (Sweden)

    D. D. Rajgor

    2014-01-01

    respectively P=0.004. The relapse rate was 6.89%, 1.55%, 4%, and 3.85% as per the month of recurrence; 8.2%, 2%, 4.58%, and 3.68% P=0.007 as per PCR-RFLP; and 2.73%, 1.47%, 1.55%, and 1.53% as per PCR sequencing for groups A, B, C, and D, respectively. The concordance between methods was low, 45%. Conclusion. The higher recurrence rate in no PQ as compared to PQ groups documents PQ antirelapse activity. Regimens tested were safe. However, probable resistance to PQ warrants continuous monitoring and low concordance and limitations in the methods warrant caution in interpreting.

  10. NAGD regimen for the coma of drug-related overdose.

    Science.gov (United States)

    Rappolt, R T; Gay, G R; Decker, W J; Inaba, D S

    1980-07-01

    A specific arousal therapy with NAGD (Naloxone, Activated Charcoal, Glucagon, Doxapram) is outlined for victims of drug overdose in comatose and semi-comatose states. Several direct benefits accrue if early awakening or lightening of such patients is safely accomplished. There are: 1) elimination of need for prolonged intubation or tracheostomy; 2) patient's ability to tell which drug(s) were taken; 3) excessively frantic and vigorous supportive treatment is obviated; and 4) the overall hospital stay is shortened. The NAGD regimen has been found to effectively, safely, and predictably reverse coma. Therapy consists of: naloxone 0.8 mg to 1.6 mg intravenously; large-bore orogastric tube instillation of 100 gm to 120 gm activated charcoal slurry; glucagon 1 mg to 2 mg intravenously; and, in selected cases, doxapram 1 mg/kg to 2 mg/kg intravenously.

  11. Comparison of antiplatelet regimens in secondary stroke prevention

    DEFF Research Database (Denmark)

    Christiansen, Christine Benn; Pallisgaard, Jannik; Gerds, Thomas Alexander

    2015-01-01

    BACKGROUND: In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke. The purpose of this study was to examine the risk of bleeding or recurrent...... stroke associated with these three treatments. METHODS: Patients who were discharged with first-time ischemic stroke from 2007-2010, with no history of atrial fibrillation were identified from Danish nationwide registries. Hazard ratios (HRs) and 1-year risks of recurrent ischemic stroke and bleeding...... were calculated for each antiplatelet regimen. RESULTS: Among patients discharged after first-time ischemic stroke, 3043 patients were treated with acetylsalicylic acid, 12,295 with a combination of acetylsalicylic acid and dipyridamole, and 3885 with clopidogrel. Adjusted HRs for clopidogrel versus...

  12. Medication regimen complexity in ambulatory older adults with heart failure

    Directory of Open Access Journals (Sweden)

    Cobretti MR

    2017-04-01

    Full Text Available Michael R Cobretti,1 Robert L Page II,2 Sunny A Linnebur,2 Kimberly M Deininger,1 Amrut V Ambardekar,3 JoAnn Lindenfeld,4 Christina L Aquilante1 1Department of Pharmaceutical Sciences, 2Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, 3Division of Cardiology, School of Medicine, University of Colorado, Aurora, CO, 4Advanced Heart Failure and Cardiac Transplant Program, Vanderbilt Heart and Vascular Institute, Nashville, TN, USA Purpose: Heart failure prevalence is increasing in older adults, and polypharmacy is a major problem in this population. We compared medication regimen complexity using the validated patient-level Medication Regimen Complexity Index (pMRCI tool in “young-old” (60–74 years versus “old-old” (75–89 years patients with heart failure. We also compared pMRCI between patients with ischemic cardiomyopathy (ISCM versus nonischemic cardiomyopathy (NISCM.Patients and methods: Medication lists were retrospectively abstracted from the electronic medical records of ambulatory patients aged 60–89 years with heart failure. Medications were categorized into three types – heart failure prescription medications, other prescription medications, and over-the-counter (OTC medications – and scored using the pMRCI tool.Results: The study evaluated 145 patients (n=80 young-old, n=65 old-old, n=85 ISCM, n=60 NISCM, mean age 73±7 years, 64% men, 81% Caucasian. Mean total pMRCI scores (32.1±14.4, range 3–84 and total medication counts (13.3±4.8, range 2–30 were high for the entire cohort, of which 72% of patients were taking eleven or more total medications. Total and subtype pMRCI scores and medication counts did not differ significantly between the young-old and old-old groups, with the exception of OTC medication pMRCI score (6.2±4 young-old versus 7.8±5.8 old-old, P=0.04. With regard to heart failure etiology, total pMRCI scores and medication

  13. Natural dissolved humic substances increase the lifespan and promote transgenerational resistance to salt stress in the cladoceran Moina macrocopa.

    Science.gov (United States)

    Suhett, Albert L; Steinberg, Christian E W; Santangelo, Jayme M; Bozelli, Reinaldo L; Farjalla, Vinicius F

    2011-07-01

    Evidence has accumulated that humic substances (HS) are not inert biogeochemicals. Rather, they cause stress symptoms and may modulate the life history of aquatic organisms. Nevertheless, it is still not clear how HS interact with additional stressors and if their effects are transgenerational. We tested the interactive effects of HS and salt to cladocerans, discussing their consequences for the persistence in fluctuating environments, such as coastal lagoons. We used life-table experiments to test the effects of natural HS from a polyhumic coastal lagoon (0, 5, 10, 20, 50, and 100 mg dissolved organic carbon (DOC) L(-1)) on the life-history of the cladoceran Moina macrocopa. We further tested the effects of HS (10 mg DOC L(-1)), within and across generations, on the resistance of M. macrocopa to salt stress (5.5 g L(-1)). HS at 5-20 mg DOC L(-1) extended the mean lifespan of M. macrocopa by ~30%. HS also increased body length at maturity by ~4% at 5-50 mg DOC L(-1) and stimulated male offspring production at all tested concentrations. Exposure to HS (even maternal only) alleviated the salt-induced reduction of somatic growth. Co-exposure to HS increased body volume by 12-22% relative to salt-only treatments, while pre-exposure to HS increased body volume by 40-56% in treatments with salt presence, when compared to non-pre-exposed animals. HS at environmentally realistic concentrations, by acting as mild chemical stressors, modify crucial life-history traits of M. macrocopa, favoring its persistence in fluctuating environments. Some of the effects of HS are even transgenerational.

  14. Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects.

    Science.gov (United States)

    Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

    2017-06-03

    To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China.

  15. Superiority of Interferon-Free Regimens for Chronic Hepatitis C

    Science.gov (United States)

    Younossi, Zobair M.; Stepanova, Maria; Esteban, Rafael; Jacobson, Ira; Zeuzem, Stefan; Sulkowski, Mark; Henry, Linda; Nader, Fatema; Cable, Rebecca; Afendy, Mariam; Hunt, Sharon

    2017-01-01

    Abstract Patient-reported outcomes (PROs) such as quality of life and work productivity are important for measuring patient's experience. We assessed PROs during and after treatment of hepatitis C virus (HCV) patients. Data were obtained from a phase 3 open label study of sofosbuvir and ribavirin (SOF + RBV) with and without interferon (IFN). Patients completed 4 PRO assessment instruments (SF-36, Functional Assessment of Chronic Illness Therapy—Fatigue, Chronic Liver Disease Questionnaire— HCV, Work Productivity and Activity—Specific Health Problem) before, during, and after treatment. A total of 533 patients with chronic HCV were enrolled; 28.9% treatment-naïve, 23.1% cirrhotic, 219 received IFN + SOF + RBV and 314 received IFN-free SOF + RBV. At baseline, there were no differences in PROs between the IFN-free and IFN-containing treatment arms (all P > 0.05). During treatment, patients receiving IFN + SOF + RBV had a substantial impairment in their PROs (up to −24.4% by treatment week 12, up to −8.3% at week 4 post-treatment). The PRO decrements seen in the SOF + RBV arm were smaller in magnitude (up to −7.1% by treatment week 12), and all returned to baseline or improved by post-treatment week 4. By 12 weeks after treatment cessation, patients who achieved sustained viral response-12 showed some improvement of PRO scores regardless of the regimen (up to +7.1%, P < 0.0001) or previous treatment experience. In multivariate analysis, the use of IFN was independently associated with lower PROs. IFN-based regimens have a profoundly negative impact to PROs. By contrast, the impact of RBV on these PROs is relatively modest. Achieving HCV cure is associated with improvement of most of the PRO scores. PMID:28207507

  16. Effectiveness of a sanguinarine regimen after scaling and root planing.

    Science.gov (United States)

    Tenenbaum, H; Dahan, M; Soell, M

    1999-03-01

    A variety of chemical agents have been evaluated relative to their abilities to inhibit dental plaque and to improve gingival health. Chlorhexidine gluconate is the best known and most widely used member of these agents, but its long-term use is compromised by different side effects, especially extrinsic tooth and tongue staining. Another agent, sanguinarine, which is currently used in both a mouthrinse and toothpaste, leads in some cases only to a transient burning sensation and could be used on a long-term basis. The purpose of this 14-week controlled clinical trial was to assess the effectiveness of a toothpaste and oral rinse containing sanguinaria extract after scaling, root planing and a chlorhexidine regimen. Sixty patients diagnosed as having adult periodontitis received initial periodontal therapy including scaling and root planing, followed by a 2-week oral care regimen which included rinsing with 0.2% chlorhexidine gluconate oral rinse. Upon completion of this 2-week initial therapy phase, patients were randomly assigned to either sanguinarine toothpaste and oral rinse or to control toothpaste and oral rinse without sanguinarine. Plaque (modified Quigley-Hein index) and gingivitis (gingival index) were measured prior to periodontal therapy, at the end of the chlorhexidine phase (2 weeks), and after 8 and 14 weeks. Sanguinarine-containing toothpaste and oral rinse significantly inhibited the redevelopment of gingivitis through the 12 weeks following the chlorhexidine phase compared to the control toothpaste and rinse. Patients in the test group had 26% fewer bleeding sites at 8 weeks, and 32% fewer at 14 weeks, than the control group. Our results support the combined use of chlorhexidine mouthrinse for a short term (2 weeks) followed by sanguinaria mouthrinse and toothpaste up to 3 months in order to optimize the effectiveness of chlorhexidine without side effects. Further studies on the long-term effect of this combination should be established.

  17. Breast Cancer Screening in an Era of Personalized Regimens

    Science.gov (United States)

    Onega, Tracy; Beaber, Elisabeth F.; Sprague, Brian L.; Barlow, William E.; Haas, Jennifer S.; Tosteson, Anna N.A.; Schnall, Mitchell D.; Armstrong, Katrina; Schapira, Marilyn M.; Geller, Berta; Weaver, Donald L.; Conant, Emily F.

    2014-01-01

    Breast cancer screening holds a prominent place in public health, health care delivery, policy, and women’s health care decisions. Several factors are driving shifts in how population-based breast cancer screening is approached, including advanced imaging technologies, health system performance measures, health care reform, concern for “overdiagnosis,” and improved understanding of risk. Maximizing benefits while minimizing the harms of screening requires moving from a “1-size-fits-all” guideline paradigm to more personalized strategies. A refined conceptual model for breast cancer screening is needed to align women’s risks and preferences with screening regimens. A conceptual model of personalized breast cancer screening is presented herein that emphasizes key domains and transitions throughout the screening process, as well as multilevel perspectives. The key domains of screening awareness, detection, diagnosis, and treatment and survivorship are conceptualized to function at the level of the patient, provider, facility, health care system, and population/policy arena. Personalized breast cancer screening can be assessed across these domains with both process and outcome measures. Identifying, evaluating, and monitoring process measures in screening is a focus of a National Cancer Institute initiative entitled PROSPR (Population-based Research Optimizing Screening through Personalized Regimens), which will provide generalizable evidence for a risk-based model of breast cancer screening, The model presented builds on prior breast cancer screening models and may serve to identify new measures to optimize benefits-to-harms tradeoffs in population-based screening, which is a timely goal in the era of health care reform. PMID:24830599

  18. Caloric restriction shortens lifespan through an increase in lipid peroxidation, inflammation and apoptosis in the G93A mouse, an animal model of ALS.

    Directory of Open Access Journals (Sweden)

    Barkha P Patel

    2010-02-01

    Full Text Available Caloric restriction (CR extends lifespan through a reduction in oxidative stress, delays the onset of morbidity and prolongs lifespan. We previously reported that long-term CR hastened clinical onset, disease progression and shortened lifespan, while transiently improving motor performance in G93A mice, a model of amyotrophic lateral sclerosis (ALS that shows increased free radical production. To investigate the long-term CR-induced pathology in G93A mice, we assessed the mitochondrial bioenergetic efficiency and oxidative capacity (CS--citrate synthase content and activity, cytochrome c oxidase--COX activity and protein content of COX subunit-I and IV and UCP3-uncoupling protein 3, oxidative damage (MDA--malondialdehyde and PC--protein carbonyls, antioxidant enzyme capacity (Mn-SOD, Cu/Zn-SOD and catalase, inflammation (TNF-alpha, stress response (Hsp70 and markers of apoptosis (Bax, Bcl-2, caspase 9, cleaved caspase 9 in their skeletal muscle. At age 40 days, G93A mice were divided into two groups: Ad libitum (AL; n = 14; 7 females or CR (n = 13; 6 females, with a diet equal to 60% of AL. COX/CS enzyme activity was lower in CR vs. AL male quadriceps (35%, despite a 2.3-fold higher COX-IV/CS protein content. UCP3 was higher in CR vs. AL females only. MnSOD and Cu/Zn-SOD were higher in CR vs. AL mice and CR vs. AL females. MDA was higher (83% in CR vs. AL red gastrocnemius. Conversely, PC was lower in CR vs. AL red (62% and white (30% gastrocnemius. TNF-alpha was higher (52% in CR vs. AL mice and Hsp70 was lower (62% in CR vs. AL quadriceps. Bax was higher in CR vs. AL mice (41% and CR vs. AL females (52%. Catalase, Bcl-2 and caspases did not differ. We conclude that CR increases lipid peroxidation, inflammation and apoptosis, while decreasing mitochondrial bioenergetic efficiency, protein oxidation and stress response in G93A mice.

  19. Extended Testability Analysis Tool

    Science.gov (United States)

    Melcher, Kevin; Maul, William A.; Fulton, Christopher

    2012-01-01

    The Extended Testability Analysis (ETA) Tool is a software application that supports fault management (FM) by performing testability analyses on the fault propagation model of a given system. Fault management includes the prevention of faults through robust design margins and quality assurance methods, or the mitigation of system failures. Fault management requires an understanding of the system design and operation, potential failure mechanisms within the system, and the propagation of those potential failures through the system. The purpose of the ETA Tool software is to process the testability analysis results from a commercial software program called TEAMS Designer in order to provide a detailed set of diagnostic assessment reports. The ETA Tool is a command-line process with several user-selectable report output options. The ETA Tool also extends the COTS testability analysis and enables variation studies with sensor sensitivity impacts on system diagnostics and component isolation using a single testability output. The ETA Tool can also provide extended analyses from a single set of testability output files. The following analysis reports are available to the user: (1) the Detectability Report provides a breakdown of how each tested failure mode was detected, (2) the Test Utilization Report identifies all the failure modes that each test detects, (3) the Failure Mode Isolation Report demonstrates the system s ability to discriminate between failure modes, (4) the Component Isolation Report demonstrates the system s ability to discriminate between failure modes relative to the components containing the failure modes, (5) the Sensor Sensor Sensitivity Analysis Report shows the diagnostic impact due to loss of sensor information, and (6) the Effect Mapping Report identifies failure modes that result in specified system-level effects.

  20. Extended Wordsearches in Chemistry

    Science.gov (United States)

    Cotton, Simon

    1998-04-01

    Students can be encouraged to develop their factual knowledge by use of puzzles. One strategy described here is the extended wordsearch, where the wordsearch element generates a number of words or phrases from which the answers to a series of questions are selected. The wordsearch can be generated with the aid of computer programs, though in order to make them suitable for students with dyslexia or other learning difficulties, a simpler form is more appropriate. These problems can be employed in a variety of contexts, for example, as topic tests and classroom end-of-lesson fillers. An example is provided in the area of calcium chemistry. Sources of suitable software are listed.

