Animal models of aging research: implications for human aging and age-related diseases.

PubMed

Mitchell, Sarah J; Scheibye-Knudsen, Morten; Longo, Dan L; de Cabo, Rafael

2015-01-01

Aging is characterized by an increasing morbidity and functional decline that eventually results in the death of an organism. Aging is the largest risk factor for numerous human diseases, and understanding the aging process may thereby facilitate the development of new treatments for age-associated diseases. The use of humans in aging research is complicated by many factors, including ethical issues; environmental and social factors; and perhaps most importantly, their long natural life span. Although cellular models of human disease provide valuable mechanistic information, they are limited in that they may not replicate the in vivo biology. Almost all organisms age, and thus animal models can be useful for studying aging. Herein, we review some of the major models currently used in aging research and discuss their benefits and pitfalls, including interventions known to extend life span and health span. Finally, we conclude by discussing the future of animal models in aging research.

GENOMIC BASIS OF AGING AND LIFE HISTORY EVOLUTION IN DROSOPHILA MELANOGASTER

PubMed Central

Remolina, Silvia C.; Chang, Peter L.; Leips, Jeff; Nuzhdin, Sergey V.; Hughes, Kimberly A.

2015-01-01

Natural diversity in aging and other life history patterns is a hallmark of organismal variation. Related species, populations, and individuals within populations show genetically based variation in life span and other aspects of age-related performance. Population differences are especially informative because these differences can be large relative to within-population variation and because they occur in organisms with otherwise similar genomes. We used experimental evolution to produce populations divergent for life span and late-age fertility and then used deep genome sequencing to detect sequence variants with nucleotide-level resolution. Several genes and genome regions showed strong signatures of selection, and the same regions were implicated in independent comparisons, suggesting that the same alleles were selected in replicate lines. Genes related to oogenesis, immunity, and protein degradation were implicated as important modifiers of late-life performance. Expression profiling and functional annotation narrowed the list of strong candidate genes to 38, most of which are novel candidates for regulating aging. Life span and early-age fecundity were negatively correlated among populations; therefore the alleles we identified also are candidate regulators of a major life-history trade-off. More generally, we argue that hitchhiking mapping can be a powerful tool for uncovering the molecular bases of quantitative genetic variation. PMID:23106705

Life-span development of self-esteem and its effects on important life outcomes.

PubMed

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

Short-lived infected cells support virus replication in sooty mangabeys naturally infected with simian immunodeficiency virus: implications for AIDS pathogenesis.

PubMed

Gordon, Shari N; Dunham, Richard M; Engram, Jessica C; Estes, Jacob; Wang, Zichun; Klatt, Nichole R; Paiardini, Mirko; Pandrea, Ivona V; Apetrei, Cristian; Sodora, Donald L; Lee, Ha Youn; Haase, Ashley T; Miller, Michael D; Kaur, Amitinder; Staprans, Silvija I; Perelson, Alan S; Feinberg, Mark B; Silvestri, Guido

2008-04-01

Sooty mangabeys (SMs) naturally infected with simian immunodeficiency virus (SIV) do not develop AIDS despite high levels of virus replication. At present, the mechanisms underlying this disease resistance are poorly understood. Here we tested the hypothesis that SIV-infected SMs avoid immunodeficiency as a result of virus replication occurring in infected cells that live significantly longer than human immunodeficiency virus (HIV)-infected human cells. To this end, we treated six SIV-infected SMs with potent antiretroviral therapy (ART) and longitudinally measured the decline in plasma viremia. We applied the same mathematical models used in HIV-infected individuals and observed that SMs naturally infected with SIV also present a two-phase decay of viremia following ART, with the bulk (92 to 99%) of virus replication sustained by short-lived cells (average life span, 1.06 days), and only 1 to 8% occurring in longer-lived cells. In addition, we observed that ART had a limited impact on CD4(+) T cells and the prevailing level of T-cell activation and proliferation in SIV-infected SMs. Collectively, these results suggest that in SIV-infected SMs, similar to HIV type 1-infected humans, short-lived activated CD4(+) T cells, rather than macrophages, are the main source of virus production. These findings indicate that a short in vivo life span of infected cells is a common feature of both pathogenic and nonpathogenic primate lentivirus infections and support a model for AIDS pathogenesis whereby the direct killing of infected cells by HIV is not the main determinant of disease progression.

Short-Lived Infected Cells Support Virus Replication in Sooty Mangabeys Naturally Infected with Simian Immunodeficiency Virus: Implications for AIDS Pathogenesis▿

PubMed Central

Gordon, Shari N.; Dunham, Richard M.; Engram, Jessica C.; Estes, Jacob; Wang, Zichun; Klatt, Nichole R.; Paiardini, Mirko; Pandrea, Ivona V.; Apetrei, Cristian; Sodora, Donald L.; Lee, Ha Youn; Haase, Ashley T.; Miller, Michael D.; Kaur, Amitinder; Staprans, Silvija I.; Perelson, Alan S.; Feinberg, Mark B.; Silvestri, Guido

2008-01-01

Sooty mangabeys (SMs) naturally infected with simian immunodeficiency virus (SIV) do not develop AIDS despite high levels of virus replication. At present, the mechanisms underlying this disease resistance are poorly understood. Here we tested the hypothesis that SIV-infected SMs avoid immunodeficiency as a result of virus replication occurring in infected cells that live significantly longer than human immunodeficiency virus (HIV)-infected human cells. To this end, we treated six SIV-infected SMs with potent antiretroviral therapy (ART) and longitudinally measured the decline in plasma viremia. We applied the same mathematical models used in HIV-infected individuals and observed that SMs naturally infected with SIV also present a two-phase decay of viremia following ART, with the bulk (92 to 99%) of virus replication sustained by short-lived cells (average life span, 1.06 days), and only 1 to 8% occurring in longer-lived cells. In addition, we observed that ART had a limited impact on CD4+ T cells and the prevailing level of T-cell activation and proliferation in SIV-infected SMs. Collectively, these results suggest that in SIV-infected SMs, similar to HIV type 1-infected humans, short-lived activated CD4+ T cells, rather than macrophages, are the main source of virus production. These findings indicate that a short in vivo life span of infected cells is a common feature of both pathogenic and nonpathogenic primate lentivirus infections and support a model for AIDS pathogenesis whereby the direct killing of infected cells by HIV is not the main determinant of disease progression. PMID:18216113

Acetyl-coenzyme A synthetase 2 is a nuclear protein required for replicative longevity in Saccharomyces cerevisiae

PubMed Central

Falcón, Alaric A.; Chen, Shaoping; Wood, Michael S.

2013-01-01

Acs2p is one of two acetyl-coenzyme A synthetases in Saccharomyces cerevisiae. We have prepared and characterized a monoclonal antibody specific for Acs2p and find that Acs2p is localized primarily to the nucleus, including the nucleolus, with a minor amount in the cytosol. We find that Acs2p is required for replicative longevity: an acs2Δ strain has a reduced replicative life span compared to wild-type and acs1Δ strains. Furthermore, replicatively aged acs2Δ cells contain elevated levels of extrachromosomal rDNA circles, and silencing at the rDNA locus is impaired in an acs2Δ strain. These findings indicate that Acs2p-mediated synthesis of acetyl-CoA in the nucleus functions to promote rDNA silencing and replicative longevity in yeast. PMID:19618123

nfi-1 affects behavior and life-span in C. elegans but is not essential for DNA replication or survival

PubMed Central

Lazakovitch, Elena; Kalb, John M; Matsumoto, Reiko; Hirono, Keiko; Kohara, Yuji; Gronostajski, Richard M

2005-01-01

Background The Nuclear Factor I (one) (NFI) family of transcription/replication factors plays essential roles in mammalian gene expression and development and in adenovirus DNA replication. Because of its role in viral DNA replication NFI has long been suspected to function in host DNA synthesis. Determining the requirement for NFI proteins in mammalian DNA replication is complicated by the presence of 4 NFI genes in mice and humans. Loss of individual NFI genes in mice cause defects in brain, lung and tooth development, but the presence of 4 homologous NFI genes raises the issue of redundant roles for NFI genes in DNA replication. No NFI genes are present in bacteria, fungi or plants. However single NFI genes are present in several simple animals including Drosophila and C. elegans, making it possible to test for a requirement for NFI in multicellular eukaryotic DNA replication and development. Here we assess the functions of the single nfi-1 gene in C. elegans. Results C. elegans NFI protein (CeNFI) binds specifically to the same NFI-binding site recognized by vertebrate NFIs. nfi-1 encodes alternatively-spliced, maternally-inherited transcripts that are expressed at the single cell stage, during embryogenesis, and in adult muscles, neurons and gut cells. Worms lacking nfi-1 survive but have defects in movement, pharyngeal pumping and egg-laying and have a reduced life-span. Expression of the muscle gene Ce titin is decreased in nfi-1 mutant worms. Conclusion NFI gene function is not needed for survival in C. elegans and thus NFI is likely not essential for DNA replication in multi-cellular eukaryotes. The multiple defects in motility, egg-laying, pharyngeal pumping, and reduced lifespan indicate that NFI is important for these processes. Reduction in Ce titin expression could affect muscle function in multiple tissues. The phenotype of nfi-1 null worms indicates that NFI functions in multiple developmental and behavioral systems in C. elegans, likely regulating genes that function in motility, egg-laying, pharyngeal pumping and lifespan maintenance. PMID:16242019

The activity-dependent histone variant H2BE modulates the life span of olfactory neurons

PubMed Central

Santoro, Stephen W; Dulac, Catherine

2012-01-01

We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment. DOI: http://dx.doi.org/10.7554/eLife.00070.001 PMID:23240083

The evolutionary ecology of molecular replicators

PubMed Central

2016-01-01

By reasonable criteria, life on the Earth consists mainly of molecular replicators. These include viruses, transposons, transpovirons, coviruses and many more, with continuous new discoveries like Sputnik Virophage. Their study is inherently multidisciplinary, spanning microbiology, genetics, immunology and evolutionary theory, and the current view is that taking a unified approach has great power and promise. We support this with a new, unified, model of their evolutionary ecology, using contemporary evolutionary theory coupling the Price equation with game theory, studying the consequences of the molecular replicators' promiscuous use of each others' gene products for their natural history and evolutionary ecology. Even at this simple expository level, we can make a firm prediction of a new class of replicators exploiting viruses such as lentiviruses like SIVs, a family which includes HIV: these have been explicitly stated in the primary literature to be non-existent. Closely connected to this departure is the view that multicellular organism immunology is more about the management of chronic infections rather than the elimination of acute ones and new understandings emerging are changing our view of the kind of theatre we ourselves provide for the evolutionary play of molecular replicators. This study adds molecular replicators to bacteria in the emerging field of sociomicrobiology. PMID:27853598

The evolutionary ecology of molecular replicators.

PubMed

Nee, Sean

2016-08-01

By reasonable criteria, life on the Earth consists mainly of molecular replicators. These include viruses, transposons, transpovirons, coviruses and many more, with continuous new discoveries like Sputnik Virophage. Their study is inherently multidisciplinary, spanning microbiology, genetics, immunology and evolutionary theory, and the current view is that taking a unified approach has great power and promise. We support this with a new, unified, model of their evolutionary ecology, using contemporary evolutionary theory coupling the Price equation with game theory, studying the consequences of the molecular replicators' promiscuous use of each others' gene products for their natural history and evolutionary ecology. Even at this simple expository level, we can make a firm prediction of a new class of replicators exploiting viruses such as lentiviruses like SIVs, a family which includes HIV: these have been explicitly stated in the primary literature to be non-existent. Closely connected to this departure is the view that multicellular organism immunology is more about the management of chronic infections rather than the elimination of acute ones and new understandings emerging are changing our view of the kind of theatre we ourselves provide for the evolutionary play of molecular replicators. This study adds molecular replicators to bacteria in the emerging field of sociomicrobiology.

Balloon-type versus non-balloon-type replacement percutaneous endoscopic gastrostomy: which is better?

PubMed

Heiser, M; Malaty, H

2001-01-01

Percutaneous endoscopic gastrostomy (PEG) has been an established procedure for nearly 20 years. Caring for patients with a PEG has been incorporated into the practice of nurses in most gastroenterology settings. Several practice-related questions have arisen, particularly in relation to replacement PEGs. In an attempt to obtain relevant information for decisions relating to cost-effectiveness and providing optimum care for PEG replacement, two clinical research questions were studied: (1) is there a difference in patient (stomal) response related to two different replacement PEG tubes, and (2) is there a difference in the duration (life-span) between the two types of replacement tubes? A non-experimental, two-group descriptive study was conducted to answer the two clinical research questions. Two types of replacement PEG tubes were evaluated: a balloon type and a non-balloon type. Stoma response (recording skin and insertion site characteristics) and PEG life span were the measures of interest. Differences in the occurrence of skin and insertion site problems between the two groups were not statistically significant. Differences between the life spans of the two tubes were found to be statistically significant at three time intervals. Findings give information to the practitioner involved in making independent and interdependent practice decisions when planning care for patients with a PEG. Suggestions for additional research and replication are included.

Reaction time inconsistency in a spatial stroop task: age-related differences through childhood and adulthood.

PubMed

Williams, Benjamin R; Strauss, Esther H; Hultsch, David F; Hunter, Michael A

2007-07-01

Age-related differences in inconsistency of reaction time (RT) across the life span were examined on a task with differing levels of demand on executive control. A total of 546 participants, aged 5 to 76 years, completed a spatial Stroop task that permitted observations under three conditions (congruent, incongruent, and neutral) according to the correspondence between the required response (based on stimulus direction) and stimulus location. An interference effect was observed across all ages. Analyses of neutral condition data replicated previous research demonstrating RT inconsistency follows a U-shaped developmental curve across the life span. The relationship between age and inconsistency, however, depended on condition: inconsistency in the congruent condition was higher than inconsistency in both the neutral and incongruent conditions across middle-aged groups. Reaction time inconsistency may reflect processing efficiency that is maximal in young adulthood and may also be sensitive to fluctuations in performance that reflect momentarily highly efficient responding.

Strand-Specific Analysis of DNA Synthesis and Proteins Association with DNA Replication Forks in Budding Yeast.

PubMed

Yu, Chuanhe; Gan, Haiyun; Zhang, Zhiguo

2018-01-01

DNA replication initiates at DNA replication origins after unwinding of double-strand DNA(dsDNA) by replicative helicase to generate single-stranded DNA (ssDNA) templates for the continuous synthesis of leading-strand and the discontinuous synthesis of lagging-strand. Therefore, methods capable of detecting strand-specific information will likely yield insight into the association of proteins at leading and lagging strand of DNA replication forks and the regulation of leading and lagging strand synthesis during DNA replication. The enrichment and Sequencing of Protein-Associated Nascent DNA (eSPAN), which measure the relative amounts of proteins at nascent leading and lagging strands of DNA replication forks, is a step-wise procedure involving the chromatin immunoprecipitation (ChIP) of a protein of interest followed by the enrichment of protein-associated nascent DNA through BrdU immunoprecipitation. The isolated ssDNA is then subjected to strand-specific sequencing. This method can detect whether a protein is enriched at leading or lagging strand of DNA replication forks. In addition to eSPAN, two other strand-specific methods, (ChIP-ssSeq), which detects potential protein-ssDNA binding and BrdU-IP-ssSeq, which can measure synthesis of both leading and lagging strand, were developed along the way. These methods can provide strand-specific and complementary information about the association of the target protein with DNA replication forks as well as synthesis of leading and lagging strands genome wide. Below, we describe the detailed eSPAN, ChIP-ssSeq, and BrdU-IP-ssSeq protocols.

Partial uncoupling of oxidative phosphorylation induces premature senescence in human fibroblasts and yeast mother cells.

PubMed

Stöckl, Petra; Zankl, Christina; Hütter, Eveline; Unterluggauer, Hermann; Laun, Peter; Heeren, Gino; Bogengruber, Edith; Herndler-Brandstetter, Dietmar; Breitenbach, Michael; Jansen-Dürr, Pidder

2007-09-15

The mitochondrial theory of aging predicts that functional alterations in mitochondria leading to reactive oxygen species (ROS) production contribute to the aging process in most if not all species. Using cellular senescence as a model for human aging, we have recently reported partial uncoupling of the respiratory chain in senescent human fibroblasts. In the present communication, we address a potential cause-effect relationship between impaired mitochondrial coupling and premature senescence. Chronic exposure of human fibroblasts to the chemical uncoupler carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) led to a temporary, reversible uncoupling of oxidative phosphorylation. FCCP inhibited cell proliferation in a dose-dependent manner, and a significant proportion of the cells entered premature senescence within 12 days. Unexpectedly, chronic exposure of cells to FCCP led to a significant increase in ROS production, and the inhibitory effect of FCCP on cell proliferation was eliminated by the antioxidant N-acetyl-cysteine. However, antioxidant treatment did not prevent premature senescence, suggesting that a reduction in the level of oxidative phosphorylation contributes to phenotypical changes characteristic of senescent human fibroblasts. To assess whether this mechanism might be conserved in evolution, the influence of mitochondrial uncoupling on replicative life span of yeast cells was also addressed. Similar to our findings in human fibroblasts, partial uncoupling of oxidative phsophorylation in yeast cells led to a substantial decrease in the mother-cell-specific life span and a concomitant incrase in ROS, indicating that life span shortening by mild mitochondrial uncoupling may represent a "public" mechanism of aging.

Long-term effects of intragastic instillations of BDNPF:BDNPA in male Sprague-Dawley rats and female Swiss-Webster mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, D.M.; Drake, G.A.; London, J.E.

1981-07-01

Young male Sprague-Dawley rats were given a single dose of 1.3 g/kg body weight (BW) bis-dinitro-propyl-formal:bisdinitro-propyl-acetal (BDNPF:BDNPA) intragastrically (IG) and young female Swiss-Webster mice were given BDNPF:BDNPA either as a single dose (800 mg/kg/Bw) IG or a dose (500 mg/kg/BW) IG on each of 5 consecutive days. All animals were then maintained for the durations of their life spans and autopsied at death. The incidence of testicular Leydig cell tumors and subcutaneous fibrosarcomas in rats receiving the material was significantly elevated compared to controls, though treated animals' life spans were not significantly different from those of control animals. No significantmore » effects were seen in any of the mice receiving either a single dose or multiple doses of BDNPF:BDNPA compared to control animals. We suggest that another species of male Laboratory animals be treated with BDNPF:BDNPA to see if these findings can be replicated.« less

Effects of shortened host life span on the evolution of parasite life history and virulence in a microbial host-parasite system

PubMed Central

Nidelet, Thibault; Koella, Jacob C; Kaltz, Oliver

2009-01-01

Background Ecological factors play an important role in the evolution of parasite exploitation strategies. A common prediction is that, as shorter host life span reduces future opportunities of transmission, parasites compensate with an evolutionary shift towards earlier transmission. They may grow more rapidly within the host, have a shorter latency time and, consequently, be more virulent. Thus, increased extrinsic (i.e., not caused by the parasite) host mortality leads to the evolution of more virulent parasites. To test these predictions, we performed a serial transfer experiment, using the protozoan Paramecium caudatum and its bacterial parasite Holospora undulata. We simulated variation in host life span by killing hosts after 11 (early killing) or 14 (late killing) days post inoculation; after killing, parasite transmission stages were collected and used for a new infection cycle. Results After 13 cycles (≈ 300 generations), parasites from the early-killing treatment were less infectious, but had shorter latency time and higher virulence than those from the late-killing treatment. Overall, shorter latency time was associated with higher parasite loads and thus presumably with more rapid within-host replication. Conclusion The analysis of the means of the two treatments is thus consistent with theory, and suggests that evolution is constrained by trade-offs between virulence, transmission and within-host growth. In contrast, we found little evidence for such trade-offs across parasite selection lines within treatments; thus, to some extent, these traits may evolve independently. This study illustrates how environmental variation (experienced by the host) can lead to the evolution of distinct parasite strategies. PMID:19320981