  1. Classical extended superconformal symmetries

    International Nuclear Information System (INIS)

    Viswanathan, R.R.

    1990-10-01

    Super-covariant differential operators are defined in two dimensions which map supersymmetry doublets to other doublets. The possibility of constructing a closed algebra among the fields appearing in such operators is explored. Such an algebra exists for Grassmann-odd differential operators. A representation for these operators in terms of free-field doublets is constructed. An explicit closed algebra involving fields of spin 2 and 5/2, in addition to the stress tensor and the supersymmetry generator, is constructed from such a free-field representation as an example of a non-linear extended superconformal algebra. (author). 9 refs

  2. Development of Foundational Movement Skills: A Conceptual Model for Physical Activity Across the Lifespan.

    Science.gov (United States)

    Hulteen, Ryan M; Morgan, Philip J; Barnett, Lisa M; Stodden, David F; Lubans, David R

    2018-03-09

    Evidence supports a positive association between competence in fundamental movement skills (e.g., kicking, jumping) and physical activity in young people. Whilst important, fundamental movement skills do not reflect the broad diversity of skills utilized in physical activity pursuits across the lifespan. Debate surrounds the question of what are the most salient skills to be learned which facilitate physical activity participation across the lifespan. In this paper, it is proposed that the term 'fundamental movement skills' be replaced with 'foundational movement skills'. The term 'foundational movement skills' better reflects the broad range of movement forms that increase in complexity and specificity and can be applied in a variety of settings. Thus, 'foundational movement skills' includes both traditionally conceptualized 'fundamental' movement skills and other skills (e.g., bodyweight squat, cycling, swimming strokes) that support physical activity engagement across the lifespan. A proposed conceptual model outlines how foundational movement skill competency can provide a direct or indirect pathway, via specialized movement skills, to a lifetime of physical activity. Foundational movement skill development is hypothesized to vary according to culture and/or geographical location. Further, skill development may be hindered or enhanced by physical (i.e., fitness, weight status) and psychological (i.e., perceived competence, self-efficacy) attributes. This conceptual model may advance the application of motor development principles within the public health domain. Additionally, it promotes the continued development of human movement in the context of how it leads to skillful performance and how movement skill development supports and maintains a lifetime of physical activity engagement.

  3. Stability and Change in Risk-Taking Propensity Across the Adult Lifespan

    Science.gov (United States)

    Josef, Anika K.; Richter, David; Samanez-Larkin, Gregory R.; Wagner, Gert G.; Hertwig, Ralph; Mata, Rui

    2016-01-01

    Can risk-taking propensity be thought of as a trait that captures individual differences across domains, measures, and time? Studying stability in risk-taking propensities across the lifespan can help to answer such questions by uncovering parallel, or divergent, trajectories across domains and measures. We contribute to this effort by using data from respondents aged 18 to 85 in the German Socio-Economic Panel Study (SOEP) and by examining (1) differential stability, (2) mean-level differences, and (3) individual-level changes in self-reported general (N = 44,076) and domain-specific (N =11,903) risk-taking propensities across adulthood. In addition, we investigate (4) the correspondence between cross-sectional trajectories of self-report and behavioral measures of social (trust game; N = 646) and nonsocial (monetary gamble; N = 433) risk taking. The results suggest that risk-taking propensity can be understood as a trait with moderate stability. Results show reliable mean-level differences across the lifespan, with risk-taking propensities typically decreasing with age, although significant variation emerges across domains and individuals. Interestingly, the mean-level trajectory for behavioral measures of social and nonsocial risk taking was similar to those obtained from self-reported risk, despite small correlations between task behavior and self-reports. Individual-level analyses suggest a link between changes in risk-taking propensities both across domains and in relation to changes in some of the Big Five personality traits. Overall, these results raise important questions concerning the role of common processes or events that shape the lifespan development of risk-taking across domains as well as other major personality facets. PMID:26820061

  4. Lifespan Development of the Human Brain Revealed by Large-Scale Network Eigen-Entropy

    Directory of Open Access Journals (Sweden)

    Yiming Fan

    2017-09-01

    Full Text Available Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying functional connectivity patterns of the developing and aging brain. Normal brain development is characterized by continuous and significant network evolution through infancy, childhood, and adolescence, following specific maturational patterns. Normal aging is related to some resting state brain networks disruption, which are associated with certain cognitive decline. It is a big challenge to design an integral metric to track connectome evolution patterns across the lifespan, which is to understand the principles of network organization in the human brain. In this study, we first defined a brain network eigen-entropy (NEE based on the energy probability (EP of each brain node. Next, we used the NEE to characterize the lifespan orderness trajectory of the whole-brain functional connectivity of 173 healthy individuals ranging in age from 7 to 85 years. The results revealed that during the lifespan, the whole-brain NEE exhibited a significant non-linear decrease and that the EP distribution shifted from concentration to wide dispersion, implying orderness enhancement of functional connectome over age. Furthermore, brain regions with significant EP changes from the flourishing (7–20 years to the youth period (23–38 years were mainly located in the right prefrontal cortex and basal ganglia, and were involved in emotion regulation and executive function in coordination with the action of the sensory system, implying that self-awareness and voluntary control performance significantly changed during neurodevelopment. However, the changes from the youth period to middle age (40–59 years were located in the mesial temporal lobe and caudate, which are associated with long-term memory, implying that the memory of the human brain begins to decline with age during this period. Overall, the findings suggested that the human connectome

  5. Towards a unified analysis of brain maturation and aging across the entire lifespan: A MRI analysis.

    Science.gov (United States)

    Coupé, Pierrick; Catheline, Gwenaelle; Lanuza, Enrique; Manjón, José Vicente

    2017-11-01

    There is no consensus in literature about lifespan brain maturation and senescence, mainly because previous lifespan studies have been performed on restricted age periods and/or with a limited number of scans, making results instable and their comparison very difficult. Moreover, the use of nonharmonized tools and different volumetric measurements lead to a great discrepancy in reported results. Thanks to the new paradigm of BigData sharing in neuroimaging and the last advances in image processing enabling to process baby as well as elderly scans with the same tool, new insights on brain maturation and aging can be obtained. This study presents brain volume trajectory over the entire lifespan using the largest age range to date (from few months of life to elderly) and one of the largest number of subjects (N = 2,944). First, we found that white matter trajectory based on absolute and normalized volumes follows an inverted U-shape with a maturation peak around middle life. Second, we found that from 1 to 8-10 y there is an absolute gray matter (GM) increase related to body growth followed by a GM decrease. However, when normalized volumes were considered, GM continuously decreases all along the life. Finally, we found that this observation holds for almost all the considered subcortical structures except for amygdala which is rather stable and hippocampus which exhibits an inverted U-shape with a longer maturation period. By revealing the entire brain trajectory picture, a consensus can be drawn since most of the previously discussed discrepancies can be explained. Hum Brain Mapp 38:5501-5518, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Cathy Slack

    2010-03-01

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

  7. The Influence of Parental Psychopathology on Offspring Suicidal Behavior across the Lifespan.

    Directory of Open Access Journals (Sweden)

    Geilson Lima Santana

    Full Text Available Suicide tends to occur in families, and parental psychopathology has been linked to offspring suicidal behaviors. This study explores the influence of parental mental disorders across the lifespan. Data are from the Sao Paulo Megacity Mental Health Survey, a cross-sectional household study with a representative sample of the adult population living in the Sao Paulo Metropolitan Area, Brazil (N=2,942. Survival models examined bivariate and multivariate associations between a range of parental disorders and offspring suicidality. After controlling for comorbidity, number of mental disorders and offspring psychopathology, we found that parental psychopathology influences suicidal behaviors throughout most part of the life cycle, from childhood until young adult years. Generalized anxiety disorder (GAD and antisocial personality were associated with offspring suicidal ideation (OR 1.8 and 1.9, respectively, panic and GAD predicted suicidal attempts (OR 2.3 and 2.7, respectively, and panic was related to the transition from ideation to attempts (OR 2.7. Although noticed in many different stages of the lifespan, this influence is most evident during adolescence. In this period, depression and antisocial personality increased the odds of suicidal ideation (OR 5.1 and 3.2, respectively, and depression, panic disorder, GAD and substance abuse predicted suicidal attempts (OR varying from 1.7 to 3.8. In short, parental disorders characterized by impulsive-aggression and anxiety-agitation were the main predictors of offspring suicidality across the lifespan. This clinically relevant intergenerational transmission of suicide risk was independent of offspring mental disorders, and this underscores the need for a family approach to psychopathology.

  8. Lifespan development of attentiveness in domestic dogs: drawing parallels with humans

    Directory of Open Access Journals (Sweden)

    Lisa Jessica Wallis

    2014-02-01

    Full Text Available Attention is pivotal to consciousness, perception, cognition, and working memory in all mammals, and therefore changes in attention over the lifespan are likely to influence development and aging of all of these functions. Due to their evolutionary and developmental history, the dog is being recognised as an important species for modelling human healthspan, aging and associated diseases. In this study, we investigated the normal lifespan development of attentiveness of pet dogs in naturalistic situations, and compared the resulting cross-sectional developmental trajectories with data from previous studies in humans. We tested a sample of 145 Border collies (six months to 14 years with humans and objects or food as attention attractors, in order to assess their attentional capture, sustained and selective attention and sensorimotor abilities. Our results reveal differences in task relevance in sustained attentional performance when watching a human or a moving object, which may be explained by life-long learning processes involving such stimuli. During task-switching we found that dogs’ selective attention and sensorimotor abilities showed differences between age groups, with performance peaking at middle age. Dogs’ sensorimotor abilities showed a quadratic distribution with age and were correlated with selective attention performance. Our results support the hypothesis that the development and senescence of sensorimotor and attentional control may be fundamentally interrelated. Additionally, attentional capture, sustained attention and sensorimotor control developmental trajectories paralleled those found in humans. Given that the development of attention is similar across humans and dogs, we propose that the same regulatory mechanisms are likely to be present in both species. Finally, this cross-sectional study provides the first description of age group changes in attention over the lifespan of pet dogs.

  9. How a mutation that slows aging can also disproportionately extend end-of-life decrepitude

    Science.gov (United States)

    Podshivalova, Katie; Kerr, Rex A.; Kenyon, Cynthia

    2017-01-01

    Summary The goal of aging research is to extend healthy, active life. For decades, C. elegans daf-2 insulin/IGF-1 receptor mutants have served as a model for extended lifespan and youthfulness. However, a recent report suggested that their longevity is associated with an undesirable phenotype: a disproportionately long period of decrepitude at the end of life. In a human population, such an outcome would be a burden to society, bringing into question the relevance of daf-2 mutants as a model for life extension. However, here we report that, following an extended period of movement, daf-2 mutants survive longer in a decrepit state because of a beneficial trait: they are resistant to colonization of the digestive tract by dietary bacteria, a condition that leads to premature death in wild type and prevents their manifestation of decrepitude. If bacterial colonization is prevented, daf-2 mutants lead chronologically and proportionately healthier lives relative to wild type. PMID:28423308

  10. Non-genetic impact factors on chronological lifespan and stress resistance of baker’s yeast

    Directory of Open Access Journals (Sweden)

    Michael Sauer

    2016-04-01

    Full Text Available Survival under nutrient limitation is an essential feature of microbial cells, and it is defined by the chronological lifespan. We summarize recent findings, illustrating how crucial the choice of the experimental setup is for the interpretation of data in this field. Especially the impact of oxygen supply differs depending on the culture type, highlighting the differences of alternatives like the retentostat to classical batch cultures. Finally the importance of culture conditions on cell aging and survival in biotechnological processes is highlighted.

  11. Overview of osseous tissue findings from the lifespan carcinogenesis studies: From whole animals to molecules

    International Nuclear Information System (INIS)

    Miller, S.C.; Jee, W.S.S.; Bruenger, F.B.; Lloyd, R.D.; Taylor, G.N.

    1991-01-01

    This summary presents some of the findings from the 226 Ra and 239 Pu lifespan carcinogenesis studies in Beagle dogs and discusses these findings relative to the tissue, cellular and molecular biology of osseous tissues. This report attempts to integrate some of the dosimetric and pathological findings with current understanding of the factors that may influence carcinogenesis (and non-carcinogenic pathologies) at the various levels of biological organization. Emphasis is placed on the findings from the 226 Ra study, as this study has recently been completely reviewed and verified

  12. Holistic life-span health outcomes among elite intercollegiate student-athletes.

    Science.gov (United States)

    Sorenson, Shawn C; Romano, Russell; Scholefield, Robin M; Martin, Brandon E; Gordon, James E; Azen, Stanley P; Schroeder, E Todd; Salem, George J

    2014-01-01

    Competitive sports are recognized as having unique health benefits and risks, and the effect of sports on life-span health among elite athletes has received increasing attention. However, supporting scientific data are sparse and do not represent modern athletes. To assess holistic life-span health and health-related quality-of-life (HRQL) among current and former National Collegiate Athletic Association student-athletes (SAs). Cross-sectional study. A large Division I university. Population-based sample of 496 university students and alumni (age 17-84 years), including SAs and an age-matched and sex-matched nonathlete (NA) control group. Participants completed anonymous, self-report questionnaires. We measured the Short-Form 12 (SF-12) physical and mental component HRQL scores and cumulative lifetime experience and relative risk of treatment for joint, cardiopulmonary, and psychosocial health concerns. Older alumni (age 43+ years) SAs reported greater joint health concerns than NAs (larger joint summary scores; P = .04; Cohen d = 0.69; probability of clinically important difference [pCID] = 77%; treatment odds ratio [OR] = 14.0, 95% confidence interval [CI] = 1.6, 126). Joint health for current and younger alumni SAs was similar to that for NAs. Older alumni reported greater cardiopulmonary health concerns than younger alumni (summary score P students (P 99.5%; OR = 7.1, 95% CI = 3.3, 15), but the risk was similar for SAs and NAs. Current SAs demonstrated evidence of better psychosocial health (summary score P = .006; d = -0.52; pCID = 40%) and mental component HRQL (P = .008; d = 0.50; pCID = 48%) versus NAs but similar psychosocial treatment odds (OR = 0.87, 95% CI = 0.39, 1.9). Psychosocial health and mental component HRQL were similar between alumni SAs and NAs. No differences were observed between SAs and NAs in physical component HRQL. The SAs demonstrated significant, clinically meaningful evidence of greater joint health concerns later in life, comparable

  13. Extending juvenility in grasses

    Energy Technology Data Exchange (ETDEWEB)

    Kaeppler, Shawn; de Leon Gatti, Natalia; Foerster, Jillian

    2017-04-11

    The present invention relates to compositions and methods for modulating the juvenile to adult developmental growth transition in plants, such as grasses (e.g. maize). In particular, the invention provides methods for enhancing agronomic properties in plants by modulating expression of GRMZM2G362718, GRMZM2G096016, or homologs thereof. Modulation of expression of one or more additional genes which affect juvenile to adult developmental growth transition such as Glossy15 or Cg1, in conjunction with such modulation of expression is also contemplated. Nucleic acid constructs for down-regulation of GRMZM2G362718 and/or GRMZM2G096016 are also contemplated, as are transgenic plants and products produced there from, that demonstrate altered, such as extended juvenile growth, and display associated phenotypes such as enhanced yield, improved digestibility, and increased disease resistance. Plants described herein may be used, for example, as improved forage or feed crops or in biofuel production.

  14. Extended biorthogonal matrix polynomials

    Directory of Open Access Journals (Sweden)

    Ayman Shehata

    2017-01-01

    Full Text Available The pair of biorthogonal matrix polynomials for commutative matrices were first introduced by Varma and Tasdelen in [22]. The main aim of this paper is to extend the properties of the pair of biorthogonal matrix polynomials of Varma and Tasdelen and certain generating matrix functions, finite series, some matrix recurrence relations, several important properties of matrix differential recurrence relations, biorthogonality relations and matrix differential equation for the pair of biorthogonal matrix polynomials J(A,B n (x, k and K(A,B n (x, k are discussed. For the matrix polynomials J(A,B n (x, k, various families of bilinear and bilateral generating matrix functions are constructed in the sequel.