Mice Producing Reduced Levels of Insulin-Like Growth Factor Type 1 Display an Increase in Maximum, but not Mean, Life Span

PubMed Central

2014-01-01

Reduced signaling through the IGF type 1 (IGF-1) receptor increases life span in multiple invertebrate organisms. Studies on mammalian longevity suggest that reducing levels of IGF-1 may also increase life span. However, the data are conflicting and complicated by the physiology of the mammalian neuroendocrine system. We have performed life-span analysis on mice homozygous for an insertion in the Igf1 gene. These mice produce reduced levels of IGF-1 and display a phenotype consistent with a significant decrease in IGF-1. Life-span analysis was carried out at three independent locations. Although the life-span data varied between sites, the maximum life span of the IGF-1-deficient mice was significantly increased and age-specific mortality rates were reduced in the IGF-1-deficient mice; however, mean life span did not differ except at one site, where mean life span was increased in female IGF-1-deficient animals. Early life mortality was noted in one cohort of IGF-1-deficient mice. The results are consistent with a significant role for IGF-1 in the modulation of life span but contrast with the published life-span data for the hypopituitary Ames and Snell dwarf mice and growth hormone receptor null mice, indicating that a reduction in IGF-1 alone is insufficient to increase both mean and maximal life span in mice. PMID:23873963

Sex differences, sexual selection, and ageing: an experimental evolution approach.

PubMed

Maklakov, Alexei A; Bonduriansky, Russell; Brooks, Robert C

2009-10-01

Life-history (LH) theory predicts that selection will optimize the trade-off between reproduction and somatic maintenance. Reproductive ageing and finite life span are direct consequences of such optimization. Sexual selection and conflict profoundly affect the reproductive strategies of the sexes and thus can play an important role in the evolution of life span and ageing. In theory, sexual selection can favor the evolution of either faster or slower ageing, but the evidence is equivocal. We used a novel selection experiment to investigate the potential of sexual selection to influence the adaptive evolution of age-specific LH traits. We selected replicate populations of the seed beetle Callosobruchus maculatus for age at reproduction ("Young" and "Old") either with or without sexual selection. We found that LH selection resulted in the evolution of age-specific reproduction and mortality but these changes were largely unaffected by sexual selection. Sexual selection depressed net reproductive performance and failed to promote adaptation. Nonetheless, the evolution of several traits differed between males and females. These data challenge the importance of current sexual selection in promoting rapid adaptation to environmental change but support the hypothesis that sex differences in LH-a historical signature of sexual selection-are key in shaping trait responses to novel selection.

A field experiment demonstrating plant life-history evolution and its eco-evolutionary feedback to seed predator populations.

PubMed

Agrawal, Anurag A; Johnson, Marc T J; Hastings, Amy P; Maron, John L

2013-05-01

The extent to which evolutionary change occurs in a predictable manner under field conditions and how evolutionary changes feed back to influence ecological dynamics are fundamental, yet unresolved, questions. To address these issues, we established eight replicate populations of native common evening primrose (Oenothera biennis). Each population was planted with 18 genotypes in identical frequency. By tracking genotype frequencies with microsatellite DNA markers over the subsequent three years (up to three generations, ≈5,000 genotyped plants), we show rapid and consistent evolution of two heritable plant life-history traits (shorter life span and later flowering time). This rapid evolution was only partially the result of differential seed production; genotypic variation in seed germination also contributed to the observed evolutionary response. Since evening primrose genotypes exhibited heritable variation for resistance to insect herbivores, which was related to flowering time, we predicted that evolutionary changes in genotype frequencies would feed back to influence populations of a seed predator moth that specializes on O. biennis. By the conclusion of the experiment, variation in the genotypic composition among our eight replicate field populations was highly predictive of moth abundance. These results demonstrate how rapid evolution in field populations of a native plant can influence ecological interactions.

Bifurcation into functional niches in adaptation.

PubMed

White, Justin S; Adami, Christoph

2004-01-01

One of the central questions in evolutionary biology concerns the dynamics of adaptation and diversification. This issue can be addressed experimentally if replicate populations adapting to identical environments can be investigated in detail. We have studied 501 such replicas using digital organisms adapting to at least two fundamentally different functional niches (survival strategies) present in the same environment: one in which fast replication is the way to live, and another where exploitation of the environment's complexity leads to complex organisms with longer life spans and smaller replication rates. While these two modes of survival are closely analogous to those expected to emerge in so-called r and K selection scenarios respectively, the bifurcation of evolutionary histories according to these functional niches occurs in identical environments, under identical selective pressures. We find that the branching occurs early, and leads to drastic phenotypic differences (in fitness, sequence length, and gestation time) that are permanent and irreversible. This study confirms an earlier experimental effort using microorganisms, in that diversification can be understood at least in part in terms of bifurcations on saddle points leading to peak shifts, as in the picture drawn by Sewall Wright.

Life-Span Learning: A Developmental Perspective

ERIC Educational Resources Information Center

Thornton, James E.

2003-01-01

The article discusses learning as embedded processes of development and aging, and as social activity over the life course. The concept of life-span learning is proposed and outlined to discuss these processes as aspects of and propositions in life-span development and aging theory. Life-span learning processes arise and continuously develop in a…

Life-Span Extension by Caloric Restriction Is Determined by Type and Level of Food Reduction and by Reproductive Mode in Brachionus manjavacas (Rotifera)

PubMed Central

2013-01-01

We measured life span and fecundity of three reproductive modes in a clone of the monogonont rotifer Brachionus manjavacas subjected to chronic caloric restriction (CCR) over a range of food concentrations or to intermittent fasting (IF). IF increased life span 50%–70% for all three modes, whereas CCR increased life span of asexual females derived from sexually or asexually produced eggs, but not that of sexual females. The main effect of CR on both asexual modes was to delay death at young ages, rather than to prevent death at middle ages or to greatly extend maximum life span; in contrast CR in sexual females greatly increased the life span of a few long-lived individuals. Lifetime fecundity did not decrease with CCR, suggesting a lack of resource allocation trade-off between somatic maintenance and reproduction. Multiple outcomes for a clonal lineage indicate that different responses are established through epigenetic programming, whereas differences in life-span allocations suggest that multiple genetic mechanisms mediate life-span extension. PMID:22904096

Life-span extension by caloric restriction is determined by type and level of food reduction and by reproductive mode in Brachionus manjavacas (Rotifera).

PubMed

Gribble, Kristin E; Welch, David B Mark

2013-04-01

We measured life span and fecundity of three reproductive modes in a clone of the monogonont rotifer Brachionus manjavacas subjected to chronic caloric restriction (CCR) over a range of food concentrations or to intermittent fasting (IF). IF increased life span 50%-70% for all three modes, whereas CCR increased life span of asexual females derived from sexually or asexually produced eggs, but not that of sexual females. The main effect of CR on both asexual modes was to delay death at young ages, rather than to prevent death at middle ages or to greatly extend maximum life span; in contrast CR in sexual females greatly increased the life span of a few long-lived individuals. Lifetime fecundity did not decrease with CCR, suggesting a lack of resource allocation trade-off between somatic maintenance and reproduction. Multiple outcomes for a clonal lineage indicate that different responses are established through epigenetic programming, whereas differences in life-span allocations suggest that multiple genetic mechanisms mediate life-span extension.

Genetic moderation of stability in attachment security from early childhood to age 18 years: A replication study.

PubMed

Raby, K Lee; Roisman, Glenn I; Booth-LaForce, Cathryn

2015-11-01

A longstanding question for attachment theory and research is whether genetically based characteristics of the child influence the development of attachment security and its stability over time. This study attempted to replicate and extend recent findings indicating that the developmental stability of attachment security is moderated by oxytocin receptor (OXTR) genetic variants. Using longitudinal data from over 550 individuals, there was no evidence that OXTR rs53576 moderated the association between attachment security during early childhood and overall coherence of mind ("security") during the Adult Attachment Interview at age 18 years. Additional analyses involving a second commonly investigated OXTR variant (rs2254298) and indices of individuals' dismissing and preoccupied attachment states of mind also failed to provide robust evidence for oxytonergic moderation of the stability in attachment security across development. The discussion focuses on research strategies for investigating genetic contributions to attachment security across the life span. (c) 2015 APA, all rights reserved).

Evolutionary Models for Simple Biosystems

NASA Astrophysics Data System (ADS)

Bagnoli, Franco

The concept of evolutionary development of structures constituted a real revolution in biology: it was possible to understand how the very complex structures of life can arise in an out-of-equilibrium system. The investigation of such systems has shown that indeed, systems under a flux of energy or matter can self-organize into complex patterns, think for instance to Rayleigh-Bernard convection, Liesegang rings, patterns formed by granular systems under shear. Following this line, one could characterize life as a state of matter, characterized by the slow, continuous process that we call evolution. In this paper we try to identify the organizational level of life, that spans several orders of magnitude from the elementary constituents to whole ecosystems. Although similar structures can be found in other contexts like ideas (memes) in neural systems and self-replicating elements (computer viruses, worms, etc.) in computer systems, we shall concentrate on biological evolutionary structure, and try to put into evidence the role and the emergence of network structure in such systems.

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

PubMed

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

2016-04-26

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

Mixed emotions across the adult life span in the United States

PubMed Central

Schneider, Stefan; Stone, Arthur A.

2015-01-01

Mixed emotions involve the co-occurrence of positive and negative affect, such that people feel happy and sad at the same time. The purpose of the present study was to investigate age-related differences in the experience of mixed emotions across the adult life span in two nationally representative samples of U.S. residents. Data collected by the Princeton Affect and Time Survey (PATS, n = 3,948) and by the 2010 Wellbeing Module of the American Time Use Survey (ATUS, n = 12,828) were analyzed. In both surveys, respondents (aged 15 years or older) provided a detailed time diary about the preceding day and rated their happiness and sadness for three of the day's episodes. From these reports, three different indices of mixed emotions were derived. Results indicated small, but robust, increases in mixed emotions with age. Linear age increases were consistently evident in both PATS and ATUS, and replicated across the different indices of mixed emotions. There was no significant evidence for curvilinear age trends in either study. Several sociodemographic factors that could plausibly explain age-differences in mixed emotions (e.g., retirement, disability) did not alter the age-effects. The present study adds to the growing literature documenting vital changes in the complexity of emotional experience over the lifespan. PMID:25894487

Comparative transcriptional profiling identifies takeout as a gene that regulates life span

PubMed Central

Bauer, Johannes; Antosh, Michael; Chang, Chengyi; Schorl, Christoph; Kolli, Santharam; Neretti, Nicola; Helfand, Stephen L.

2010-01-01

A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular genetic life span extending interventions related to DR, increased dSir2 and decreased Dmp53 activity. We find twenty-one genes shared among the three related life span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah. We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway. PMID:20519778

Replicative age induces mitotic recombination in the ribosomal RNA gene cluster of Saccharomyces cerevisiae.

PubMed

Lindstrom, Derek L; Leverich, Christina K; Henderson, Kiersten A; Gottschling, Daniel E

2011-03-01

Somatic mutations contribute to the development of age-associated disease. In earlier work, we found that, at high frequency, aging Saccharomyces cerevisiae diploid cells produce daughters without mitochondrial DNA, leading to loss of respiration competence and increased loss of heterozygosity (LOH) in the nuclear genome. Here we used the recently developed Mother Enrichment Program to ask whether aging cells that maintain the ability to produce respiration-competent daughters also experience increased genomic instability. We discovered that this population exhibits a distinct genomic instability phenotype that primarily affects the repeated ribosomal RNA gene array (rDNA array). As diploid cells passed their median replicative life span, recombination rates between rDNA arrays on homologous chromosomes progressively increased, resulting in mutational events that generated LOH at >300 contiguous open reading frames on the right arm of chromosome XII. We show that, while these recombination events were dependent on the replication fork block protein Fob1, the aging process that underlies this phenotype is Fob1-independent. Furthermore, we provide evidence that this aging process is not driven by mechanisms that modulate rDNA recombination in young cells, including loss of cohesion within the rDNA array or loss of Sir2 function. Instead, we suggest that the age-associated increase in rDNA recombination is a response to increasing DNA replication stress generated in aging cells.

Verification of immune response optimality through cybernetic modeling.

PubMed

Batt, B C; Kompala, D S

1990-02-09

An immune response cascade that is T cell independent begins with the stimulation of virgin lymphocytes by antigen to differentiate into large lymphocytes. These immune cells can either replicate themselves or differentiate into plasma cells or memory cells. Plasma cells produce antibody at a specific rate up to two orders of magnitude greater than large lymphocytes. However, plasma cells have short life-spans and cannot replicate. Memory cells produce only surface antibody, but in the event of a subsequent infection by the same antigen, memory cells revert rapidly to large lymphocytes. Immunologic memory is maintained throughout the organism's lifetime. Many immunologists believe that the optimal response strategy calls for large lymphocytes to replicate first, then differentiate into plasma cells and when the antigen has been nearly eliminated, they form memory cells. A mathematical model incorporating the concept of cybernetics has been developed to study the optimality of the immune response. Derived from the matching law of microeconomics, cybernetic variables control the allocation of large lymphocytes to maximize the instantaneous antibody production rate at any time during the response in order to most efficiently inactivate the antigen. A mouse is selected as the model organism and bacteria as the replicating antigen. In addition to verifying the optimal switching strategy, results showing how the immune response is affected by antigen growth rate, initial antigen concentration, and the number of antibodies required to eliminate an antigen are included.

Ancestral telomere shortening: a countdown that will increase mean life span?

PubMed

Hertzog, Radu G

2006-01-01

Like cells, all mammals have a limited life span. Among cells there are a few exceptions (e.g., immortal cells), among mammals not, even if some of them live longer. Many in vitro and in vivo studies support the consensus that telomere length is strongly correlated with life span. At the somatic cellular level, long telomeres have been associated with longer life span. A different situation can be seen in immortal cells, such as cancer, germ and stem cells, where telomeres are maintained by telomerase, a specialized reverse transcriptase that is involved in synthesis of telomeres. Irrespective of telomere length, if telomerase is active, telomeres can be maintained at a sufficient length to ensure cell survival. To the contrary, telomeres shorten progressively with each cell division and when a critical telomere length (Hayflick limit) is reached, the cells undergo senescence and subsequently apoptosis. In mammals, those with the longest telomeres (e.g., mice) have the shortest life span. Furthermore, the shorter the mean telomere length, the longer the mean life span, as observed in humans (10-14 kpb) and bowhead-whales (undetermined telomere length), which have the longest mean life span among mammals. Over the past centuries, human average life span has increased. The hypothesis presented here suggests that this continual increase in the mean life span could be due to a decrease of mean telomere length over the last hundreds years. Actually, the life span is not directly influenced by length of telomeres, but rather by telomere length - dependent gene expression pattern. According to Greider, "rather than average telomere length, it is the shortest telomere length that makes the biggest difference to a cell". In the context of fast-growing global elderly population due to increase in life expectancy, it also seem to be an age related increase in cancer incidence. Nevertheless, extending healthy life span could depend on how good cells achieve, during the prenatal period and few years after birth, the equilibrium between telomere length and telomerase activity, as seen in germ cells. After all, I suggest that decrease in mean telomere length might result in, on the one hand, an increased life span and, on the other, a higher risk of tumorigenesis.

The meaning of death: some simulations of a model of healthy and unhealthy consumption.

PubMed

Forster, M

2001-07-01

Simulations of a model of healthy and unhealthy consumption are used to investigate the impact of various terminal conditions on life-span, pathways of health-related consumption and health. A model in which life-span and the 'death' stock of health are fixed is compared to versions in which (i) the 'death' stock of health is freely chosen; (ii) life-span is freely chosen; (iii) both the 'death' stock of health and life-span are freely chosen. The choice of terminal conditions has a striking impact on optimal plans. Results are discussed with reference to the existing demand for health literature and illustrate the application of iterative processes to determine optimal life-span, the role played by the marginal value of health capital in determining optimal plans, and the importance of checking the second-order conditions for the optimal choice of life-span.

Bringing history to life: simulating landmark experiments in psychology.

PubMed

Boynton, David M; Smith, Laurence D

2006-05-01

The course in history of psychology can be challenging for students, many of whom enter it with little background in history and faced with unfamiliar names and concepts. The sheer volume of material can encourage passive memorization unless efforts are made to increase student involvement. As part of a trend toward experiential history, historians of science have begun to supplement their lectures with demonstrations of classic physics experiments as a way to bring the history of science to life. Here, the authors report on computer simulations of five landmark experiments from early experimental psychology in the areas of reaction time, span of attention, and apparent motion. The simulations are designed not only to permit hands-on replication of historically important results but also to reproduce the experimental procedures closely enough that students can gain a feel for the nature of early research and the psychological processes being studied.

Magical thinking decreases across adulthood.

PubMed

Brashier, Nadia M; Multhaup, Kristi S

2017-12-01

Magical thinking, or illogical causal reasoning such as superstitions, decreases across childhood, but almost no data speak to whether this developmental trajectory continues across the life span. In four experiments, magical thinking decreased across adulthood. This pattern replicated across two judgment domains and could not be explained by age-related differences in tolerance of ambiguity, domain-specific knowledge, or search for meaning. These data complement and extend findings that experience, accumulated over decades, guides older adults' judgments so that they match, or even exceed, young adults' performance. They also counter participants' expectations, and cultural sayings (e.g., "old wives' tales"), that suggest that older adults are especially superstitious. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Causation and the origin of life. Metabolism or replication first?

PubMed

Pross, Addy

2004-06-01

The conceptual gulf that separates the 'metabolism first' and 'replication first' mechanisms for the emergence of life continues to cloud the origin of life debate. In the present paper we analyze this aspect of the origin of life problem and offer arguments in favor of the 'replication first' school. Utilizing Wicken's two-tier approach to causation we argue that a causal connection between replication and metabolism can only be demonstrated if replication would have preceded metabolism. In conjunction with existing empirical evidence and theoretical reasoning, our analysis concludes that there is no substantive evidence for a 'metabolism first' mechanism for life's emergence, while a coherent case can be made for the 'replication first' group of mechanisms. The analysis reaffirms our conviction that life is an extreme expression of kinetic control, and that the emergence of metabolic pathways can be understood by considering life as a manifestation of 'replicative chemistry'.

A Motivational Theory of Life-Span Development

PubMed Central

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 action-phase model of developmental regulation with their original life-span theory of control to present a comprehensive theory of development. Third, they reviewed the relevant empirical literature testing key propositions of the Motivational Theory of Life-Span Development. Finally, because the conceptual reach of their theory goes far beyond the current empirical base, they pointed out areas that deserve further and more focused empirical inquiry. PMID:20063963

Longevity and age-related lesions in a laboratory colony of grasshopper mice, Onychomys leucogaster

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Farrell, T.P.; Cosgrove, G.E.

1975-07-01

Mated pairs of northern grasshopper mice, Onychomys leucogaster fuscogriseus, were maintained in a laboratory colony to determine their median longevity, maximum life span, and age-related pathologies. Median life span for both sexes and four cohorts was 1411 days and the maximum life span was 1915 days. There were no significant differences between sexes, but cohorts 5-7 generations removed from wild-caught parents had shorter median life spans. (auth)

Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus

PubMed Central

Bergström, Tomas; Kann, Nina; Adamiak, Beata; Hannoun, Charles; Kindler, Eveline; Jónsdóttir, Hulda R.; Muth, Doreen; Kint, Joeri; Forlenza, Maria; Müller, Marcel A.; Drosten, Christian; Thiel, Volker; Trybala, Edward

2014-01-01

Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS–CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections. PMID:24874215

How long will my mouse live? Machine learning approaches for prediction of mouse life span.