  15. Extended conformal algebras

    International Nuclear Information System (INIS)

    Goddard, Peter

    1990-01-01

    The algebra of the group of conformal transformations in two dimensions consists of two commuting copies of the Virasoro algebra. In many mathematical and physical contexts, the representations of ν which are relevant satisfy two conditions: they are unitary and they have the ''positive energy'' property that L o is bounded below. In an irreducible unitary representation the central element c takes a fixed real value. In physical contexts, the value of c is a characteristic of a theory. If c < 1, it turns out that the conformal algebra is sufficient to ''solve'' the theory, in the sense of relating the calculation of the infinite set of physically interesting quantities to a finite subset which can be handled in principle. For c ≥ 1, this is no longer the case for the algebra alone and one needs some sort of extended conformal algebra, such as the superconformal algebra. It is these algebras that this paper aims at addressing. (author)

  16. Extended Poisson Exponential Distribution

    Directory of Open Access Journals (Sweden)

    Anum Fatima

    2015-09-01

    Full Text Available A new mixture of Modified Exponential (ME and Poisson distribution has been introduced in this paper. Taking the Maximum of Modified Exponential random variable when the sample size follows a zero truncated Poisson distribution we have derived the new distribution, named as Extended Poisson Exponential distribution. This distribution possesses increasing and decreasing failure rates. The Poisson-Exponential, Modified Exponential and Exponential distributions are special cases of this distribution. We have also investigated some mathematical properties of the distribution along with Information entropies and Order statistics of the distribution. The estimation of parameters has been obtained using the Maximum Likelihood Estimation procedure. Finally we have illustrated a real data application of our distribution.

  17. Extended fuel cycle length

    International Nuclear Information System (INIS)

    Bruyere, M.; Vallee, A.; Collette, C.

    1986-09-01

    Extended fuel cycle length and burnup are currently offered by Framatome and Fragema in order to satisfy the needs of the utilities in terms of fuel cycle cost and of overall systems cost optimization. We intend to point out the consequences of an increased fuel cycle length and burnup on reactor safety, in order to determine whether the bounding safety analyses presented in the Safety Analysis Report are applicable and to evaluate the effect on plant licensing. This paper presents the results of this examination. The first part indicates the consequences of increased fuel cycle length and burnup on the nuclear data used in the bounding accident analyses. In the second part of this paper, the required safety reanalyses are presented and the impact on the safety margins of different fuel management strategies is examined. In addition, systems modifications which can be required are indicated

  18. Effects of transgenic methionine sulfoxide reductase A (MsrA expression on lifespan and age-dependent changes in metabolic function in mice

    Directory of Open Access Journals (Sweden)

    Adam B. Salmon

    2016-12-01

    Full Text Available Mechanisms that preserve and maintain the cellular proteome are associated with long life and healthy aging. Oxidative damage is a significant contributor to perturbation of proteostasis and is dealt with by the cell through regulation of antioxidants, protein degradation, and repair of oxidized amino acids. Methionine sulfoxide reductase A (MsrA repairs oxidation of free- and protein-bound methionine residues through enzymatic reduction and is found in both the cytosol and the mitochondria. Previous studies in Drosophila have shown that increasing expression of MsrA can extend longevity. Here we test the effects of increasing MsrA on longevity and healthy aging in two transgenic mouse models. We show that elevated expression of MsrA targeted specifically to the cytosol reduces the rate of age-related death in female mice when assessed by Gompertz analysis. However, neither cytosolic nor mitochondrial MsrA overexpression extends lifespan when measured by log-rank analysis. In mice with MsrA overexpression targeted to the mitochondria, we see evidence for improved insulin sensitivity in aged female mice. With these and our previous data, we conclude that the increasing MsrA expression in mice has differential effects on aging and healthy aging that are dependent on the target of its subcellular localization.

  19. Fundamental principles of an anti-VEGF treatment regimen: optimal application of intravitreal anti-vascular endothelial growth factor therapy of macular diseases.

    Science.gov (United States)

    Lanzetta, Paolo; Loewenstein, Anat

    2017-07-01

    Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is now considered the gold standard for the treatment of various retinal disorders. As therapy has evolved, so too have the treatment regimens employed by physicians in clinical practice; however, visual outcomes observed in the real world have typically not reflected those reported in clinical trials. Possible reasons for this include a lack of consensus on treatment regimens and a lack of clarity about what the aims of treatment should be. The Vision Academy Steering Committee met to discuss the principles of an ideal treatment regimen, using evidence from the literature to substantiate each point. Literature searches were performed using the MEDLINE/PubMed database (cut-off date: March 2016) and restricted to English-language publications. Studies with fewer than ten patients were excluded from this review. The Steering Committee identified the following four key principles for the ideal treatment regimen for anti-VEGF management of retinal diseases: 1. Maximize and maintain visual acuity (VA) benefits for all patients 2. Decide when to treat next, rather than whether to treat now 3. Titrate the treatment intervals to match patients' needs 4. Treat at each monitoring visit. It is proposed that the adoption of a proactive and more personalized approach in the clinic such as a treat-and-extend regimen will lead to benefits for both the patient and the physician, through a reduction in the associated treatment burden and better utilization of clinic resources. Implementation of the four principles should also lead to better VA outcomes for each patient, with a minimized risk of vision loss.

  20. Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission.

    Science.gov (United States)

    Kumwenda, Newton I; Hoover, Donald R; Mofenson, Lynne M; Thigpen, Michael C; Kafulafula, George; Li, Qing; Mipando, Linda; Nkanaunena, Kondwani; Mebrahtu, Tsedal; Bulterys, Marc; Fowler, Mary Glenn; Taha, Taha E

    2008-07-10

    Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings. Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine) or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth. Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug. Extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants. (ClinicalTrials.gov number, NCT00115648.) 2008 Massachusetts Medical Society

  1. Aggressive regimens for multidrug-resistant tuberculosis decrease all-cause mortality.

    Directory of Open Access Journals (Sweden)

    Carole D Mitnick

    Full Text Available A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen.This study assessed the impact of an aggressive regimen-one containing at least five likely effective drugs, including a fluoroquinolone and injectable-on treatment outcomes in a large MDR-TB patient cohort.This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death.In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7 drugs. Cure or completion was achieved in 66.1% (442 of patients; death occurred in 20.8% (139. Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89, compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93.The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.

  2. Metoprolol succinate extended release/hydrochlorothiazide combination tablets

    Directory of Open Access Journals (Sweden)

    James W Hainer

    2007-07-01

    Full Text Available James W Hainer, Jennifer SuggAstraZeneca LP, Wilmington, DE, USAAbstract: Lowering elevated blood pressure (BP with drug therapy reduces the risk for catastrophic fatal and nonfatal cardiovascular events such as stroke and myocardial infarction. Given the heterogeneity of hypertension as a disease, the marked variability in an individual patient’s BP response, and low response rates with monotherapy, expert groups such as the Joint National Committee (JNC emphasize the value of combination antihypertensive regimens, noting that combinations, usually of different classes, have additive antihypertensive effects. Metoprolol succinate extended-release tablet is a beta-1 (cardio-selective adrenoceptor-blocking agent formulated to provide controlled and predictable release of metoprolol. Hydrochlorothiazide (HCT is a well-established diuretic and antihypertensive agent, which promotes natruresis by acting on the distal renal tubule. The pharmacokinetics, efficacy, and safety/tolerability of the antihypertensive combination tablet, metoprolol extended release hydrochlorothiazide, essentially reflect the well-described independent characteristics of each of the component agents. Not only is the combination product more effective than monotherapy with the individual components but the combination product allows a low-dose multidrug regimen as an alternative to high-dose monotherapy, thereby, minimizing the likelihood of dose-related side-effects.Keywords: antihypertensive, blood pressure, cardiovascular disease, combination product

  3. Dose Response for Radiation Cataractogenesis: A Meta-Regression of Hematopoietic Stem Cell Transplantation Regimens

    Energy Technology Data Exchange (ETDEWEB)

    Hall, Matthew D. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Schultheiss, Timothy E., E-mail: schultheiss@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Smith, David D. [Division of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Nguyen, Khanh H. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Department of Radiation Oncology, Bayhealth Cancer Center, Dover, Delaware (United States); Wong, Jeffrey Y.C. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States)

    2015-01-01

    Purpose/Objective(s): To perform a meta-regression on published data and to model the 5-year probability of cataract development after hematopoietic stem cell transplantation (HSCT) with and without total body irradiation (TBI). Methods and Materials: Eligible studies reporting cataract incidence after HSCT with TBI were identified by a PubMed search. Seventeen publications provided complete information on radiation dose schedule, fractionation, dose rate, and actuarial cataract incidence. Chemotherapy-only regimens were included as zero radiation dose regimens. Multivariate meta-regression with a weighted generalized linear model was used to model the 5-year cataract incidence and contributory factors. Results: Data from 1386 patients in 21 series were included for analysis. TBI was administered to a total dose of 0 to 15.75 Gy with single or fractionated schedules with a dose rate of 0.04 to 0.16 Gy/min. Factors significantly associated with 5-year cataract incidence were dose, dose times dose per fraction (D•dpf), pediatric versus adult status, and the absence of an ophthalmologist as an author. Dose rate, graft versus host disease, steroid use, hyperfractionation, and number of fractions were not significant. Five-fold internal cross-validation showed a model validity of 83% ± 8%. Regression diagnostics showed no evidence of lack-of-fit and no patterns in the studentized residuals. The α/β ratio from the linear quadratic model, estimated as the ratio of the coefficients for dose and D•dpf, was 0.76 Gy (95% confidence interval [CI], 0.05-1.55). The odds ratio for pediatric patients was 2.8 (95% CI, 1.7-4.6) relative to adults. Conclusions: Dose, D•dpf, pediatric status, and regimented follow-up care by an ophthalmologist were predictive of 5-year cataract incidence after HSCT. The low α/β ratio indicates the importance of fractionation in reducing cataracts. Dose rate effects have been observed in single institution studies but not in the

  4. Dose Response for Radiation Cataractogenesis: A Meta-Regression of Hematopoietic Stem Cell Transplantation Regimens

    International Nuclear Information System (INIS)

    Hall, Matthew D.; Schultheiss, Timothy E.; Smith, David D.; Nguyen, Khanh H.; Wong, Jeffrey Y.C.

    2015-01-01

    Purpose/Objective(s): To perform a meta-regression on published data and to model the 5-year probability of cataract development after hematopoietic stem cell transplantation (HSCT) with and without total body irradiation (TBI). Methods and Materials: Eligible studies reporting cataract incidence after HSCT with TBI were identified by a PubMed search. Seventeen publications provided complete information on radiation dose schedule, fractionation, dose rate, and actuarial cataract incidence. Chemotherapy-only regimens were included as zero radiation dose regimens. Multivariate meta-regression with a weighted generalized linear model was used to model the 5-year cataract incidence and contributory factors. Results: Data from 1386 patients in 21 series were included for analysis. TBI was administered to a total dose of 0 to 15.75 Gy with single or fractionated schedules with a dose rate of 0.04 to 0.16 Gy/min. Factors significantly associated with 5-year cataract incidence were dose, dose times dose per fraction (D•dpf), pediatric versus adult status, and the absence of an ophthalmologist as an author. Dose rate, graft versus host disease, steroid use, hyperfractionation, and number of fractions were not significant. Five-fold internal cross-validation showed a model validity of 83% ± 8%. Regression diagnostics showed no evidence of lack-of-fit and no patterns in the studentized residuals. The α/β ratio from the linear quadratic model, estimated as the ratio of the coefficients for dose and D•dpf, was 0.76 Gy (95% confidence interval [CI], 0.05-1.55). The odds ratio for pediatric patients was 2.8 (95% CI, 1.7-4.6) relative to adults. Conclusions: Dose, D•dpf, pediatric status, and regimented follow-up care by an ophthalmologist were predictive of 5-year cataract incidence after HSCT. The low α/β ratio indicates the importance of fractionation in reducing cataracts. Dose rate effects have been observed in single institution studies but not in the

  5. [Influence of dose regimen on gentamycin nephrotoxicity in rats].

    Science.gov (United States)

    Oliveira, V C; Tejos, C R; Hosaka, E M; Andrade, S C; Araújo, M; Vattimo, M F

    2001-06-01

    The acute renal failure (ARF), that still presents a right mortality rate (50%) can be defined as an abrupt decline of the glomerular filtration, resultant of ischemic or toxicity event. The drugs nephrotoxicity is one of the most frequent cause (27%) of ARF and it is suggested that the interval of administration of the drug can interfere in this side effect, however the best administration regimen is not very well established. This study evaluated the renal function of rats that received gentamicin (100 mg/kg) in one dose or in two doses (2 x 50 mg/kg), by intraperitoneal infusion. The results obtained in this research, indicated that the single infusion of gentamicin determined smaller nephrotoxicity by the reduction of serum concentration of this drug in 24 hours, decreasing the intracellular accumulation of this gentamicin, which is one of the main cellular mechanisms of this renal injury. The single dose treatment regime, otherwise, shows advantages not only related to the nephrotoxicity effect, but also it is relevant to the cost and safety, which can be rationable factors in the administration of this drug.

  6. Short-term memory predictions across the lifespan: monitoring span before and after conducting a task.

    Science.gov (United States)

    Bertrand, Julie Marilyne; Moulin, Chris John Anthony; Souchay, Céline

    2017-05-01

    Our objective was to explore metamemory in short-term memory across the lifespan. Five age groups participated in this study: 3 groups of children (4-13 years old), and younger and older adults. We used a three-phase task: prediction-span-postdiction. For prediction and postdiction phases, participants reported with a Yes/No response if they could recall in order a series of images. For the span task, they had to actually recall such series. From 4 years old, children have some ability to monitor their short-term memory and are able to adjust their prediction after experiencing the task. However, accuracy still improves significantly until adolescence. Although the older adults had a lower span, they were as accurate as young adults in their evaluation, suggesting that metamemory is unimpaired for short-term memory tasks in older adults. •We investigate metamemory for short-term memory tasks across the lifespan. •We find younger children cannot accurately predict their span length. •Older adults are accurate in predicting their span length. •People's metamemory accuracy was related to their short-term memory span.

  7. Life-span development of self-esteem and its effects on important life outcomes.

    Science.gov (United States)

    Orth, Ulrich; Robins, Richard W; Widaman, Keith F

    2012-06-01

    We examined the life-span development of self-esteem and tested whether self-esteem influences the development of important life outcomes, including relationship satisfaction, job satisfaction, occupational status, salary, positive and negative affect, depression, and physical health. Data came from the Longitudinal Study of Generations. Analyses were based on 5 assessments across a 12-year period of a sample of 1,824 individuals ages 16 to 97 years. First, growth curve analyses indicated that self-esteem increases from adolescence to middle adulthood, reaches a peak at about age 50 years, and then decreases in old age. Second, cross-lagged regression analyses indicated that self-esteem is best modeled as a cause rather than a consequence of life outcomes. Third, growth curve analyses, with self-esteem as a time-varying covariate, suggested that self-esteem has medium-sized effects on life-span trajectories of affect and depression, small to medium-sized effects on trajectories of relationship and job satisfaction, a very small effect on the trajectory of health, and no effect on the trajectory of occupational status. These findings replicated across 4 generations of participants--children, parents, grandparents, and their great-grandparents. Together, the results suggest that self-esteem has a significant prospective impact on real-world life experiences and that high and low self-esteem are not mere epiphenomena of success and failure in important life domains. 2012 APA, all rights reserved

  8. Radiation-induced increase in lifespan of insects. Implications for theories of mammalian aging and radiosensitivity

    International Nuclear Information System (INIS)

    Ducoff, H.S.

    1976-01-01

    The well-known and well-documented decline in longevity of irradiated mammals contrasts sharply with the increase of lifespan frequently observed in irradiated insects. First reported in 1919 for flour beetles of the genus Tribolium, increase of lifespan has been found following irradiation of adults of many insect taxa, particularly in the order Diptera. The effect may be more pronounced in one sex or the other, or about the same in both, depending on species, and can be observed in sexually segregated as well as in mated populations. This makes it unlikely that the phenomenon can be accounted for by radiation effects on gametogenesis or on mating behaviour. Our recent data on Tribolium castaneum and on T. confusum indicate that the degree of benefit is dose dependent; is markedly reduced as age-at-exposure increases, though still detectable in beetles irradiated six months after emergence; and is probably also induced by exposure to low doses of fast neutrons. The lowered mortality rate of irradiated populations persists for many months, but eventually may exceed that of the controls. Insects are much less dependent than mammals on cell renewal systems, and the Diptera are completely lacking in somatic cell turnover. This suggests that, in mammals as well as in insects, radiation may exert only detrimental effects in rapidly proliferative tissues but a beneficial effect in postmitotic tissues. A mechanism is proposed, based on the hypothesis that repair capacity is regulated in a fashion analogous to that of inducible enzymes. (author)

  9. The effects of oral clefts on hospital use throughout the lifespan

    Directory of Open Access Journals (Sweden)

    Wehby George L

    2012-03-01

    Full Text Available Abstract Background Oral clefts are one of the most common birth defects worldwide. They require multiple healthcare interventions and add significant burden on the health and quality of life of affected individuals. However, not much is known about the long term effects of oral clefts on health and healthcare use of affected individuals. In this study, we evaluate the effects of oral clefts on hospital use throughout the lifespan. Methods We estimate two-part regression models for hospital admission and length of stay for several age groups up to 68 years of age. The study employs unique secondary population-based data from several administrative inpatient, civil registration, demographic and labor market databases for 7,670 individuals born with oral clefts between 1936 and 2002 in Denmark, and 220,113 individuals without oral clefts from a 5% random sample of the total birth population from 1936 to 2002. Results Oral clefts significantly increase hospital use for most ages below 60 years by up to 233% for children ages 0-10 years and 16% for middle age adults. The more severe cleft forms (cleft lip with palate have significantly larger effects on hospitalizations than less severe forms. Conclusions The results suggest that individuals with oral clefts have higher hospitalization risks than the general population throughout most of the lifespan.

  10. Co-chaperone p23 regulates C. elegans Lifespan in Response to Temperature.

    Directory of Open Access Journals (Sweden)

    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.

  11. C30F12.4 influences oogenesis, fat metabolism, and lifespan in C. elegans

    Directory of Open Access Journals (Sweden)

    Lu Wang

    2016-09-01

    Full Text Available ABSTRACT Reproduction, fat metabolism, and longevity are intertwined regulatory axes; recent studies in C. elegans have provided evidence that these processes are directly coupled. However, the mechanisms by which they are coupled and the reproductive signals modulating fat metabolism and lifespan are poorly understood. Here, we find that an oogenesis-enriched gene, c30f12.4, is specifically expressed and located in germ cells and early embryos; when the gene is knocked out, oogenesis is disrupted and brood size is decreased. In addition to the reproductive phenotype, we find that the loss of c30f12.4 alters fat metabolism, resulting in decreased fat storage and smaller lipid droplets. Meanwhile, c30f12.4 mutant worms display a shortened lifespan. Our results highlight an important role for c30f12.4 in regulating reproduction, fat homeostasis, and aging in C. elegans, which helps us to better understand the relationship between these processes.

  12. DOE life-span radiation effects studies at Pacific Northwest Laboratory

    International Nuclear Information System (INIS)

    Thompson, R.C.; Cross, F.T.; Dagle, G.E.; Park, J.F.; Sanders, C.L.

    1986-01-01

    Major life-span radiation effects studies at Pacific Northwest Laboratory fall into three categories: (1) studies with beagle dogs exposed to plutonium compounds via a single inhalation; (2) studies with dogs and rats exposed chronically via inhalation to various combinations and concentrations of radon, radon daughters, and other components of uranium mine atmospheres; and (3) a study in which rats are exposed via single inhalation, in very large numbers, to very low concentrations of 239 PuO 2 . Exposure of beagles currently on study was initiated in 1970 with 239 PuO 2 , in 1973 with 238 PuO 2 , and in 1976 with 239 Pu(NO 3 ) 4 . These experiments involve more than 500 animals, many of them still alive. Experiments seeking to explain the increased incidence of lung cancer in uranium miners have been in progress since 1966. Present emphasis is on studies with rats, in an attempt to define dose-effect relationships at the lowest feasible radon-daughter exposure levels. Our very-low-level experiment with inhaled 239 PuO 2 in rats, with exposures still under way, includes 1000 rats in the control group and 1000 rats in the lowest-exposure group, where life-span lung doses of <5 rads are anticipated

  13. Effect of Spaceflight on the Circadian Rhythm, Lifespan and Gene Expression of Drosophila melanogaster

    Science.gov (United States)

    Xu, Kanyan

    2015-01-01

    Space travelers are reported to experience circadian rhythm disruption during spaceflight. However, how the space environment affects circadian rhythm is yet to be determined. The major focus of this study was to investigate the effect of spaceflight on the Drosophila circadian clock at both the behavioral and molecular level. We used China’s Shenzhou-9 spaceship to carry Drosophila. After 13 days of spaceflight, behavior tests showed that the flies maintained normal locomotor activity rhythm and sleep pattern. The expression level and rhythm of major clock genes were also unaffected. However, expression profiling showed differentially regulated output genes of the circadian clock system between space flown and control flies, suggesting that spaceflight affected the circadian output pathway. We also investigated other physiological effects of spaceflight such as lipid metabolism and lifespan, and searched genes significantly affected by spaceflight using microarray analysis. These results provide new information on the effects of spaceflight on circadian rhythm, lipid metabolism and lifespan. Furthermore, we showed that studying the effect of spaceflight on gene expression using samples collected at different Zeitgeber time could obtain different results, suggesting the importance of appropriate sampling procedures in studies on the effects of spaceflight. PMID:25798821

  14. Effect of spaceflight on the circadian rhythm, lifespan and gene expression of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Lingling Ma

    Full Text Available Space travelers are reported to experience circadian rhythm disruption during spaceflight. However, how the space environment affects circadian rhythm is yet to be determined. The major focus of this study was to investigate the effect of spaceflight on the Drosophila circadian clock at both the behavioral and molecular level. We used China's Shenzhou-9 spaceship to carry Drosophila. After 13 days of spaceflight, behavior tests showed that the flies maintained normal locomotor activity rhythm and sleep pattern. The expression level and rhythm of major clock genes were also unaffected. However, expression profiling showed differentially regulated output genes of the circadian clock system between space flown and control flies, suggesting that spaceflight affected the circadian output pathway. We also investigated other physiological effects of spaceflight such as lipid metabolism and lifespan, and searched genes significantly affected by spaceflight using microarray analysis. These results provide new information on the effects of spaceflight on circadian rhythm, lipid metabolism and lifespan. Furthermore, we showed that studying the effect of spaceflight on gene expression using samples collected at different Zeitgeber time could obtain different results, suggesting the importance of appropriate sampling procedures in studies on the effects of spaceflight.

  15. A prolonged chronological lifespan is an unexpected benefit of the [PSI+] prion in yeast.

    Science.gov (United States)

    Wang, Kai; Melki, Ronald; Kabani, Mehdi

    2017-01-01

    Self-replicating 'proteinaceous infectious particles' or prions are responsible for complex heritable traits in the yeast Saccharomyces cerevisiae. Our current understanding of the biology of yeast prions stems from studies mostly done in the context of actively dividing cells in optimal laboratory growth conditions. Evidence suggest that fungal prions exist in the wild where most cells are in a non-dividing quiescent state, because of imperfect growth conditions, scarcity of nutrients and competition. We know little about the faithful transmission of yeast prions in such conditions and their physiological consequences throughout the lifespan of yeast cells. We addressed this issue for the [PSI+] prion that results from the self-assembly of the translation release factor Sup35p into insoluble fibrillar aggregates. [PSI+] leads to increased nonsense suppression and confers phenotypic plasticity in response to environmental fluctuations. Here, we report that while [PSI+] had little to no effect on growth per se, it dramatically improved the survival of yeast cells in stationary phase. Remarkably, prolonged chronological lifespan persisted even after [PSI+] was cured from the cells, suggesting that prions may facilitate the acquisition of complex new traits. Such an important selective advantage may contribute to the evolutionary conservation of the prion-forming ability of Sup35p orthologues in distantly related yeast species.

  16. A prolonged chronological lifespan is an unexpected benefit of the [PSI+] prion in yeast.

    Directory of Open Access Journals (Sweden)

    Kai Wang

    Full Text Available Self-replicating 'proteinaceous infectious particles' or prions are responsible for complex heritable traits in the yeast Saccharomyces cerevisiae. Our current understanding of the biology of yeast prions stems from studies mostly done in the context of actively dividing cells in optimal laboratory growth conditions. Evidence suggest that fungal prions exist in the wild where most cells are in a non-dividing quiescent state, because of imperfect growth conditions, scarcity of nutrients and competition. We know little about the faithful transmission of yeast prions in such conditions and their physiological consequences throughout the lifespan of yeast cells. We addressed this issue for the [PSI+] prion that results from the self-assembly of the translation release factor Sup35p into insoluble fibrillar aggregates. [PSI+] leads to increased nonsense suppression and confers phenotypic plasticity in response to environmental fluctuations. Here, we report that while [PSI+] had little to no effect on growth per se, it dramatically improved the survival of yeast cells in stationary phase. Remarkably, prolonged chronological lifespan persisted even after [PSI+] was cured from the cells, suggesting that prions may facilitate the acquisition of complex new traits. Such an important selective advantage may contribute to the evolutionary conservation of the prion-forming ability of Sup35p orthologues in distantly related yeast species.

  17. Uneven futures of human lifespans: reckonings from Gompertz mortality rates, climate change, and air pollution.

    Science.gov (United States)

    Finch, Caleb E; Beltrán-Sánchez, Hiram; Crimmins, Eileen M

    2014-01-01

    The past 200 years have enabled remarkable increases in human lifespans through improvements in the living environment that have nearly eliminated infections as a cause of death through improved hygiene, public health, medicine, and nutrition. We argue that the limit to lifespan may be approaching. Since 1997, no one has exceeded Jeanne Calment's record of 122.5 years, despite an exponential increase of centenarians. Moreover, the background mortality may be approaching a lower limit. We calculate from Gompertz coefficients that further increases in longevity to approach a life expectancy of 100 years in 21st century cohorts would require 50% slower mortality rate accelerations, which would be a fundamental change in the rate of human aging. Looking into the 21st century, we see further challenges to health and longevity from the continued burning of fossil fuels that contribute to air pollution as well as global warming. Besides increased heat waves to which elderly are vulnerable, global warming is anticipated to increase ozone levels and facilitate the spread of pathogens. We anticipate continuing socioeconomic disparities in life expectancy.

  18. Beat Synchronization across the Lifespan: Intersection of Development and Musical Experience.

    Directory of Open Access Journals (Sweden)

    Elaine C Thompson

    Full Text Available Rhythmic entrainment, or beat synchronization, provides an opportunity to understand how multiple systems operate together to integrate sensory-motor information. Also, synchronization is an essential component of musical performance that may be enhanced through musical training. Investigations of rhythmic entrainment have revealed a developmental trajectory across the lifespan, showing synchronization improves with age and musical experience. Here, we explore the development and maintenance of synchronization in childhood through older adulthood in a large cohort of participants (N = 145, and also ask how it may be altered by musical experience. We employed a uniform assessment of beat synchronization for all participants and compared performance developmentally and between individuals with and without musical experience. We show that the ability to consistently tap along to a beat improves with age into adulthood, yet in older adulthood tapping performance becomes more variable. Also, from childhood into young adulthood, individuals are able to tap increasingly close to the beat (i.e., asynchronies decline with age, however, this trend reverses from younger into older adulthood. There is a positive association between proportion of life spent playing music and tapping performance, which suggests a link between musical experience and auditory-motor integration. These results are broadly consistent with previous investigations into the development of beat synchronization across the lifespan, and thus complement existing studies and present new insights offered by a different, large cross-sectional sample.

  19. Brain structure across the lifespan: the influence of stress and mood

    Directory of Open Access Journals (Sweden)

    Jose Miguel Soares

    2014-11-01

    Full Text Available Normal brain aging is an inevitable and heterogeneous process characterized by a selective pattern of structural changes. Such heterogeneity arises as a consequence of cumulative effects over the lifespan, including stress and mood effects, which drive different micro- and macro-structural alterations in the brain. Investigating these differences in healthy age-related changes is a major challenge for the comprehension of the cognitive status. Herein we addressed the impact of normal aging, stress, mood and their interplay in the brain gray and white matter structure. We showed the critical impact of age in the white matter volume and how stress and mood influence brain volumetry across the lifespan. Moreover, we found a more profound effect of the interaction of aging/stress/mood on structures located in the left hemisphere. These findings help to clarify some divergent results associated with the aging decline and to enlighten the association between abnormal volumetric alterations and several states that may lead to psychiatric disorders.

  20. Yeast chronological lifespan and proteotoxic stress: is autophagy good or bad?

    Science.gov (United States)

    Sampaio-Marques, Belém; Felgueiras, Carolina; Silva, Alexandra; Rodrigues, Fernando; Ludovico, Paula

    2011-10-01

    Autophagy, a highly conserved proteolytic mechanism of quality control, is essential for the maintenance of metabolic and cellular homoeostasis and for an efficient cellular response to stress. Autophagy declines with aging and is believed to contribute to different aspects of the aging phenotype. The nutrient-sensing pathways PKA (protein kinase A), Sch9 and TOR (target of rapamycin), involved in the regulation of yeast lifespan, also converge on a common targeted process: autophagy. The molecular mechanisms underlying the regulation of autophagy and aging by these signalling pathways in yeast, with special attention to the TOR pathway, are discussed in the present paper. The question of whether or not autophagy could contribute to yeast cell death occurring during CLS (chronological lifespan) is discussed in the light of our findings obtained after autophagy activation promoted by proteotoxic stress. Autophagy progressively increases in cells expressing the aggregation-prone protein α-synuclein and seems to participate in the early cell death and shortening of CLS under these conditions, highlighting that autophagic activity should be maintained below physiological levels to exert its promising anti-aging effects.

  1. Staphylococcus saprophyticus surface-associated protein (Ssp) is associated with lifespan reduction in Caenorhabditis elegans.

    Science.gov (United States)

    Szabados, Florian; Mohner, Amelie; Kleine, Britta; Gatermann, Sören G

    2013-10-01

    Staphylococcal lipases have been proposed as pathogenicity factors. In Staphylococcus saprophyticus the surface-associated protein (Ssp) has been previously characterized as a cell wall-associated true lipase. A S. saprophyticus Δssp::ermB mutant has been described as less virulent in an in vivo model of urinary tract infection compared with its wild-type. This is the first report showing that S. saprophyticus induced a lifespan reduction in Caenorhabditis elegans similar to that of S. aureus RN4220. In two S. saprophyticus Δssp::ermB mutants lifespan reduction in C. elegans was partly abolished. In order to attribute virulence to the lipase activity itself and distinguish this phenomenon from the presence of the Ssp-protein, the conserved active site of the lipase was modified by site-directed ligase-independent mutagenesis and lipase activity-deficient mutants were constructed. These results indicate that the Ssp is associated with pathogenicity in C. elegans and one could speculate that the lipase activity itself is responsible for this virulence.

  2. Riluzole does not improve lifespan or motor function in three ALS mouse models.

    Science.gov (United States)

    Hogg, Marion C; Halang, Luise; Woods, Ina; Coughlan, Karen S; Prehn, Jochen H M

    2017-12-08

    Riluzole is the most widespread therapeutic for treatment of the progressive degenerative disease amyotrophic lateral sclerosis (ALS). Riluzole gained FDA approval in 1995 before the development of ALS mouse models. We assessed riluzole in three transgenic ALS mouse models: the SOD1 G93A model, the TDP-43 A315T model, and the recently developed FUS (1-359) model. Age, sex and litter-matched mice were treated with riluzole (22 mg/kg) in drinking water or vehicle (DMSO) from symptom onset. Lifespan was assessed and motor function tests were carried out twice weekly to determine whether riluzole slowed disease progression. Riluzole treatment had no significant benefit on lifespan in any of the ALS mouse models tested. Riluzole had no significant impact on decline in motor performance in the FUS (1-359) and SOD1 G93A transgenic mice as assessed by Rotarod and stride length analysis. Riluzole is widely prescribed for ALS patients despite questions surrounding its efficacy. Our data suggest that if riluzole was identified as a therapeutic candidate today it would not progress past pre-clinical assessment. This raises questions about the standards used in pre-clinical assessment of therapeutic candidates for the treatment of ALS.