PubMed

Swindell, William R; Harper, James M; Miller, Richard A

2008-09-01

Prediction of individual life span based on characteristics evaluated at middle-age represents a challenging objective for aging research. In this study, we used machine learning algorithms to construct models that predict life span in a stock of genetically heterogeneous mice. Life-span prediction accuracy of 22 algorithms was evaluated using a cross-validation approach, in which models were trained and tested with distinct subsets of data. Using a combination of body weight and T-cell subset measures evaluated before 2 years of age, we show that the life-span quartile to which an individual mouse belongs can be predicted with an accuracy of 35.3% (+/-0.10%). This result provides a new benchmark for the development of life-span-predictive models, but improvement can be expected through identification of new predictor variables and development of computational approaches. Future work in this direction can provide tools for aging research and will shed light on associations between phenotypic traits and longevity.

Human Keratinocytes That Express hTERT and Also Bypass a p16INK4a-Enforced Mechanism That Limits Life Span Become Immortal yet Retain Normal Growth and Differentiation Characteristics

PubMed Central

Dickson, Mark A.; Hahn, William C.; Ino, Yasushi; Ronfard, Vincent; Wu, Jenny Y.; Weinberg, Robert A.; Louis, David N.; Li, Frederick P.; Rheinwald, James G.

2000-01-01

Normal human cells exhibit a limited replicative life span in culture, eventually arresting growth by a process termed senescence. Progressive telomere shortening appears to trigger senescence in normal human fibroblasts and retinal pigment epithelial cells, as ectopic expression of the telomerase catalytic subunit, hTERT, immortalizes these cell types directly. Telomerase expression alone is insufficient to enable certain other cell types to evade senescence, however. Such cells, including keratinocytes and mammary epithelial cells, appear to require loss of the pRB/p16INK4a cell cycle control mechanism in addition to hTERT expression to achieve immortality. To investigate the relationships among telomerase activity, cell cycle control, senescence, and differentiation, we expressed hTERT in two epithelial cell types, keratinocytes and mesothelial cells, and determined the effect on proliferation potential and on the function of cell-type-specific growth control and differentiation systems. Ectopic hTERT expression immortalized normal mesothelial cells and a premalignant, p16INK4a-negative keratinocyte line. In contrast, when four keratinocyte strains cultured from normal tissue were transduced to express hTERT, they were incompletely rescued from senescence. After reaching the population doubling limit of their parent cell strains, hTERT+ keratinocytes entered a slow growth phase of indefinite length, from which rare, rapidly dividing immortal cells emerged. These immortal cell lines frequently had sustained deletions of the CDK2NA/INK4A locus or otherwise were deficient in p16INK4a expression. They nevertheless typically retained other keratinocyte growth controls and differentiated normally in culture and in xenografts. Thus, keratinocyte replicative potential is limited by a p16INK4a-dependent mechanism, the activation of which can occur independent of telomere length. Abrogation of this mechanism together with telomerase expression immortalizes keratinocytes without affecting other major growth control or differentiation systems. PMID:10648628

Exploratory and problem-solving consumer behavior across the life span.

PubMed

Lesser, J A; Kunkel, S R

1991-09-01

Different cognitive functioning, social, and personality changes appear to occur systematically during the adult life span. This article synthesizes research on life span changes in order to develop age-specific models of shopping behavior. The models are tested within a naturalistic field study of shoppers.

Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring

PubMed Central

Gribble, Kristin E; Jarvis, George; Bock, Martha; Mark Welch, David B

2014-01-01

While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve health span and life span. PMID:24661622

The Relationship between Speech Rate and Memory Span in Children.

ERIC Educational Resources Information Center

Henry, Lucy A.

1994-01-01

Examined whether speech rate is related to the amount recalled and if developmental increases in speech rate allow faster rehearsal with age, and hence, greater recall. Found that the group relationship was clear and replicable but that speech rates of individual children were not good predictors of those children's memory spans; age was found to…

Relation of Three Mechanisms of Working Memory to Children's Complex Span Performance

ERIC Educational Resources Information Center

Magimairaj, Beula; Montgomery, James; Marinellie, Sally; McCarthy, John

2009-01-01

There is a paucity of research examining the relative contribution of the different mechanisms of working memory (short-term storage [STM], processing speed) to children's complex memory span. This study served to replicate and extend the few extant studies that have examined the issue. In this study, the relative contribution of three mechanisms…

On the Nature of Forgetting and the Processing--Storage Relationship in Reading Span Performance

ERIC Educational Resources Information Center

Saito, Satoru; Miyake, Akira

2004-01-01

Four experiments examined the nature of forgetting and the processing--storage relationship during performance on a prevalent working memory task, the reading span test. Using two different presentation paradigms, Experiments 1 and 2 replicated Towse, Hitch, and Hutton's (1998, 2000) finding that the Short-Final lists, which presented a long…

Developmental Regulation across the Life Span: Toward a New Synthesis

ERIC Educational Resources Information Center

Haase, Claudia M.; Heckhausen, Jutta; Wrosch, Carsten

2013-01-01

How can individuals regulate their own development to live happy, healthy, and productive lives? Major theories of developmental regulation across the life span have been proposed (e.g., dual-process model of assimilation and accommodation; motivational theory of life-span development; model of selection, optimization, and compensation), but they…

A Motivational Theory of Life-Span Development

ERIC Educational Resources Information Center

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…

Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

DOEpatents

Stampfer, Martha R.; Garbe, James C.

2016-06-28

Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

Increasing cell culture population doublings for long-term growth of finite life span human cell cultures

DOEpatents

Stampfer, Martha R; Garbe, James C

2015-02-24

Cell culture media formulations for culturing human epithelial cells are herein described. Also described are methods of increasing population doublings in a cell culture of finite life span human epithelial cells and prolonging the life span of human cell cultures. Using the cell culture media disclosed alone and in combination with addition to the cell culture of a compound associated with anti-stress activity achieves extended growth of pre-stasis cells and increased population doublings and life span in human epithelial cell cultures.

Sexual Conflict, Life Span, and Aging

PubMed Central

Adler, Margo I.; Bonduriansky, Russell

2014-01-01

The potential for sexual conflict to influence the evolution of life span and aging has been recognized for more than a decade, and recent work also suggests that variation in life span and aging can influence sexually antagonistic coevolution. However, empirical exploration of these ideas is only beginning. Here, we provide an overview of the ideas and evidence linking inter- and intralocus sexual conflicts with life span and aging. We aim to clarify the conceptual basis of this research program, examine the current state of knowledge, and suggest key questions for further investigation. PMID:24938876

Lifelong alpha-tocopherol supplementation increases the median life span of C57BL/6 mice in the cold but has only minor effects on oxidative damage.

PubMed

Selman, Colin; McLaren, Jane S; Mayer, Claus; Duncan, Jackie S; Collins, Andrew R; Duthie, Garry G; Redman, Paula; Speakman, John R

2008-02-01

The effects of dietary antioxidant supplementation on oxidative stress and life span are confused. We maintained C57BL/6 mice at 7 +/- 2 degrees C and supplemented their diet with alpha-tocopherol from 4 months of age. Supplementation significantly increased (p = 0.042) median life span by 15% (785 days, n = 44) relative to unsupplemented controls (682 days, n = 43) and also increased maximum life span (oldest 10%, p = 0.028). No sex or sex by treatment interaction effects were observed on life span, with treatment having no effect on resting or daily metabolic rate. Lymphocyte and hepatocyte oxidative DNA damage and hepatic lipid peroxidation were unaffected by supplementation, but hepatic oxidative DNA damage increased with age. Using a cDNA macroarray, genes associated with xenobiotic metabolism were significantly upregulated in the livers of female mice at 6 months of age (2 months supplementation). At 22 months of age (18 months supplementation) this response had largely abated, but various genes linked to the p21 signaling pathway were upregulated at this time. We suggest that alpha-tocopherol may initially be metabolized as a xenobiotic, potentially explaining why previous studies observe a life span extension generally when lifelong supplementation is initiated early in life. The absence of any significant effect on oxidative damage suggests that the life span extension observed was not mediated via any antioxidant properties of alpha-tocopherol. We propose that the life span extension observed following alpha-tocopherol supplementation may be mediated via upregulation of cytochrome p450 genes after 2 months of supplementation and/or upregulation of p21 signaling genes after 18 months of supplementation. However, these signaling pathways now require further investigation to establish their exact role in life span extension following alpha-tocopherol supplementation.