  3. A Modified Prophylactic Regimen for the Prevention of Otitis Externa in Saturation Divers

    Science.gov (United States)

    2013-10-01

    Prophylactic Regimen for the Prevention of Otitis Externa in Saturation Divers Authors: DISTRIBUTION STATEMENT A. Paul C. Algra, LT, MC...May 2012 – May 2013 4. TITLE AND SUBTITLE A Modified Prophylactic Regimen for the Prevention of Otitis Externa in Saturation Divers...SUPPLEMENTARY NOTES 14. ABSTRACT To prevent acute otitis externa (AOE) in the saturation setting and to decrease the side effects

  4. Efficacy of combination of glycolic acid peeling with topical regimen in treatment of melasma.

    Science.gov (United States)

    Chaudhary, Savita; Dayal, Surabhi

    2013-10-01

    Various treatment modalities are available for management of melasma, ranging from topical and oral to chemical peeling, but none is promising alone. Very few studies are available regarding efficacy of combination of topical treatment with chemical peeling. Combination of chemical peeling and topical regimen can be a good treatment modality in the management of this recalcitrant disorder. To assess the efficacy of combination of topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling in the treatment of melasma in Indian patients. Forty Indian patients of moderate to severe epidermal variety melasma were divided into two groups of 20 each. One Group i.e. peel group received topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling and other group i.e. control group received topical regimen (2% hydroquinone, 1% hydrocortisone, 0.05% tretinoin). There was an overall decrease in MASI from baseline in 24 weeks of therapy in both the groups (P value peel with topical regimen showed early and greater improvement than the group which was receiving topical regimen only. This study concluded that combining topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling significantly enhances the therapeutic efficacy of glycolic acid peeling. The combination of glycolic acid peeling with the topical regimen is a highly effective, safe and promising therapeutic option in treatment of melasma.

  5. Population-based evaluation of the effectiveness of two regimens for emergency contraception.

    Science.gov (United States)

    Leung, Vivian W Y; Soon, Judith A; Lynd, Larry D; Marra, Carlo A; Levine, Marc

    2016-06-01

    To estimate and compare the effectiveness of the levonorgestrel and Yuzpe regimens for hormonal emergency contraception in routine clinical practice. A retrospective population-based study included women who accessed emergency contraceptives for immediate use prescribed by community pharmacists in British Columbia, Canada, between December 2000 and December 2002. Linked administrative healthcare data were used to discern the timings of menses, unprotected intercourse, and any pregnancy-related health services. A panel of experts evaluated the compatibility of observed pregnancies with the timing of events. The two regimens were compared with statistical adjustments for potential confounding. Among 7493 women in the cohort, 4470 (59.7%) received levonorgestrel and 3023 (40.3%) the Yuzpe regimen. There were 99 (2.2%) compatible pregnancies in the levonorgestrel group and 94 (3.1%) in the Yuzpe group (P=0.017). The estimated odds ratio for levonorgestrel compared with the Yuzpe regimen after adjusting for potential confounders was 0.64 (95% confidence interval 0.47-0.87). Against an expected pregnancy rate of approximately 5%, the relative and absolute risk reductions were 56.0% and 2.8%, respectively, for levonorgestrel and 36.7% and 1.8% for the Yuzpe regimen. The levonorgestrel regimen is more effective than the Yuzpe regimen in routine use. The data suggest that both regimens are less effective than has been observed in randomized trials. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Birth mass is the key to understanding the negative correlation between lifespan and body size in dogs.

    Science.gov (United States)

    Fan, Rong; Olbricht, Gayla; Baker, Xavior; Hou, Chen

    2016-12-08

    Larger dog breeds live shorter than the smaller ones, opposite of the mass-lifespan relationship observed across mammalian species. Here we use data from 90 dog breeds and a theoretical model based on the first principles of energy conservation and life history tradeoffs to explain the negative correlation between longevity and body size in dogs. We found that the birth/adult mass ratio of dogs scales negatively with adult size, which is different than the weak interspecific scaling in mammals. Using the model, we show that this ratio, as an index of energy required for growth, is the key to understanding why the lifespan of dogs scales negatively with body size. The model also predicts that the difference in mass-specific lifetime metabolic energy usage between dog breeds is proportional to the difference in birth/adult mass ratio. Empirical data on lifespan, body mass, and metabolic scaling law of dogs strongly supports this prediction.

  7. Differential control of ageing and lifespan by isoforms and splice variants across the mTOR network.

    Science.gov (United States)

    Razquin Navas, Patricia; Thedieck, Kathrin

    2017-07-15

    Ageing can be defined as the gradual deterioration of physiological functions, increasing the incidence of age-related disorders and the probability of death. Therefore, the term ageing not only reflects the lifespan of an organism but also refers to progressive functional impairment and disease. The nutrient-sensing kinase mTOR (mammalian target of rapamycin) is a major determinant of ageing. mTOR promotes cell growth and controls central metabolic pathways including protein biosynthesis, autophagy and glucose and lipid homoeostasis. The concept that mTOR has a crucial role in ageing is supported by numerous reports on the lifespan-prolonging effects of the mTOR inhibitor rapamycin in invertebrate and vertebrate model organisms. Dietary restriction increases lifespan and delays ageing phenotypes as well and mTOR has been assigned a major role in this process. This may suggest a causal relationship between the lifespan of an organism and its metabolic phenotype. More than 25 years after mTOR's discovery, a wealth of metabolic and ageing-related effects have been reported. In this review, we cover the current view on the contribution of the different elements of the mTOR signalling network to lifespan and age-related metabolic impairment. We specifically focus on distinct roles of isoforms and splice variants across the mTOR network. The comprehensive analysis of mouse knockout studies targeting these variants does not support a tight correlation between lifespan prolongation and improved metabolic phenotypes and questions the strict causal relationship between them. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  8. Phenotypic analysis of newly isolated short-lifespan Neurospora crassa mutant deficient in a high mobility group box protein.

    Science.gov (United States)

    Yoshihara, Ryouhei; Li, ZhengHao; Ishimori, Keisuke; Kuwabara, Kazuki; Hatakeyama, Shin; Tanaka, Shuuitsu

    2017-08-01

    To elucidate genetic mechanisms affecting the lifespan of the filamentous fungus Neurospora crassa, we attempted to identify a gene of which a defect causes a short-lifespan. By screening a Neurospora knockout library, provided by the Fungal Genetics Stock Center at Kansas State University, several KO strains with a short-lifespan were isolated. FGSC#11693 is one of these, which shows similar phenotypes to known Neurospora short-lifespan mutants as follows: 1) hyphal growth ceases after about 2weeks of cultivation, despite that of the wild-type continuing for over 2years, 2) viability of conidia is lower than that of the wild-type, and 3) high sensitivity to mutagens such as methyl methanesulfonate, ultraviolet radiation, and hydroxyl urea is exhibited. The NCU number of the knocked-out gene in the KO strain is NCU02695, and recovery from the short-lifespan and mutagen sensitivity was achieved by the introduction of this gene from the wild-type. The putative amino acid sequence of the knocked-out gene contains two high mobility group box domains and a mitochondrial localization signal is found at the N-terminal of this sequence. Upon analyzing the subcellular localization of the gene product fused with GFP, GFP signals were detected in mitochondria. From these observations, the gene and KO strain were named mitochondrial high mobility group box protein 1 (MHG1) and mhg1 KO strain, respectively. The amount of mtDNA relative to the nuclear amount was lower in the mhg1 KO strain than in the wild-type. mtDNA aberration was also observed in the mhg1 KO strain. These results suggest that the MHG1 protein plays an important role in the maintenance of mitochondrial DNA, and mitochondrial abnormality caused by mtDNA aberration is responsible for the short-lifespan of the mhg1 KO strain. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Randomized controlled study of a novel triple nitazoxanide (NTZ)-containing therapeutic regimen versus the traditional regimen for eradication of Helicobacter pylori infection.

    Science.gov (United States)

    Shehata, Mona Ah; Talaat, Raghda; Soliman, Samah; Elmesseri, Huda; Soliman, Shaimaa; Abd-Elsalam, Sherief

    2017-10-01

    Helicobacter pylori infection has become more and more resistant to conventional first-line treatment regimens. So, there is a considerable interest in evaluating new antibiotic combinations and regimens. Nitazoxanide is an anti-infective drug with demonstrated activity against protozoa and anaerobic bacteria including H. pylori. This work is designed to evaluate the efficacy and safety of a unique triple nitazoxanide-containing regimen as a treatment regimen in Egyptian patients with H. pylori infection. Two hundred and 24 patients with upper gastrointestinal tract (GIT) dyspeptic symptoms in whom H. pylori -induced GIT disease was confirmed were included in the study. They have been randomized to receive either nitazoxanide 500 mg b.i.d., clarithromycin 500 mg b.i.d., and omeprazole 40 mg twice daily for 14 days or metronidazole 500 mg b.i.d., clarithromycin 500 mg b.i.d., and omeprazole 40  mg twice daily for 14 days. Laboratory evaluation for H. pylori antigen within the stool was performed 6 weeks after cessation of H. pylori treatment regimens to assess the response. The response to treatment was significantly higher in group 1 of nitazoxanide treatment regimen than group 2 of traditional treatment regimen. One hundred and six cases (94.6%) of 112 patients who completed the study in group 1 showed complete cure, while only 63 cases (60.6%) of 104 patients who completed the study in group 2 showed the same response according to per-protocol (PP) analysis (Ppylori. (ClinicalTrials.gov Identifier: NCT02422706). © 2017 John Wiley & Sons Ltd.

  10. Range-extending Zinc-air battery for electric vehicle

    Directory of Open Access Journals (Sweden)

    Steven B. Sherman

    2018-01-01

    Full Text Available A vehicle model is used to evaluate a novel powertrain that is comprised of a dual energy storage system (Dual ESS. The system includes two battery packs with different chemistries and the necessary electronic controls to facilitate their coordination and optimization. Here, a lithium-ion battery pack is used as the primary pack and a Zinc-air battery as the secondary or range-extending pack. Zinc-air batteries are usually considered unsuitable for use in vehicles due to their poor cycle life, but the model demonstrates the feasibility of this technology with an appropriate control strategy, with limited cycling of the range extender pack. The battery pack sizes and the battery control strategy are configured to optimize range, cost and longevity. In simulation the vehicle performance compares favourably to a similar vehicle with a single energy storage system (Single ESS powertrain, travelling up to 75 km further under test conditions. The simulation demonstrates that the Zinc-air battery pack need only cycle 100 times to enjoy a ten-year lifespan. The Zinc-air battery model is based on leading Zinc-air battery research from literature, with some assumptions regarding achievable improvements. Having such a model clarifies the performance requirements of Zinc-air cells and improves the research community's ability to set performance targets for Zinc-air cells.

  11. Shortened β-cell lifespan leads to β-cell deficit in a rodent model of type 2 diabetes

    OpenAIRE

    Manesso, Erica; Toffolo, Gianna M.; Butler, Alexandra E.; Butler, Peter C.; Cobelli, Claudio

    2011-01-01

    Since the fundamental defect in both type 1 and type 2 diabetes is β-cell failure, there is increasing interest in the capacity, if any, for β-cell regeneration. Insights into typical β-cell age and lifespan during normal development and how these are influenced in diabetes is desirable to realistically establish the prospects for β-cell regeneration as means to reverse the deficit in β-cell mass in diabetes. We assessed the mean β-cell age and lifespan by the classical McKendrick-von Foester...

  12. The effect of dosing regimen on the pharmacokinetics of risedronate

    Science.gov (United States)

    Mitchell, David Y; Heise, Mark A; Pallone, Karen A; Clay, Marian E; Nesbitt, John D; Russell, Darrell A; Melson, Chad W

    1999-01-01

    Aims To examine the effect of timing of a risedronate dose relative to food intake on the rate and extent of risedronate absorption following single-dose, oral administration to healthy male and female volunteers. Methods A single-dose, randomized, parallel study design was conducted with volunteers assigned to four treatment groups (31 or 32 subjects per group, 127 subjects total). Each subject was orally administered 30 mg risedronate. Group 1 was fasted for 10 h prior to and 4 h after dosing (fasted group); Groups 2 and 3 were fasted for 10 h and were dosed 1 and 0.5 h, respectively, before a high-fat breakfast; and Group 4 was dosed 2 h after a standard dinner. Blood and urine samples were collected for 168 h after dosing. Pharmacokinetic parameters were estimated by simultaneous analysis of risedronate serum concentration and urinary excretion rate-time data. Results Extent of risedronate absorption (AUC and Ae) was comparable (P = 0.4) in subjects dosed 2 h after dinner and 0.5 h before breakfast; however, a significantly greater extent of absorption occurred when risedronate was given 1 or 4 h prior to a meal (1.4- to 2.3-fold greater). Administration 0.5, 1, or 4 h prior to a meal resulted in a significantly greater rate of absorption (Cmax 2.8-, 3.5-, and 4.1-fold greater, respectively) when compared with 2 h after dinner. Conclusions The comparable extent of risedronate absorption when administered either 0.5–1 h before breakfast or 2 h after an evening meal support previous clinical studies where risedronate was found to have similar effectiveness using these dosing regimens. This flexibility in the timing of risedronate administration may provide patients an alternative means to achieve the desired efficacy while maintaining their normal daily routine. PMID:10583024

  13. Metabolic interrogation as a tool to optimize chemotherapeutic regimens.

    Science.gov (United States)

    Sandulache, Vlad C; Chen, Yunyun; Feng, Lei; William, William N; Skinner, Heath D; Myers, Jeffrey N; Meyn, Raymond E; Li, Jinzhong; Mijiti, Ainiwaer; Bankson, James A; Fuller, Clifton D; Konopleva, Marina Y; Lai, Stephen Y

    2017-03-14

    Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC).We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production. Pt compounds induced an acute dose-dependent, transient drop in lactate generation in vitro, which correlated with effects on DNA damage and cell death. Neutralization of free radical stress abrogated these effects. The magnitude of this effect on lactate production correlated with the differential sensitivity of HNSCC cells to Pt compounds (CDDP vs CBP) and p53-driven Pt chemotherapy resistance. Using dual flank xenograft tumors, we demonstrated that Pt-driven effects on lactate levels correlate with effects on tumor growth delay in a dose-dependent manner and that lactate levels can define the temporal profile of Pt chemotherapy-induced metabolic stress. Lactate interrogation also predicted doxorubicin effects on cell death in both solid tumor (HNSCC) and acute myelogenous leukemia (AML) cell lines.Real-time metabolic interrogation of acute changes in cell and tumor lactate levels reflects chemotherapy effects on DNA damage, cell death and tumor growth delay. We have identified a real-time biomarker of chemotherapy effectiveness which can be used to develop adaptive, iterative and personalized treatment regimens against a variety of solid and hematopoietic malignancies.