The Emergence of Life as a First-Order Phase Transition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mathis, Cole; Bhattacharya, Tanmoy; Walker, Sara Imari

It is well known that life on Earth alters its environment over evolutionary and geological timescales. An important open question is whether this is a result of evolutionary optimization or a universal feature of life. In the latter case, the origin of life would be coincident with a shift in environmental conditions. Here in this paper we present a model for the emergence of life in which replicators are explicitly coupled to their environment through the recycling of a finite supply of resources. The model exhibits a dynamic, first-order phase transition from nonlife to life, where the life phase ismore » distinguished by selection on replicators. We show that environmental coupling plays an important role in the dynamics of the transition. The transition corresponds to a redistribution of matter in replicators and their environment, driven by selection on replicators, exhibiting an explosive growth in diversity as replicators are selected. The transition is accurately tracked by the mutual information shared between replicators and their environment. In the absence of successfully repartitioning system resources, the transition fails to complete, leading to the possibility of many frustrated trials before life first emerges. Often, the replicators that initiate the transition are not those that are ultimately selected. The results are consistent with the view that life's propensity to shape its environment is indeed a universal feature of replicators, characteristic of the transition from nonlife to life. We discuss the implications of these results for understanding life's emergence and evolutionary transitions more broadly.« less

The Emergence of Life as a First-Order Phase Transition

DOE PAGES

Mathis, Cole; Bhattacharya, Tanmoy; Walker, Sara Imari

2017-03-01

It is well known that life on Earth alters its environment over evolutionary and geological timescales. An important open question is whether this is a result of evolutionary optimization or a universal feature of life. In the latter case, the origin of life would be coincident with a shift in environmental conditions. Here in this paper we present a model for the emergence of life in which replicators are explicitly coupled to their environment through the recycling of a finite supply of resources. The model exhibits a dynamic, first-order phase transition from nonlife to life, where the life phase ismore » distinguished by selection on replicators. We show that environmental coupling plays an important role in the dynamics of the transition. The transition corresponds to a redistribution of matter in replicators and their environment, driven by selection on replicators, exhibiting an explosive growth in diversity as replicators are selected. The transition is accurately tracked by the mutual information shared between replicators and their environment. In the absence of successfully repartitioning system resources, the transition fails to complete, leading to the possibility of many frustrated trials before life first emerges. Often, the replicators that initiate the transition are not those that are ultimately selected. The results are consistent with the view that life's propensity to shape its environment is indeed a universal feature of replicators, characteristic of the transition from nonlife to life. We discuss the implications of these results for understanding life's emergence and evolutionary transitions more broadly.« less

The Emergence of Life as a First-Order Phase Transition

NASA Astrophysics Data System (ADS)

Mathis, Cole; Bhattacharya, Tanmoy; Imari Walker, Sara

2017-03-01

It is well known that life on Earth alters its environment over evolutionary and geological timescales. An important open question is whether this is a result of evolutionary optimization or a universal feature of life. In the latter case, the origin of life would be coincident with a shift in environmental conditions. Here we present a model for the emergence of life in which replicators are explicitly coupled to their environment through the recycling of a finite supply of resources. The model exhibits a dynamic, first-order phase transition from nonlife to life, where the life phase is distinguished by selection on replicators. We show that environmental coupling plays an important role in the dynamics of the transition. The transition corresponds to a redistribution of matter in replicators and their environment, driven by selection on replicators, exhibiting an explosive growth in diversity as replicators are selected. The transition is accurately tracked by the mutual information shared between replicators and their environment. In the absence of successfully repartitioning system resources, the transition fails to complete, leading to the possibility of many frustrated trials before life first emerges. Often, the replicators that initiate the transition are not those that are ultimately selected. The results are consistent with the view that life's propensity to shape its environment is indeed a universal feature of replicators, characteristic of the transition from nonlife to life. We discuss the implications of these results for understanding life's emergence and evolutionary transitions more broadly.

Saccharomyces cerevisiae YOR071C encodes the high affinity nicotinamide riboside transporter Nrt1.

PubMed

Belenky, Peter A; Moga, Tiberiu G; Brenner, Charles

2008-03-28

NAD(+) is an essential coenzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD(+)-consuming enzymes. Nicotinamide riboside is a recently discovered eukaryotic NAD(+) precursor converted to NAD(+) via the nicotinamide riboside kinase pathway and by nucleosidase activity and nicotinamide salvage. Nicotinamide riboside supplementation of yeast extends replicative life span on high glucose medium. The molecular basis for nicotinamide riboside uptake was unknown in any eukaryote. Here, we show that deletion of a single gene, YOR071C, abrogates nicotinamide riboside uptake without altering nicotinic acid or nicotinamide import. The gene, which is negatively regulated by Sum1, Hst1, and Rfm1, fully restores nicotinamide riboside import and utilization when resupplied to mutant yeast cells. The encoded polypeptide, Nrt1, is a predicted deca-spanning membrane protein related to the thiamine transporter, which functions as a pH-dependent facilitator with a K(m) for nicotinamide riboside of 22 microm. Nrt1-related molecules are conserved in particular fungi, suggesting a similar basis for nicotinamide riboside uptake.

The fundamental units, processes and patterns of evolution, and the Tree of Life conundrum

PubMed Central

Koonin, Eugene V; Wolf, Yuri I

2009-01-01

Background The elucidation of the dominant role of horizontal gene transfer (HGT) in the evolution of prokaryotes led to a severe crisis of the Tree of Life (TOL) concept and intense debates on this subject. Concept Prompted by the crisis of the TOL, we attempt to define the primary units and the fundamental patterns and processes of evolution. We posit that replication of the genetic material is the singular fundamental biological process and that replication with an error rate below a certain threshold both enables and necessitates evolution by drift and selection. Starting from this proposition, we outline a general concept of evolution that consists of three major precepts. 1. The primary agency of evolution consists of Fundamental Units of Evolution (FUEs), that is, units of genetic material that possess a substantial degree of evolutionary independence. The FUEs include both bona fide selfish elements such as viruses, viroids, transposons, and plasmids, which encode some of the information required for their own replication, and regular genes that possess quasi-independence owing to their distinct selective value that provides for their transfer between ensembles of FUEs (genomes) and preferential replication along with the rest of the recipient genome. 2. The history of replication of a genetic element without recombination is isomorphously represented by a directed tree graph (an arborescence, in the graph theory language). Recombination within a FUE is common between very closely related sequences where homologous recombination is feasible but becomes negligible for longer evolutionary distances. In contrast, shuffling of FUEs occurs at all evolutionary distances. Thus, a tree is a natural representation of the evolution of an individual FUE on the macro scale, but not of an ensemble of FUEs such as a genome. 3. The history of life is properly represented by the "forest" of evolutionary trees for individual FUEs (Forest of Life, or FOL). Search for trends and patterns in the FOL is a productive direction of study that leads to the delineation of ensembles of FUEs that evolve coherently for a certain time span owing to a shared history of vertical inheritance or horizontal gene transfer; these ensembles are commonly known as genomes, taxa, or clades, depending on the level of analysis. A small set of genes (the universal genetic core of life) might show a (mostly) coherent evolutionary trend that transcends the entire history of cellular life forms. However, it might not be useful to denote this trend "the tree of life", or organismal, or species tree because neither organisms nor species are fundamental units of life. Conclusion A logical analysis of the units and processes of biological evolution suggests that the natural fundamental unit of evolution is a FUE, that is, a genetic element with an independent evolutionary history. Evolution of a FUE on the macro scale is naturally represented by a tree. Only the full compendium of trees for individual FUEs (the FOL) is an adequate depiction of the evolution of life. Coherent evolution of FUEs over extended evolutionary intervals is a crucial aspect of the history of life but a "species" or "organismal" tree is not a fundamental concept. Reviewers This articles was reviewed by Valerian Dolja, W. Ford Doolittle, Nicholas Galtier, and William Martin PMID:19788730

Exploring the dimensionality of digit span.

PubMed

Bowden, Stephen C; Petrauskas, Vilija M; Bardenhagen, Fiona J; Meade, Catherine E; Simpson, Leonie C

2013-04-01

The Digit Span subtest from the Wechsler Scales is used to measure Freedom from Distractibility or Working Memory. Some published research suggests that Digit Span forward should be interpreted differently from Digit Span backward. The present study explored the dimensionality of the Wechsler Memory Scale-III Digit Span (forward and backward) items in a sample of heterogeneous neuroscience patients (n = 267) using confirmatory factor analysis (CFA) for dichotomous items. Results suggested that four correlated factors underlie Digit Span, reflecting easy and hard items in both forward and backward presentation orders. The model for Digit Span was then cross-validated in a seizure disorders sample (n = 223) by replication of the CFA and by examination of measurement invariance. Measurement invariance tests of the precise numerical generalization of trait estimation across groups. Results supported measurement invariance and it was concluded that forward and backward digit span scores should be interpreted as measures of the same cognitive ability.

Blade life span, structural investment, and nutrient allocation in giant kelp.

PubMed

Rodriguez, Gabriel E; Reed, Daniel C; Holbrook, Sally J

2016-10-01

The turnover of plant biomass largely determines the amount of energy flowing through an ecosystem and understanding the processes that regulate turnover has been of interest to ecologists for decades. Leaf life span theory has proven useful in explaining patterns of leaf turnover in relation to resource availability, but the predictions of this theory have not been tested for macroalgae. We measured blade life span, size, thickness, nitrogen content, pigment content, and maximum photosynthetic rate (P max) in the giant kelp (Macrocystis pyrifera) along a strong resource (light) gradient to test whether the predictions of leaf life span theory applied to this alga. We found that shorter blade life spans and larger blade areas were associated with increased light availability. In addition, nitrogen and P max decreased with blade age, and their decrease was greater in shorter lived blades. These observations are generally consistent with patterns observed for higher plants and the prevailing theory of leaf life span. By contrast, variation observed in pigments of giant kelp was inconsistent with that predicted by leaf life span theory, as blades growing in the most heavily shaded portion of the forest had the lowest chlorophyll content. This result may reflect the dual role of macroalgal blades in carbon fixation and nutrient absorption and the ability of giant kelp to modify blade physiology to optimize the acquisition of light and nutrients. Thus, the marine environment may place demands on resource acquisition and allocation that have not been previously considered with respect to leaf life span optimization.

78. VIEW SHOWING PLACEMENT OF LIFE SPAN SHOE ON PIER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

78. VIEW SHOWING PLACEMENT OF LIFE SPAN SHOE ON PIER 6, LOOKING NORTH, March 5, 1935 - Sacramento River Bridge, Spanning Sacramento River at California State Highway 275, Sacramento, Sacramento County, CA

Eyewitness identification across the life span: A meta-analysis of age differences.