  14. The lowest-dose, extended-cycle combined oral contraceptive pill with continuous ethinyl estradiol in the United States: a review of the literature on ethinyl estradiol 20 µg/levonorgestrel 100 µg + ethinyl estradiol 10 µg

    Directory of Open Access Journals (Sweden)

    Sheila Krishnan

    2010-08-01

    Full Text Available Sheila Krishnan, Jessica KileyDepartment of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois, USAAbstract: Extended-cycle oral contraceptives (OCs are increasing in popularity in the United States. A new extended-cycle OC that contains the lowest doses of ethinyl estradiol (EE and levonorgestrel (LNG + continuous EE throughout the cycle is now available. It provides 84 days of a low-dose, combined active pill containing levonorgestrel 100 µg and ethinyl estradiol 20 µg. Instead of 7 days of placebo following the active pills, the regimen delivers 7 days of ethinyl estradiol 10 µg. Existing studies reveal a similar efficacy and adverse effect profile compared with other extended-regimen OCs. Specifically, the unscheduled bleeding profile is similar to other extended-cycle OCs and improves with the increase in the duration of use. Although lower daily doses of hormonal exposure have potential benefit, to our knowledge, there are no published studies indicating that this specific regimen offers a lower incidence of hormone-related side effects or adverse events. In summary, this new extended-cycle OC provides patients a low-dose, extended-regimen OC option without sacrificing efficacy or tolerability.Keywords: continuous regimen, ethinyl estradiol, extended cycle, oral contraceptive

  15. Development of Glutamatergic Proteins in Human Visual Cortex across the Lifespan.

    Science.gov (United States)

    Siu, Caitlin R; Beshara, Simon P; Jones, David G; Murphy, Kathryn M

    2017-06-21

    Traditionally, human primary visual cortex (V1) has been thought to mature within the first few years of life, based on anatomical studies of synapse formation, and establishment of intracortical and intercortical connections. Human vision, however, develops well beyond the first few years. Previously, we found prolonged development of some GABAergic proteins in human V1 (Pinto et al., 2010). Yet as >80% of synapses in V1 are excitatory, it remains unanswered whether the majority of synapses regulating experience-dependent plasticity and receptive field properties develop late, like their inhibitory counterparts. To address this question, we used Western blotting of postmortem tissue from human V1 (12 female, 18 male) covering a range of ages. Then we quantified a set of postsynaptic glutamatergic proteins (PSD-95, GluA2, GluN1, GluN2A, GluN2B), calculated indices for functional pairs that are developmentally regulated (GluA2:GluN1; GluN2A:GluN2B), and determined interindividual variability. We found early loss of GluN1, prolonged development of PSD-95 and GluA2 into late childhood, protracted development of GluN2A until ∼40 years, and dramatic loss of GluN2A in aging. The GluA2:GluN1 index switched at ∼1 year, but the GluN2A:GluN2B index continued to shift until ∼40 year before changing back to GluN2B in aging. We also identified young childhood as a stage of heightened interindividual variability. The changes show that human V1 develops gradually through a series of five orchestrated stages, making it likely that V1 participates in visual development and plasticity across the lifespan. SIGNIFICANCE STATEMENT Anatomical structure of human V1 appears to mature early, but vision changes across the lifespan. This discrepancy has fostered two hypotheses: either other aspects of V1 continue changing, or later changes in visual perception depend on extrastriate areas. Previously, we showed that some GABAergic synaptic proteins change across the lifespan, but most

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

    Science.gov (United States)

    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.

  17. Reduced costs of reproduction in females mediate a shift from a male-biased to a female-biased lifespan in humans

    Science.gov (United States)

    Bolund, Elisabeth; Lummaa, Virpi; Smith, Ken R.; Hanson, Heidi A.; Maklakov, Alexei A.

    2016-01-01

    The causes underlying sex differences in lifespan are strongly debated. While females commonly outlive males in humans, this is generally less pronounced in societies before the demographic transition to low mortality and fertility rates. Life-history theory suggests that reduced reproduction should benefit female lifespan when females pay higher costs of reproduction than males. Using unique longitudinal demographic records on 140,600 reproducing individuals from the Utah Population Database, we demonstrate a shift from male-biased to female-biased adult lifespans in individuals born before versus during the demographic transition. Only women paid a cost of reproduction in terms of shortened post-reproductive lifespan at high parities. Therefore, as fertility decreased over time, female lifespan increased, while male lifespan remained largely stable, supporting the theory that differential costs of reproduction in the two sexes result in the shifting patterns of sex differences in lifespan across human populations. Further, our results have important implications for demographic forecasts in human populations and advance our understanding of lifespan evolution. PMID:27087670

  18. Determining the optimal pelvic floor muscle training regimen for women with stress urinary incontinence.

    Science.gov (United States)

    Dumoulin, Chantale; Glazener, Cathryn; Jenkinson, David

    2011-06-01

    Pelvic floor muscle (PFM) training has received Level-A evidence rating in the treatment of stress urinary incontinence (SUI) in women, based on meta-analysis of numerous randomized control trials (RCTs) and is recommended in many published guidelines. However, the actual regimen of PFM training used varies widely in these RCTs. Hence, to date, the optimal PFM training regimen for achieving continence remains unknown and the following questions persist: how often should women attend PFM training sessions and how many contractions should they perform for maximal effect? Is a regimen of strengthening exercises better than a motor control strategy or functional retraining? Is it better to administer a PFM training regimen to an individual or are group sessions equally effective, or better? Which is better, PFM training by itself or in combination with biofeedback, neuromuscular electrical stimulation, and/or vaginal cones? Should we use improvement or cure as the ultimate outcome to determine which regimen is the best? The questions are endless. As a starting point in our endeavour to identify optimal PFM training regimens, the aim of this study is (a) to review the present evidence in terms of the effectiveness of different PFM training regimens in women with SUI and (b) to discuss the current literature on PFM dysfunction in SUI women, including the up-to-date evidence on skeletal muscle training theory and other factors known to impact on women's participation in and adherence to PFM training. Copyright © 2011 Wiley-Liss, Inc.

  19. Differences in Lipid Measurements by Antiretroviral Regimen Exposure in Cohorts from Asia and Australia

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    Amit C. Achhra

    2012-01-01

    Full Text Available We explored the mean differences in routinely measured lipids (total cholesterol, triglycerides, and high-density lipoprotein cholesterol according to exposure to different combination antiretroviral regimens in Asian (n=2051 and Australian (predominantly Caucasian, n=794 cohorts. The regimen was defined as at least 3 antiretroviral drugs with at least 2 nucleoside-reverse transcriptases (NRTIs and either of at least one protease inhibitor (PI or non-nucleoside-reverse transcriptases (NNRTIs. We categorised cART regimens as: NRTIs as tenofovir based or not; NNRTIs as nevirapine or efavirenz (but not both; and PI as atazanavir based or not. We found that the impact of various antiretroviral regimens on lipids in Asian and Australian cohorts was only different by cohort for total cholesterol (P for interaction between regimen and cohort: 0.05. The differences in total cholesterol were however small and unlikely to be of clinical significance. Overall, tenofovir with nevirapine or atazanavir was associated with the most favorable lipids, while the PI regimens without tenofovir and atazanavir were associated with least favorable lipids. We conclude that the impact of various ART regimens on lipids is largely similar in Asian and Australian cohorts and that the newer drugs such as tenofovir and atazanavir are likely to provide similar benefit in terms of lipid profiles in both populations.

  20. Toxic effect of visible light on Drosophila lifespan depending upon diet protein content.

    Science.gov (United States)

    Shen, Jie; Zhu, Xiang; Gu, Yitian; Zhang, Chiqian; Huang, Jiahong; Qing, Xiao

    2018-03-01

    We investigated the toxic effect of visible light on Drosophila lifespan in both sexes. The toxic effect of ultraviolet (UV) light on organisms is well known. However, the effects of illumination with visible light remain unclear. Here, we found that visible light could be toxic to Drosophila survival, depending on the protein content in diet. In addition, further analysis revealed significant interaction between light and sex, and showed that strong light shortened life span by causing opposite direction changes in mortality rate parameters in females versus males. Our findings suggest that photoageing may be a general phenomenon, and support the theory of sexual antagonistic pleiotropy in aging intervention. The results caution that exposure to visible light could be hazardous to life span and suggest that identification of the underlying mechanism would allow better understanding of aging intervention.

  1. Ovarian Reserve Assessment in Users of Oral Contraception Seeking Fertility Advice on their Reproductive Lifespan

    DEFF Research Database (Denmark)

    Petersen, K. Birch; Hvidman, H. W.; Forman, J. L.

    2016-01-01

    aged 19-46 attending the Fertility Assessment and Counselling Clinic (FACC) from 2011 to 2014 comparing ovarian reserve parameters in OC users with non-OC users. PARTICIPANTS/MATERIALS, SETTING, METHODS: The FAC Clinic was initiated to provide individual fertility assessment and counselling. All women...... follicles sized 5-7 mm (P groups (OC users versus non-users) were comparable regarding age, BMI, smoking and maternal age at menopause. LIMITATIONS, REASON FOR CAUTION......STUDY QUESTION: To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced? SUMMARY ANSWER: Ovarian reserve parameters defined by anti...

  2. Ovarian reserve assessment in users of oral contraception seeking fertility advice on their reproductive lifespan

    DEFF Research Database (Denmark)

    Birch Petersen, K; Hvidman, H W; Forman, J L

    2015-01-01

    aged 19-46 attending the Fertility Assessment and Counselling Clinic (FACC) from 2011 to 2014 comparing ovarian reserve parameters in OC users with non-OC users. PARTICIPANTS/MATERIALS, SETTING, METHODS: The FAC Clinic was initiated to provide individual fertility assessment and counselling. All women...... follicles sized 5-7 mm (P groups (OC users versus non-users) were comparable regarding age, BMI, smoking and maternal age at menopause. LIMITATIONS, REASON FOR CAUTION......STUDY QUESTION: To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced? SUMMARY ANSWER: Ovarian reserve parameters defined by anti...

  3. Explaining sex differences in lifespan in terms of optimal energy allocation in the baboon

    DEFF Research Database (Denmark)

    King, Annette M.; Kirkwood, Thomas B.L.; Shanley, Daryl P.

    2017-01-01

    and other physiological functions, to differ between males and females. We present a model in which females provide all offspring care and males compete for access to reproductive females and in which the partitioning of available energy between the competing fitness-enhancing functions of growth......We provide a quantitative test of the hypothesis that sex role specialization may account for sex differences in lifespan in baboons if such specialization causes the dependency of fitness upon longevity, and consequently the optimal resolution to an energetic trade-off between somatic maintenance...... from differences in the value of somatic maintenance relative to other fitness-enhancing functions in keeping with the disposable soma theory....

  4. Influence of phytoecdysteroids and plants steroidal glycosides on the lifespan and stress resistance of drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Mikhail Vyacheslavovich Shaposhnikov

    2014-12-01

    Full Text Available Background. Elucidation of the molecular mechanisms of effects of the active substances of plant adaptogens is a topical area of researches. Materials and methods. We studied the effect of herbal substances containing phytoecdysteroids (20-hydroxyecdysone and inokosterone of Serratula coronata L. or steroidal glycosides (dioscin and protodioscine of Trigonella foenum-graecum L. on the expression level of stress response genes (genes of heat shock proteins, DNA repair, antioxidant defense and apoptosis, stressresistanse (paraquat, starvation, hyperthermia and lifespan of Drosophila melanogaster. Results. The studied herbal substances upregulated genes of antioxidant defense mechanisms (Sod1, but downregulated the DNA repair (XPF and Rad51 and apoptosis (Hid genes. At the same time herbal substances induced weak adaptogenic and antiaging effects. Conclusion. Our results demonstrate that the herbal substances containing phytoecdysteroids and steroidal glycosides change the expression level of stress-response genes and activate mechanisms of hormesis.

  5. Significance of Building Maintenance Management on Life-Span of Buildings

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    Md Azree Othuman Mydin

    2017-06-01

    Full Text Available The attentions and skills of maintenance are required for the construction of buildings in this twenty-first century. Because much architectural education is still focused on the one-of-a-kind assignment, encouraging the notion of personal fulfillment through leaving a mark for off-springs and obtaining a design award by means of concept drawings. Due to the reason that many building designers (architects, engineers, technicians are not encompassed in the subsequent maintenance of the building, they just regard it as other specialists’ responsibilities. In all likelihood, the building user-to-be has no formal role: the building contractors just fulfill their accountabilities to complete the building in compliance with the contract documents, not to care occupier’s needs and wants. This paper will focus on the important of building maintenance management on the life-span of buildings.

  6. A Cross-Sectional Study of Ageing and Cardiovascular Function over the Baboon Lifespan.

    Directory of Open Access Journals (Sweden)

    Kristen R Yeung

    Full Text Available Ageing is associated with changes at the molecular and cellular level that can alter cardiovascular function and ultimately lead to disease. The baboon is an ideal model for studying ageing due to the similarities in genetic, anatomical, physiological and biochemical characteristics with humans. The aim of this cross-sectional study was to investigate the changes in cardiovascular profile of baboons over the course of their lifespan.Data were collected from 109 healthy baboons (Papio hamadryas at the Australian National Baboon Colony. A linear regression model, adjusting for sex, was used to analyse the association between age and markers of ageing with P 12 years had significantly shorter telomeres when compared to younger (<3 years baboons (P = 0.001.This study is the first to demonstrate that cardiovascular function alters with age in the baboon. This research identifies similarities within cardiovascular parameters between humans and baboon even though the length of life differs between the two species.

  7. Neuromodulation and developmental contextual influences on neural and cognitive plasticity across the lifespan.

    Science.gov (United States)

    Li, Shu-Chen

    2013-11-01

    Behavioral, cognitive, and motivational development entails co-constructive interactions between the environmental and social influences from the developmental context, on the one hand, and the individual's neurobiological inheritance, on the other hand. Key brain networks underlying cognition, emotion, and motivation are innervated by major transmitter systems (e.g., the catecholamines and acetylcholine). Thus, the maturation and senescence of neurotransmitter systems have direct implications for lifespan development. In addition to reviewing evidence on life age differences in dopaminergic modulation and cognitive development, this brief review selectively highlights recent findings on how important influences from the developmental context, such as reward-mediated motivational processes, transgenerational stress transmission, psychosocial stress, and cognitive interventions, may, in part, exert their effects on brain and behavioral development through their effects on neuromodulatory mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Contrasting effects of vocabulary knowledge on temporal and parietal brain structure across lifespan.

    Science.gov (United States)

    Richardson, Fiona M; Thomas, Michael S C; Filippi, Roberto; Harth, Helen; Price, Cathy J

    2010-05-01

    Using behavioral, structural, and functional imaging techniques, we demonstrate contrasting effects of vocabulary knowledge on temporal and parietal brain structure in 47 healthy volunteers who ranged in age from 7 to 73 years. In the left posterior supramarginal gyrus, vocabulary knowledge was positively correlated with gray matter density in teenagers but not adults. This region was not activated during auditory or visual sentence processing, and activation was unrelated to vocabulary skills. Its gray matter density may reflect the use of an explicit learning strategy that links new words to lexical or conceptual equivalents, as used in formal education and second language acquisition. By contrast, in left posterior temporal regions, gray matter as well as auditory and visual sentence activation correlated with vocabulary knowledge throughout lifespan. We propose that these effects reflect the acquisition of vocabulary through context, when new words are learnt within the context of semantically and syntactically related words.

  9. The Developmental Lexicon Project: A behavioral database to investigate visual word recognition across the lifespan.

    Science.gov (United States)

    Schröter, Pauline; Schroeder, Sascha

    2017-12-01

    With the Developmental Lexicon Project (DeveL), we present a large-scale study that was conducted to collect data on visual word recognition in German across the lifespan. A total of 800 children from Grades 1 to 6, as well as two groups of younger and older adults, participated in the study and completed a lexical decision and a naming task. We provide a database for 1,152 German words, comprising behavioral data from seven different stages of reading development, along with sublexical and lexical characteristics for all stimuli. The present article describes our motivation for this project, explains the methods we used to collect the data, and reports analyses on the reliability of our results. In addition, we explored developmental changes in three marker effects in psycholinguistic research: word length, word frequency, and orthographic similarity. The database is available online.

  10. Shortened Lifespan and Lethal Hemorrhage in a Hemophilia A Mouse Model.

    Science.gov (United States)

    Staber, Janice M; Pollpeter, Molly J

    2016-01-01

    Hemophilia A animal models have helped advance our understanding of factor VIII deficiency. Previously, factor VIII deficient mouse models were reported to have a normal life span without spontaneous bleeds. However, the bleeding frequency and survival in these animals has not been thoroughly evaluated. To investigate the survival and lethal bleeding frequency in two strains of E-16 hemophilia A mice. We prospectively studied factor VIII deficient hemizygous affected males (n = 83) and homozygous affected females (n = 55) for survival and bleeding frequency. Animals were evaluated for presence and location of bleeds as potential cause of death. Hemophilia A mice had a median survival of 254 days, which is significantly shortened compared to wild type controls (p hemophilia A mice experienced hemorrhage in several tissues. This previously-underappreciated shortened survival in the hemophilia A murine model provides new outcomes for investigation of therapeutics and also reflects the shortened lifespan of patients if left untreated.

  11. International Organization of Standardization (ISO) and Cambridge Filter Test (CFT) Smoking Regimen Data Comparisons in Tobacco Product Marketing Applications.

    Science.gov (United States)

    Chae, Changyu; Walters, Matthew J; Holman, Matthew R

    2017-07-01

    We investigated the differences in TNCO (tar, nicotine, and carbon monoxide) smoke yields generated under the International Organization of Standardization (ISO) and Federal Trade Commission (FTC) Cambridge Filter Test (CFT) smoking regimens. Twenty-nine commercial cigarette products from the US marketplace were acquired in 2015 and tested by measuring the TNCO smoke yields generated under these 2 nonintense smoking regimens. Data obtained demonstrated a linear relationship between the TNCO yields produced under the 2 smoking regimens (R 2 > 0.99). TNCO yields produced by each product were higher under the CFT smoking regimen than the ISO smoking regimen. We found that tar, nicotine, and carbon monoxide yields were consistently 10% to 13% higher under the CFT smoking regimen than under the ISO smoking regimen. This strong correlation indicates that the 2 smoking regimens can be used to apply a correlation correction to CFT TNCO data and allow its comparison to ISO TNCO data in tobacco product marketing applications.

  12. Developmental changes in GABAergic mechanisms in human visual cortex across the lifespan

    Directory of Open Access Journals (Sweden)

    Joshua G A Pinto

    2010-06-01

    Full Text Available Functional maturation of visual cortex is linked with dynamic changes in synaptic expression of GABAergic mechanisms. These include setting the excitation-inhibition balance required for experience-dependent plasticity, as well as, intracortical inhibition underlying development and aging of receptive field properties. Animal studies have shown developmental regulation of GABAergic mechanisms in visual cortex. In this study, we show for the first time how these mechanisms develop in the human visual cortex across the lifespan. We used Western blot analysis of postmortem tissue from human primary visual cortex (n=30, range: 20 days to 80 years to quantify expression of 8 pre- and post-synaptic GABAergic markers. We quantified the inhibitory modulating cannabinoid receptor (CB1, GABA vesicular transporter (VGAT, GABA synthesizing enzymes (GAD65/GAD67, GABAA receptor anchoring protein (Gephyrin, and GABAA receptor subunits (GABAA∝1, GABAA∝2, GABAA∝3. We found a complex pattern of changes, many of which were prolonged and continued well into into the teen, young adult, and even older adult years. These included a monotonic increase or decrease (GABAA∝1, GABAA∝2, a biphasic increase then decrease (GAD65, Gephyrin, or multiple increases and decreases (VGAT, CB1 across the lifespan. Comparing the balances between the pre- and post-synaptic markers we found 3 main transitions (early childhood, early teen years, aging when there were rapid switches in the composition of the GABAergic signaling system, indicating that functioning of the GABAergic system must change as the visual cortex develops and ages. Furthermore, these results provide key information for translating therapies developed in animal models into effective treatments for amblyopia in humans.

  13. The role of cue detection for prospective memory development across the lifespan.

    Science.gov (United States)

    Hering, Alexandra; Wild-Wall, Nele; Gajewski, Patrick D; Falkenstein, Michael; Kliegel, Matthias; Zinke, Katharina

    2016-12-01

    Behavioral findings suggest an inverted U-shaped pattern of prospective memory development across the lifespan. A key mechanism underlying this development is the ability to detect cues. We examined the influence of cue detection on prospective memory, combining behavioral and electrophysiological measures, in three age groups: adolescents (12-14 years), young (19-28 years), and old adults (66-77 years). Cue detection was manipulated by varying the distinctiveness (i.e., how easy it was to detect the cue based on color) of the prospective memory cue in a semantic judgment ongoing task. Behavioral results supported the pattern of an inverted U-shape with a pronounced prospective memory decrease in old adults. Adolescents and young adults showed a prospective memory specific modulation (larger amplitudes for the cues compared to other trials) already for the N1 component. No such specific modulation was evident in old adults for the early N1 component but only at the later P3b component. Adolescents showed differential modulations of the amplitude also for irrelevant information at the P3b, suggesting less efficient processing. In terms of conceptual implications, present findings underline the importance of cue detection for prospective remembering and reveal different developmental trajectories for cue detection. Our findings suggest that cue detection is not a unitary process but consists of multiple stages corresponding to several ERP components that differentially contribute to prospective memory performance across the lifespan. In adolescents resource allocation for detecting cues seemed successful initially but less efficient at later stages; whereas we found the opposite pattern for old adults. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Changes in Standing and Walking Performance Under Dual-Task Conditions Across the Lifespan.

    Science.gov (United States)

    Ruffieux, Jan; Keller, Martin; Lauber, Benedikt; Taube, Wolfgang

    2015-12-01

    Simultaneous performance of a postural and a concurrent task is rather unproblematic as long as the postural task is executed in an automatic way. However, in situations where postural control requires more central processing, cognitive resources may be exceeded by the addition of an attentionally demanding task. This may lead to interference between the two tasks, manifested in a decreased performance in one or both tasks (dual-task costs). Owing to changes in attentional demands of postural tasks as well as processing capacities across the lifespan, it might be assumed that dual-task costs are particularly pronounced in children and older adults probably leading to a U-shaped pattern for dual-task costs as a function of age. However, these changes in the ability of dual-tasking posture from childhood to old age have not yet been systematically reviewed. Therefore, Web of Science and PubMed databases were searched for studies comparing dual-task performance with one task being standing or walking in healthy groups of young adults and either children or older adults. Seventy-nine studies met inclusion criteria. For older adults, the expected increase in dual-task costs could be confirmed. In contrast, in children there was only feeble evidence for a trend towards enlarged dual-task costs. More good-quality studies comparing dual-task ability in children, young, and, ideally, also older adults within the same paradigm are needed to draw unambiguous conclusions about lifespan development of dual-task performance in postural tasks. There is evidence that, in older adults, dual-task performance can be improved by training. For the other age groups, these effects have yet to be investigated.

  15. Eggs hatching and oncomiracidia lifespan of Dawestrema cycloancistrium, a monogenean parasitic on Arapaima gigas.

    Science.gov (United States)

    Maciel, Patricia Oliveira; Muniz, Celli Rodrigues; Alves, Rosiana Rodrigues

    2017-11-30

    Within the production chain of the Arapaima gigas (pirarucu), sanitary issues are still faced at the fingerling phase regarding infestations by the monogenean Dawestrema cycloancistrium. The present study had the objectives of describing the morphology and development phases of this parasite's eggs and oncomiracidia and determining the hatching time and lifespan of the oncomiracidia at different temperatures. D. cycloancistrium eggs were oval and elongated and had a single long appendage at one pole. The egg development was divided into four phases: embryonated egg, developing egg, larva appearance and ecloded egg. They were found in four forms: isolated in gill filaments; grouped in clusters that were anchored in a gill filament; grouped in clusters and entangled in part of a dead adult monogenean; and grouped in clusters in the environment, fixed to a substrate. Eclosion occurred after 72-96h, with faster development at 29°C and 32°C than at 24°C. The morphology of the oncomiracidia were rounded and elongated. They had two pairs of pigmented eye-spots as well as two ciliated areas located on each lateral part of the body and another on the anterior part of the body. The lifespan of the D. cycloancistrium oncomiracidia were 50 and 58h at 24°C and 27°C, respectively. Larvae were found in the mucus, indicating that the oncomiracidia penetrated the host integument. Understanding reproductive aspects of the D. cycloancistrium monogenean is important for developing specific prophylactic management strategies in aquaculture and providing valuable data for further studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. P300 development across the lifespan: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Rik van Dinteren

    Full Text Available BACKGROUND: The P300 component of the event-related potential is a large positive waveform that can be extracted from the ongoing electroencephalogram using a two-stimuli oddball paradigm, and has been associated with cognitive information processing (e.g. memory, attention, executive function. This paper reviews the development of the auditory P300 across the lifespan. METHODOLOGY/PRINCIPAL FINDINGS: A systematic review and meta-analysis on the P300 was performed including 75 studies (n = 2,811. Scopus was searched for studies using healthy subjects and that reported means of P300 latency and amplitude measured at Pz and mean age. These findings were validated in an independent, existing cross-sectional dataset including 1,572 participants from ages 6-87. Curve-fitting procedures were applied to obtain a model of P300 development across the lifespan. In both studies logarithmic Gaussian models fitted the latency and amplitude data best. The P300 latency and amplitude follow a maturational path from childhood to adolescence, resulting in a period that marks a plateau, after which degenerative effects begin. We were able to determine ages that mark a maximum (in P300 amplitude or trough (in P300 latency segregating maturational from degenerative stages. We found these points of deflection occurred at different ages. CONCLUSIONS/SIGNIFICANCE: It is hypothesized that latency and amplitude index different aspects of brain maturation. The P300 latency possibly indexes neural speed or brain efficiency. The P300 amplitude might index neural power or cognitive resources, which increase with maturation.

  17. Hurst Exponent Analysis of Resting-State fMRI Signal Complexity across the Adult Lifespan

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    Jianxin Dong

    2018-02-01

    Full Text Available Exploring functional information among various brain regions across time enables understanding of healthy aging process and holds great promise for age-related brain disease diagnosis. This paper proposed a method to explore fractal complexity of the resting-state functional magnetic resonance imaging (rs-fMRI signal in the human brain across the adult lifespan using Hurst exponent (HE. We took advantage of the examined rs-fMRI data from 116 adults 19 to 85 years of age (44.3 ± 19.4 years, 49 females from NKI/Rockland sample. Region-wise and voxel-wise analyses were performed to investigate the effects of age, gender, and their interaction on complexity. In region-wise analysis, we found that the healthy aging is accompanied by a loss of complexity in frontal and parietal lobe and increased complexity in insula, limbic, and temporal lobe. Meanwhile, differences in HE between genders were found to be significant in parietal lobe (p = 0.04, corrected. However, there was no interaction between gender and age. In voxel-wise analysis, the significant complexity decrease with aging was found in frontal and parietal lobe, and complexity increase was found in insula, limbic lobe, occipital lobe, and temporal lobe with aging. Meanwhile, differences in HE between genders were found to be significant in frontal, parietal, and limbic lobe. Furthermore, we found age and sex interaction in right parahippocampal gyrus (p = 0.04, corrected. Our findings reveal HE variations of the rs-fMRI signal across the human adult lifespan and show that HE may serve as a new parameter to assess healthy aging process.

  18. Community Resilience throughout the Lifespan--The Potential Contribution of Healthy Elders.

    Science.gov (United States)

    Cohen, Odeya; Geva, Diklah; Lahad, Mooli; Bolotin, Arkady; Leykin, Dima; Goldberg, Avishay; Aharonson-Daniel, Limor

    2016-01-01

    An increase in the exposure and predisposition of civilian populations to disasters has been recorded in the last decades. In major disasters, as demonstrated recently in Nepal (2015) and previously in Haiti (2010), external aid is vital, yet in the first hours after a disaster, communities must usually cope alone with the challenge of providing emergent lifesaving care. Communities therefore need to be prepared to handle emergency situations. Mapping the needs of the populations within their purview is a trying task for decision makers and community leaders. In this context, the elderly are traditionally treated as a susceptible population with special needs. The current study aimed to explore variations in the level of community resilience along the lifespan. The study was conducted in nine small to mid-size towns in Israel between August and November 2011 (N = 885). The Conjoint Community Resiliency Assessment Measure (CCRAM), a validated instrument for community resilience assessment, was used to examine the association between age and community resilience score. Statistical analysis included spline and logistic regression models that explored community resiliency over the lifespan in a way that allowed flexible modeling of the curve without prior constraints. This innovative statistical approach facilitated identification of the ages at which trend changes occurred. The study found a significant rise in community resiliency scores in the age groups of 61-75 years as compared with younger age bands, suggesting that older people in good health may contribute positively to building community resiliency for crisis. Rather than focusing on the growing medical needs and years of dependency associated with increased life expectancy and the resulting climb in the proportion of elders in the population, this paper proposes that active "young at heart" older people can be a valuable resource for their community.

  19. Community Resilience throughout the Lifespan--The Potential Contribution of Healthy Elders.

    Directory of Open Access Journals (Sweden)

    Odeya Cohen

    Full Text Available An increase in the exposure and predisposition of civilian populations to disasters has been recorded in the last decades. In major disasters, as demonstrated recently in Nepal (2015 and previously in Haiti (2010, external aid is vital, yet in the first hours after a disaster, communities must usually cope alone with the challenge of providing emergent lifesaving care. Communities therefore need to be prepared to handle emergency situations. Mapping the needs of the populations within their purview is a trying task for decision makers and community leaders. In this context, the elderly are traditionally treated as a susceptible population with special needs. The current study aimed to explore variations in the level of community resilience along the lifespan. The study was conducted in nine small to mid-size towns in Israel between August and November 2011 (N = 885. The Conjoint Community Resiliency Assessment Measure (CCRAM, a validated instrument for community resilience assessment, was used to examine the association between age and community resilience score. Statistical analysis included spline and logistic regression models that explored community resiliency over the lifespan in a way that allowed flexible modeling of the curve without prior constraints. This innovative statistical approach facilitated identification of the ages at which trend changes occurred. The study found a significant rise in community resiliency scores in the age groups of 61-75 years as compared with younger age bands, suggesting that older people in good health may contribute positively to building community resiliency for crisis. Rather than focusing on the growing medical needs and years of dependency associated with increased life expectancy and the resulting climb in the proportion of elders in the population, this paper proposes that active "young at heart" older people can be a valuable resource for their community.

  20. Arm-Gal4 inheritance influences development and lifespan in Drosophila melanogaster.

    Science.gov (United States)

    Slade, F A; Staveley, B E

    2015-10-19

    The UAS-Gal4 ectopic expression system is a widely used and highly valued tool that allows specific gene expression in Drosophila melanogaster. Yeast transcription factor Gal4 can be directed using D. melanogaster transcriptional control elements, and is often assumed to have little effect on the organism. By evaluation of the consequences of maternal and paternal inheritance of a Gal4 transgene under the transcriptional regulation of armadillo control elements (arm-Gal4), we demonstrated that Gal4 expression could be detrimental to development and longevity. Male progeny expressing arm-Gal4 in the presence of UAS-lacZ transgene had reduced numbers and size of ommatidia, compared to flies expressing UAS-lacZ transgene under the control of other Gal4 transgenes. Aged at 25°C, the median life span of male flies with maternally inherited elav-Gal4 was 70 days, without a responding transgene or with UAS-lacZ. The median life span of maternally inherited arm-Gal4 male flies without a responding transgene was 48 days, and 40 days with the UAS-lacZ transgene. A partial rescue of this phenotype was observed with the expression of UAS-lacZ under paternal arm-Gal4 control, having an average median lifespan of 60 days. This data suggests that arm-Gal4 has detrimental effects on Drosophila development and lifespan that are directly dependent upon parental inheritance, and that the benign responder and reporter gene UAS-lacZ may influence D. melanogaster development. These findings should be taken into consideration during the design and execution of UAS-Gal4 expression experiments.

  1. The cost of mating: influences of life history traits and mating strategies on lifespan in two closely related Yponomeuta species

    NARCIS (Netherlands)

    Bakker, A.C.; Campos Louçã, J.; Roessingh, P.; Menken, S.B.J.