PubMed

Fitzgerald, Ryan J; Price, Heather L

2015-11-01

Lineup identifications are often a critical component of criminal investigations. Over the past 35 years, researchers have been conducting empirical studies to assess the impact of witness age on identification accuracy. A previous meta-analysis indicated that children are less likely than adults to correctly reject a lineup that does not contain the culprit, but children 5 years and older are as likely as adults to make a correct identification if the culprit is in the lineup (Pozzulo & Lindsay, 1998). We report an updated meta-analysis of age differences in eyewitness identification, summarizing data from 20,244 participants across 91 studies. Contrary to extant reviews, we adopt a life span approach and examine witnesses from early childhood to late adulthood. Children's increased tendency to erroneously select a culprit-absent lineup member was replicated. Children were also less likely than young adults to correctly identify the culprit. Group data from culprit-absent and culprit-present lineups were used to produce signal detection measures, which indicated young adults were better able than children to discriminate between guilty and innocent suspects. A strikingly similar pattern emerged for older adults, who had even stronger deficits in discriminability than children, relative to adults. Although identifications by young adults were the most reliable, identifications by all witnesses had probative value. (c) 2015 APA, all rights reserved).

Learning From Leaders: Life-span Trends in Olympians and Supercentenarians

PubMed Central

Berthelot, Geoffroy; Marck, Adrien; Noirez, Philippe; Latouche, Aurélien; Toussaint, Jean-François

2015-01-01

Life-span trends progression has worldwide practical implications as it may affect the sustainability of modern societies. We aimed to describe the secular life-span trends of populations with a propensity to live longer—Olympians and supercentenarians—under two hypotheses: an ongoing life-span extension versus a biologic “probabilistic barrier” limiting further progression. In a study of life-span densities (total number of life durations per birth date), we analyzed 19,012 Olympians and 1,205 supercentenarians deceased between 1900 and 2013. Among most Olympians, we observed a trend toward increased life duration. This trend, however, decelerates at advanced ages leveling off with the upper values with a perennial gap between Olympians and supercentenarians during the whole observation period. Similar tendencies are observed among supercentenarians, and over the last years, a plateau attests to a stable longevity pattern among the longest-lived humans. The common trends between Olympians and supercentenarians indicate similar mortality pressures over both populations that increase with age, scenario better explained by a biologic “barrier” forecast. PMID:25143003

Individual differences in memory span: the contribution of rehearsal, access to lexical memory, and output speed.

PubMed

Tehan, G; Lalor, D M

2000-11-01

Rehearsal speed has traditionally been seen to be the prime determinant of individual differences in memory span. Recent studies, in the main using young children as the subject population, have suggested other contributors to span performance, notably contributions from long-term memory and forgetting and retrieval processes occurring during recall. In the current research we explore individual differences in span with respect to measures of rehearsal, output time, and access to lexical memory. We replicate standard short-term phenomena; we show that the variables that influence children's span performance influence adult performance in the same way; and we show that lexical memory access appears to be a more potent source of individual differences in span than either rehearsal speed or output factors.

What Prolongs a Butterfly's Life?: Trade-Offs between Dormancy, Fecundity and Body Size

PubMed Central

Haeler, Elena; Fiedler, Konrad; Grill, Andrea

2014-01-01

In butterflies, life span often increases only at the expense of fecundity. Prolonged life span, on the other hand, provides more opportunities for oviposition. Here, we studied the association between life span and summer dormancy in two closely related species of Palearctic Meadow Brown butterflies, the endemic Maniola nurag and the widespread M. jurtina, from two climatic provenances, a Mediterranean and a Central European site, and tested the relationships between longevity, body size and fecundity. We experimentally induced summer dormancy and hence prolonged the butterflies’ life in order to study the effects of such a prolonged life. We were able to modulate longevity only in Mediterranean females by rearing them under summer photoperiodic conditions (light 16 h : dark 8 h), thereby more than doubling their natural life span, to up to 246 days. Central European individuals kept their natural average live span under all treatments, as did Mediterranean individuals under autumn treatment (light 11: dark 13). Body size only had a significant effect in the smaller species, M. nurag, where it affected the duration of dormancy and lifetime fecundity. In the larger species, M. jurtina, a prolonged adult life span did, surprisingly, not convey any fecundity loss. In M. nurag, which generally deposited fewer eggs, extended life had a fecundity cost. We conclude that Mediterranen M. jurtina butterflies have an extraordinary plasticity in aging which allows them to extend life span in response to adverse environmental conditions and relieve the time limitation on egg-laying while maintaining egg production at equal levels. PMID:25390334

Teaching the Psychology of Aging: A Life-Span Perspective.

ERIC Educational Resources Information Center

Seltzer, Mildred M.

There is a vast body of literature devoted to an examination of life-span development. Several authors have described the characteristics of the life-span approach and have distinguished it from more traditional forms of psychology. Emphasis has been placed on the multidirectional and multidimensional nature of development and change, as well as…

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

ERIC Educational Resources Information Center

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…

SIR2 and other genes are abundantly expressed in long-lived natural segregants for replicative aging of the budding yeast Saccharomyces cerevisiae.

PubMed

Guo, Zhenhua; Adomas, Aleksandra B; Jackson, Erin D; Qin, Hong; Townsend, Jeffrey P

2011-06-01

We investigated the mechanism underlying the natural variation in longevity within natural populations using the model budding yeast, Saccharomyces cerevisiae. We analyzed whole-genome gene expression in four progeny of a natural S. cerevisiae strain that display differential replicative aging. Genes with different expression levels in short- and long-lived strains were classified disproportionately into metabolism, transport, development, transcription or cell cycle, and organelle organization (mitochondrial, chromosomal, and cytoskeletal). With several independent validating experiments, we detected 15 genes with consistent differential expression levels between the long- and the short-lived progeny. Among those 15, SIR2, HSP30, and TIM17 were upregulated in long-lived strains, which is consistent with the known effects of gene silencing, stress response, and mitochondrial function on aging. The link between SIR2 and yeast natural life span variation offers some intriguing ties to the allelic association of the human homolog SIRT1 to visceral obesity and metabolic response to lifestyle intervention. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

High-Dose Nicotinamide Suppresses ROS Generation and Augments Population Expansion during CD8(+) T Cell Activation.

PubMed

Choi, Ho Jin; Jang, So-Young; Hwang, Eun Seong

2015-10-01

During T cell activation, mitochondrial content increases to meet the high energy demand of rapid cell proliferation. With this increase, the level of reactive oxygen species (ROS) also increases and causes the rapid apoptotic death of activated cells, thereby facilitating T cell homeostasis. Nicotinamide (NAM) has previously been shown to enhance mitochondria quality and extend the replicative life span of human fibroblasts. In this study, we examined the effect of NAM on CD8(+) T cell activation. NAM treatment attenuated the increase of mitochondrial content and ROS in T cells activated by CD3/CD28 antibodies. This was accompanied by an accelerated and higher-level clonal expansion resulting from attenuated apoptotic death but not increased division of the activated cells. Attenuation of ROS-triggered pro-apoptotic events and upregulation of Bcl-2 expression appeared to be involved. Although cells activated in the presence of NAM exhibited compromised cytokine gene expression, our results suggest a means to augment the size of T cell expansion during activation without consuming their limited replicative potential.

Amino acid sources in the adult diet do not affect life span and fecundity in the fruit-feeding butterfly Bicyclus anynana.

PubMed

Molleman, Freerk; Ding, Jimin; Wang, Jane-Ling; Brakefield, Paul M; Carey, James R; Zwaan, Bas J

2008-08-01

1. In tropical forests, the adults of many butterfly species feed on fruits rather than nectar from flowers and have long life spans. Rotting fruit and nectar differ from each other in many respects, including sources of amino acids and microbial life. If amino acids in the adult diet can be used for reproduction, this may have facilitated the evolution of extended life spans in this guild.2. This issue was addressed by investigating effects of banana, yeast, and amino acids in the adult diet of the fruit-feeding butterfly Bicyclus anynana (Lepidoptera) on longevity and female reproductive output in two experiments.3. Results showed that in the fruit-feeding butterfly B. anynana: (i) banana juice, but not sliced banana or added amino acids extend life span compared with a sugar solution of similar composition; (ii) compared with this sugar solution, other cohorts (banana juice-amino acid enriched) did not have significantly higher reproductive outputs; (iii) yeast does not represent a valuable source of nutrients; (iv) caloric restriction may cause decreased life span and rate of reproduction; and (v) increased rates of reproduction have a life span cost.

Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring.

PubMed

Gribble, Kristin E; Jarvis, George; Bock, Martha; Mark Welch, David B

2014-08-01

While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve health span and life span. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Eternity in six hours: Intergalactic spreading of intelligent life and sharpening the Fermi paradox

NASA Astrophysics Data System (ADS)

Armstrong, Stuart; Sandberg, Anders

2013-08-01

The Fermi paradox is the discrepancy between the strong likelihood of alien intelligent life emerging (under a wide variety of assumptions) and the absence of any visible evidence for such emergence. In this paper, we extend the Fermi paradox to not only life in this galaxy, but to other galaxies as well. We do this by demonstrating that travelling between galaxies - indeed even launching a colonisation project for the entire reachable universe - is a relatively simple task for a star-spanning civilisation, requiring modest amounts of energy and resources. We start by demonstrating that humanity itself could likely accomplish such a colonisation project in the foreseeable future, should we want to. Given certain technological assumptions, such as improved automation, the task of constructing Dyson spheres, designing replicating probes, and launching them at distant galaxies, become quite feasible. We extensively analyse the dynamics of such a project, including issues of deceleration and collision with particles in space. Using similar methods, there are millions of galaxies that could have reached us by now. This results in a considerable sharpening of the Fermi paradox.

Sexual conflict, life span, and aging.