    2011-01-01

    Theory predicts that in monandrous butterfly species males should not invest in a long lifespan because receptive females quickly disappear from the mating population. In polyandrous species, however, it pays for males to invest in longevity, which increases the number of mating opportunities and

  2. NF-κB Immunity in the Brain Determines Fly Lifespan in Healthy Aging and Age-Related Neurodegeneration.

    Science.gov (United States)

    Kounatidis, Ilias; Chtarbanova, Stanislava; Cao, Yang; Hayne, Margaret; Jayanth, Dhruv; Ganetzky, Barry; Ligoxygakis, Petros

    2017-04-25

    During aging, innate immunity progresses to a chronically active state. However, what distinguishes those that "age well" from those developing age-related neurological conditions is unclear. We used Drosophila to explore the cost of immunity in the aging brain. We show that mutations in intracellular negative regulators of the IMD/NF-κB pathway predisposed flies to toxic levels of antimicrobial peptides, resulting in early locomotor defects, extensive neurodegeneration, and reduced lifespan. These phenotypes were rescued when immunity was suppressed in glia. In healthy flies, suppressing immunity in glial cells resulted in increased adipokinetic hormonal signaling with high nutrient levels in later life and an extension of active lifespan. Thus, when levels of IMD/NF-κB deviate from normal, two mechanisms are at play: lower levels derepress an immune-endocrine axis, which mobilizes nutrients, leading to lifespan extension, whereas higher levels increase antimicrobial peptides, causing neurodegeneration. Immunity in the fly brain is therefore a key lifespan determinant. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. NF-κB Immunity in the Brain Determines Fly Lifespan in Healthy Aging and Age-Related Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Ilias Kounatidis

    2017-04-01

    Full Text Available During aging, innate immunity progresses to a chronically active state. However, what distinguishes those that “age well” from those developing age-related neurological conditions is unclear. We used Drosophila to explore the cost of immunity in the aging brain. We show that mutations in intracellular negative regulators of the IMD/NF-κB pathway predisposed flies to toxic levels of antimicrobial peptides, resulting in early locomotor defects, extensive neurodegeneration, and reduced lifespan. These phenotypes were rescued when immunity was suppressed in glia. In healthy flies, suppressing immunity in glial cells resulted in increased adipokinetic hormonal signaling with high nutrient levels in later life and an extension of active lifespan. Thus, when levels of IMD/NF-κB deviate from normal, two mechanisms are at play: lower levels derepress an immune-endocrine axis, which mobilizes nutrients, leading to lifespan extension, whereas higher levels increase antimicrobial peptides, causing neurodegeneration. Immunity in the fly brain is therefore a key lifespan determinant.

  4. Exploring the Processes of Self-Development Encountered by Adult Returners to Higher Education: A Lifespan Psychology Perspective

    Science.gov (United States)

    Mercer, Jenny

    2010-01-01

    Evidence indicates that non-traditional adult returners describe returning to education as a period of self-development and growth. However, lifespan psychology perspectives also show that successful growth and change involves periods of conflict. This paper will explore both the nature of self-development and conflicts experienced by a sample of…

  5. The Lifespan Self-Esteem Scale: Initial Validation of a New Measure of Global Self-Esteem.

    Science.gov (United States)

    Harris, Michelle A; Donnellan, M Brent; Trzesniewski, Kali H

    2018-01-01

    This article introduces the Lifespan Self-Esteem Scale (LSE), a short measure of global self-esteem suitable for populations drawn from across the lifespan. Many existing measures of global self-esteem cannot be used across multiple developmental periods due to changes in item content, response formats, and other scale characteristics. This creates a need for a new lifespan scale so that changes in global self-esteem over time can be studied without confounding maturational changes with alterations in the measure. The LSE is a 4-item measure with a 5-point response format using items inspired by established self-esteem scales. The scale is essentially unidimensional and internally consistent, and it converges with existing self-esteem measures across ages 5 to 93 (N = 2,714). Thus, the LSE appears to be a useful measure of global self-esteem suitable for use across the lifespan as well as contexts where a short measure is desirable, such as populations with short attention spans or large projects assessing multiple constructs. Moreover, the LSE is one of the first global self-esteem scales to be validated for children younger than age 8, which provides the opportunity to broaden the field to include research on early formation and development of global self-esteem, an area that has previously been limited.

  6. How changes in subjective general health predict future time perspective, and development and generativity motives over the lifespan

    NARCIS (Netherlands)

    Kooij, D.T.A.M.; Voorde, F.C. van de

    2011-01-01

    In this study, we used the lifespan theories of selection optimization and compensation (SOC) and the socio-emotional selectivity theory (SST) to integrate the disengagement and activity perspectives on aging and to explain intra-individual changes in work motivation. A two-wave longitudinal survey

  7. Differential control of ageing and lifespan by isoforms and splice variants across the mTOR network

    NARCIS (Netherlands)

    Razquin Navas, Patricia; Thedieck, Kathrin

    2017-01-01

    Ageing can be defined as the gradual deterioration of physiological functions, increasing the incidence of age-related disorders and the probability of death. Therefore, the term ageing not only reflects the lifespan of an organism but also refers to progressive functional impairment and disease.

  8. The protein kinase MBK-1 contributes to lifespan extension in daf-2 mutant and germline-deficient Caenorhabditis elegans.

    Science.gov (United States)

    Mack, Hildegard I D; Zhang, Peichuan; Fonslow, Bryan R; Yates, John R

    2017-05-25

    In Caenorhabditis elegans , reduction of insulin/IGF-1 like signaling and loss of germline stem cells both increase lifespan by activating the conserved transcription factor DAF-16 (FOXO). While the mechanisms that regulate DAF-16 nuclear localization in response to insulin/IGF-1 like signaling are well characterized, the molecular pathways that act in parallel to regulate DAF-16 transcriptional activity, and the pathways that couple DAF-16 activity to germline status, are not fully understood at present. Here, we report that inactivation of MBK-1, the C. elegans ortholog of the human FOXO1-kinase DYRK1A substantially shortens the prolonged lifespan of daf-2 and glp-1 mutant animals while decreasing wild-type lifespan to a lesser extent. On the other hand, lifespan-reduction by mutation of the MBK-1-related kinase HPK-1 was not preferential for long-lived mutants. Interestingly, mbk-1 loss still allowed for DAF-16 nuclear accumulation but reduced expression of certain DAF-16 target genes in germline-less, but not in daf-2 mutant animals. These findings indicate that mbk-1 and daf-16 functionally interact in the germline- but not in the daf-2 pathway. Together, our data suggest mbk-1 as a novel regulator of C. elegans longevity upon both, germline ablation and DAF-2 inhibition, and provide evidence for mbk-1 regulating DAF-16 activity in germline-deficient animals.

  9. Resistance to oxidative stress induced by paraquat correlates well with both decreased and increased lifespan in Drosophila melanogaster

    NARCIS (Netherlands)

    Vermeulen, CJ; Van De Zande, L; Bijlsma, R

    2005-01-01

    There is increasing support for the notion that genetic variation for lifespan, both within and between species, is correlated with variation in the efficiency of the free radical scavenging system and the ability to withstand oxidative stress. In Drosophila, resistance to dietary paraquat, a free

  10. Changes in dopamine levels and locomotor activity in response to selection on virgin lifespan in Drosophila melanogaster

    NARCIS (Netherlands)

    Vermeulen, C.J.; Cremers, T.I.F.H.; Westerink, B.H.C.; van de Zande, L.; Bijlsma, R.

    Among various other mechanisms, genetic differences in the production of reactive oxygen species are thought to underlie genetic variation for longevity. Here we report on possible changes in ROS production related processes in response to selection for divergent virgin lifespan in Drosophila. The

  11. Priority-Setting for Novel Drug Regimens to Treat Tuberculosis: An Epidemiologic Model.

    Directory of Open Access Journals (Sweden)

    Emily A Kendall

    2017-01-01

    Full Text Available Novel drug regimens are needed for tuberculosis (TB treatment. New regimens aim to improve on characteristics such as duration, efficacy, and safety profile, but no single regimen is likely to be ideal in all respects. By linking these regimen characteristics to a novel regimen's ability to reduce TB incidence and mortality, we sought to prioritize regimen characteristics from a population-level perspective.We developed a dynamic transmission model of multi-strain TB epidemics in hypothetical populations reflective of the epidemiological situations in India (primary analysis, South Africa, the Philippines, and Brazil. We modeled the introduction of various novel rifampicin-susceptible (RS or rifampicin-resistant (RR TB regimens that differed on six characteristics, identified in consultation with a team of global experts: (1 efficacy, (2 duration, (3 ease of adherence, (4 medical contraindications, (5 barrier to resistance, and (6 baseline prevalence of resistance to the novel regimen. We compared scale-up of these regimens to a baseline reflective of continued standard of care. For our primary analysis situated in India, our model generated baseline TB incidence and mortality of 157 (95% uncertainty range [UR]: 113-187 and 16 (95% UR: 9-23 per 100,000 per year at the time of novel regimen introduction and RR TB incidence and mortality of 6 (95% UR: 4-10 and 0.6 (95% UR: 0.3-1.1 per 100,000 per year. An optimal RS TB regimen was projected to reduce 10-y TB incidence and mortality in the India-like scenario by 12% (95% UR: 6%-20% and 11% (95% UR: 6%-20%, respectively, compared to current-care projections. An optimal RR TB regimen reduced RR TB incidence by an estimated 32% (95% UR: 18%-46% and RR TB mortality by 30% (95% UR: 18%-44%. Efficacy was the greatest determinant of impact; compared to a novel regimen meeting all minimal targets only, increasing RS TB treatment efficacy from 94% to 99% reduced TB mortality by 6% (95% UR: 1%-13%, half the

  12. Irreducibility conditions for extended superfields

    International Nuclear Information System (INIS)

    Sokatchev, E.

    1981-05-01

    The irreducible supermultiplets contained in an extended superfield are presented as sets of covariant derivatives of the superfield. Differential irreducibility constraints are easily obtained from this decomposition. (author)

  13. Uncoupling of oxidative stress resistance and lifespan in long-lived isp-1 mitochondrial mutants in Caenorhabditis elegans.

    Science.gov (United States)

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

    2017-07-01

    Mutations affecting components of the mitochondrial electron transport chain have been shown to increase lifespan in multiple species including the worm Caenorhabditis elegans. While it was originally proposed that decreased generation of reactive oxygen species (ROS) resulting from lower rates of electron transport could account for the observed increase in lifespan, recent evidence indicates that ROS levels are increased in at least some of these long-lived mitochondrial mutants. Here, we show that the long-lived mitochondrial mutant isp-1 worms have increased resistance to oxidative stress. Our results suggest that elevated ROS levels in isp-1 worms cause the activation of multiple stress-response pathways including the mitochondrial unfolded protein response, the SKN-1-mediated stress response, and the hypoxia response. In addition, these worms have increased expression of specific antioxidant enzymes, including a marked upregulation of the inducible superoxide dismutase genes sod-3 and sod-5. Examining the contribution of sod-3 and sod-5 to the oxidative stress resistance in isp-1 worms revealed that loss of either of these genes increased resistance to oxidative stress, but not other forms of stress. Deletion of sod-3 or sod-5 decreased the lifespan of isp-1 worms and further exacerbated their slow physiologic rates. Thus, while deletion of sod-3 and sod-5 genes has little impact on stress resistance, physiologic rates or lifespan in wild-type worms, these genes are required for the longevity of isp-1 worms. Overall, this work shows that the increased resistance to oxidative stress in isp-1 worms does not account for their longevity, and that resistance to oxidative stress can be experimentally dissociated from lifespan. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Large and stable reversible lithium-ion storages from mesoporous SnO2 nanosheets with ultralong lifespan over 1000 cycles

    Science.gov (United States)

    Zhang, Xiao; Jiang, Bin; Guo, Jinxue; Xie, Yaping; Tang, Lin

    2014-12-01

    The major challenge to promote the commercialization of SnO2 anode materials is to construct unique structures and/or composites that could alleviate the volume effect and extend the lifespan. This study develops an efficient synthetic solution for the preparation of mesoporous SnO2 nanosheets, which involves an evaporation-induced selfassembly process and the following thermal treatment. Surfactant F127 is used as the soft template to form abundant cores. The as-prepared sample intrinsically inherits flexible sheet-like structure and porous features, as characterized with XRD, SEM, TEM and BET techniques. Based on these combining structural benefits, the sample is utilized as anode materials for lithium-ion batteries and exhibits excellent Li+ storage performance such as large and stable reversible capacity, good rate capability, and especially the outstanding durable cycling life of over 1000 cycles, which meets the demands of practical applications. The structural changes of SnO2 nanosheets are observed from the decomposed electrodes after different electrochemical cycles. Moreover, this synthesis strategy may offer an alternative and universal approach for synthesis of other transitional metal oxides or their binary composites as high-performance anode materials for lithium-ion batteries.

  15. Plasma digoxin concentrations and urinary excretion during a 'simpler' regimen of infant digitalization.

    Science.gov (United States)

    Savage, M O; Hibble, A G; Pickering, D

    1975-01-01

    We have measured the plasma concentrations in sick neonates and infants being administered digoxin by a safer regimen. In the presence of normal renal function the plasma concentrations appear to be satisfactory. PMID:1103751

  16. Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen

    DEFF Research Database (Denmark)

    Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    PURPOSE: The present work reports rationalized development and characterization of solidified self-nanoemulsifying drug delivery system for oral delivery of combinatorial (tamoxifen and quercetin) therapeutic regimen. METHODS: Suitable oil for the preparation of liquid SNEDDS was selected based...

  17. Extending cosmology: the metric approach

    OpenAIRE

    Mendoza, S.

    2012-01-01

    Comment: 2012, Extending Cosmology: The Metric Approach, Open Questions in Cosmology; Review article for an Intech "Open questions in cosmology" book chapter (19 pages, 3 figures). Available from: http://www.intechopen.com/books/open-questions-in-cosmology/extending-cosmology-the-metric-approach

  18. Extended cognition and epistemic luck

    NARCIS (Netherlands)

    Carter, J.A.

    2013-01-01

    When extended cognition is extended into mainstream epistemology, an awkward tension arises when considering cases of environmental epistemic luck. Surprisingly, it is not at all clear how the mainstream verdict that agents lack knowledge in cases of environmental luck can be reconciled with

  19. Identification of a sustainable two-plant diet that effectively prevents age-related metabolic syndrome and extends lifespan in aged mice.

    Science.gov (United States)

    Li, Xiang-Yong; Liu, Ying-Hua; Wang, Bin; Chen, Chih-Yu; Zhang, Hong-Man; Kang, Jing X

    2018-01-01

    The current system of food production is linked to both the increasing prevalence of chronic disease and the deterioration of the environment, and thereby calls for novel ways of producing nutritious foods in a sustainable manner. In the "longevity village" of Bama, China, we have identified two plant foods, hemp seed and bitter vegetable (Sonchus oleraceus), that are commonly consumed by its residents and grow abundantly in unfarmed land without fertilizers or pesticides. Here, we show that a diet composed of these two foods (the "HB diet") provides a sufficient variety of nutrients and confers significant health benefits. Aged mice allowed ad libitum access to the HB diet not only had longer life spans and improved cognitive function but were also protected against age-related metabolic syndrome, fatty liver, gut dysbiosis and chronic inflammation compared to aged mice fed a control Western diet. Furthermore, longevity-related genes (including 5'adenosine monophosphate-activated protein kinase, sirtuin 1, nuclear respiratory factor 1 and forkhead box O3) were significantly up-regulated, while aging-related genes (including mammalian target of rapamycin and nuclear factor kappa B) were down-regulated. These results demonstrate that the HB diet is capable of promoting health and longevity, and present a sustainable source of healthy foods that can help control the prevalence of chronic diseases and reduce agricultural impact on the environment. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Placebo HAART Regimen as a Method for Teaching Medication Adherence Issues to Students

    OpenAIRE

    Sutton, Eliza L; Transue, Emily R; Comes E, Susan; Paauw, Douglas S

    2005-01-01

    Placebo medication regimens may help educate students about adherence issues. In this randomized trial, 23 third-year medical students took a 2-week placebo regimen mimicking highly active antiretroviral therapy (HAART) during their medicine clerkship; 15 students served as controls. Although no effect was demonstrated from this intervention on an evaluation instrument examining attitudes and beliefs about medication nonadherence, all 23 student-subjects agreed in postintervention interviews ...