PubMed

Adler, Margo I; Bonduriansky, Russell

2014-06-17

The potential for sexual conflict to influence the evolution of life span and aging has been recognized for more than a decade, and recent work also suggests that variation in life span and aging can influence sexually antagonistic coevolution. However, empirical exploration of these ideas is only beginning. Here, we provide an overview of the ideas and evidence linking inter- and intralocus sexual conflicts with life span and aging. We aim to clarify the conceptual basis of this research program, examine the current state of knowledge, and suggest key questions for further investigation. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Increased production of mitochondrial reactive oxygen species and reduced adult life span in an insecticide-resistant strain of Anopheles gambiae

PubMed Central

Otali, Dennis; Novak, Robert J.; Wan, Wen; Bu, Su; Moellering, Douglas R.; De Luca, Maria

2014-01-01

Control of the malaria vector An. gambiae is still largely obtained through chemical intervention using pyrethroids, such as permethrin. However, strains of An. gambiae that are resistant to the toxic effects of pyrethroids have become widespread in several endemic areas over the last decade. The objective of this study was to assess differences in five life-history traits (larval developmental time and the body weight, fecundity, hatch rate, and longevity of adult females) and energy metabolism between a strain of An. gambiae that is resistant to permethrin (RSP), due to knockdown resistance and enhanced metabolic detoxification, and a permethrin susceptible strain reared under laboratory conditions. We also quantified the expression levels of five antioxidant enzyme genes: GSTe3, CAT, GPXH1, SOD1, and SOD2. We found that the RSP strain had a longer developmental time than the susceptible strain. Additionally, RSP adult females had higher wet body weight and increased water and glycogen levels. Compared to permethrin susceptible females, RSP females displayed reduced metabolic rate and mitochondrial coupling efficiency and higher mitochondrial ROS production. Furthermore, despite higher levels of GSTe3 and CAT transcripts, RSP females had a shorter adult life span than susceptible females. Collectively, these results suggest that permethrin resistance alleles might affect energy metabolism, oxidative stress, and adult survival of An. gambiae. However, because the strains used in this study differ in their genetic backgrounds, the results need to be interpreted with caution and replicated in other strains in order to have significant implications for malaria transmission and vector control. PMID:24555527

Defining wild-type life span in Caenorhabditis elegans.

PubMed

Gems, D; Riddle, D L

2000-05-01

The nematode Caenorhabditis elegans reproduces predominantly as a self-fertilizing hermaphrodite, and this drives laboratory populations to be homozygous at all genetic loci. Passaging of stocks can lead to fixation of spontaneous mutations, especially when the latter do not result in a selective disadvantage under laboratory conditions. Life span may be such a trait, since a comparison of six wild-type N2 lines derived from a common ancestor (but maintained separately in several laboratories) revealed four variants with median adult life spans ranging from 12.0 +/- 0.8 to 17.0 +/- 0.6 days at 20 degrees C. Fertility was also reduced in the two shortest-lived strains. We determined which life span most closely corresponds to that of the authentic wild type by two means. Firstly, N2 hermaphrodites were compared with seven C. elegans wild isolates. The latter were found to resemble only the longest-lived N2 strain. Comparison of male life spans of six lines also revealed additional strain variation. Secondly, life spans of F1 progeny issuing from crosses between N2 variants showed that short life spans were recessive, indicating that they result from loss-of-function mutations. We infer that the longest-lived N2 variant best resembles the original N2 isolate. This is the N2 male stock currently distributed by the Caenorhabditis Genetics Center.

Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats

PubMed Central

Kim, Dajeong; Kyung, Jangbeen; Park, Dongsun; Choi, Ehn-Kyoung; Kim, Kwang Sei; Shin, Kyungha; Lee, Hangyoung; Shin, Il Seob; Kang, Sung Keun

2015-01-01

Aging brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle-derived stem/progenitor cells extended the health span and life span of progeria mice, such effects in normal animals were not confirmed. Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or adipose tissue-derived mesenchymal stem cells (ADMSCs) (1 × 106 cells per rat) were intravenously transplanted to 10-month-old male F344 rats once a month throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally aging rats, extending life span by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule-associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass, and antioxidative capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both health span and life span, which could be a starting point for antiaging or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection. Significance This study demonstrates that repeated treatment with stem cells in normal animals has antiaging potential, extending health span and life span. Because antiaging and prolonged life span are issues currently of interest, these results are significant for readers and investigators. PMID:26315571

The Rate of Source Memory Decline across the Adult Life Span

ERIC Educational Resources Information Center

Cansino, Selene; Estrada-Manilla, Cinthya; Hernandez-Ramos, Evelia; Martinez-Galindo, Joyce Graciela; Torres-Trejo, Frine; Gomez-Fernandez, Tania; Ayala-Hernandez, Mariana; Osorio, David; Cedillo-Tinoco, Melisa; Garces-Flores, Lissete; Gomez-Melgarejo, Sandra; Beltran-Palacios, Karla; Guadalupe Garcia-Lazaro, Haydee; Garcia-Gutierrez, Fabiola; Cadena-Arenas, Yadira; Fernandez-Apan, Luisa; Bartschi, Andrea; Resendiz-Vera, Julieta; Rodriguez-Ortiz, Maria Dolores

2013-01-01

Previous studies have suggested that the ability to remember contextual information related to specific episodic experiences declines with advancing age; however, the exact moment in the adult life span when this deficit begins is still controversial. Source memory for spatial information was tested in a life span sample of 1,500 adults between…

Reduced Neuronal Transcription of Escargot, the Drosophila Gene Encoding a Snail-Type Transcription Factor, Promotes Longevity

PubMed Central

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

2018-01-01

In recent years, several genes involved in complex neuron specification networks have been shown to control life span. However, information on these genes is scattered, and studies to discover new neuronal genes and gene cascades contributing to life span control are needed, especially because of the recognized role of the nervous system in governing homeostasis, aging, and longevity. Previously, we demonstrated that several genes that encode RNA polymerase II transcription factors and that are involved in the development of the nervous system affect life span in Drosophila melanogaster. Among other genes, escargot (esg) was demonstrated to be causally associated with an increase in the life span of male flies. Here, we present new data on the role of esg in life span control. We show that esg affects the life spans of both mated and unmated males and females to varying degrees. By analyzing the survival and locomotion of the esg mutants, we demonstrate that esg is involved in the control of aging. We show that increased longevity is caused by decreased esg transcription. In particular, we demonstrate that esg knockdown in the nervous system increased life span, directly establishing the involvement of the neuronal esg function in life span control. Our data invite attention to the mechanisms regulating the esg transcription rate, which is changed by insertions of DNA fragments of different sizes downstream of the structural part of the gene, indicating the direction of further research. Our data agree with the previously made suggestion that alterations in gene expression during development might affect adult lifespan, due to epigenetic patterns inherited in cell lineages or predetermined during the development of the structural and functional properties of the nervous system. PMID:29760717

Experimental evolution reveals antagonistic pleiotropy in reproductive timing but not life span in Caenorhabditis elegans.

PubMed

Anderson, Jennifer L; Reynolds, Rose M; Morran, Levi T; Tolman-Thompson, Julie; Phillips, Patrick C

2011-12-01

Many mutations that dramatically extend life span in model organisms come with substantial fitness costs. Although these genetic manipulations provide valuable insight into molecular modulators of life span, it is currently unclear whether life-span extension is unavoidably linked to fitness costs. To examine this relationship, we evolved a genetically heterogeneous population of Caenorhabditis elegans for 47 generations, selecting for early fecundity. We asked whether an increase in early fecundity would necessitate a decrease in longevity or late fecundity (antagonistic pleiotropy). Caenorhabditis elegans experimentally evolved for increased early reproduction and decreased late reproduction but suffered no total fitness or life-span costs. Given that antagonistic pleiotropy among these traits has been previously demonstrated in some cases, we conclude that the genetic constraint is not absolute, that is, it is possible to uncouple longevity from early fecundity using genetic variation segregating within and among natural populations.

Herbal Supplement Extends Life Span Under Some Environmental Conditions and Boosts Stress Resistance

PubMed Central

Villeponteau, Bryant; Matsagas, Kennedy; Nobles, Amber C.; Rizza, Cristina; Horwitz, Marc; Benford, Gregory; Mockett, Robin J.

2015-01-01

Genetic studies indicate that aging is modulated by a great number of genetic pathways. We have used Drosophila longevity and stress assays to test a multipath intervention strategy. To carry out this strategy, we supplemented the flies with herbal extracts (SC100) that are predicted to modulate the expression of many genes involved in aging and stress resistance, such as mTOR, NOS, NF-KappaB, and VEGF. When flies were housed in large cages with SC100 added, daily mortality rates of both male and female flies were greatly diminished in mid to late life. Surprisingly, SC100 also stabilized midlife mortality rate increases so as to extend the maximum life span substantially beyond the limits previously reported for D. melanogaster. Under these conditions, SC100 also promoted robust resistance to partial starvation stress and to heat stress. Fertility was the same initially in both treated and control flies, but it became significantly higher in treated flies at older ages as the fertility of control flies declined. Mean and maximum life spans of flies in vials at the same test site were also extended by SC100, but the life spans were short in absolute terms. In contrast, at an independent test site where stress was minimized, the flies exhibited much longer mean life spans, but the survival curves became highly rectangular and the effects of SC100 on both mean and maximum life spans declined greatly or were abolished. The data indicate that SC100 is a novel herbal mix with striking effects on enhancing Drosophila stress resistance and life span in some environments, while minimizing mid to late life mortality rates. They also show that the environment and other factors can have transformative effects on both the length and distribution of survivorship, and on the ability of SC100 to extend the life span. PMID:25879540

How Genes Modulate Patterns of Aging-Related Changes on the Way to 100: Biodemographic Models and Methods in Genetic Analyses of Longitudinal Data

PubMed Central

Yashin, Anatoliy I.; Arbeev, Konstantin G.; Wu, Deqing; Arbeeva, Liubov; Kulminski, Alexander; Kulminskaya, Irina; Akushevich, Igor; Ukraintseva, Svetlana V.

2016-01-01

Background and Objective To clarify mechanisms of genetic regulation of human aging and longevity traits, a number of genome-wide association studies (GWAS) of these traits have been performed. However, the results of these analyses did not meet expectations of the researchers. Most detected genetic associations have not reached a genome-wide level of statistical significance, and suffered from the lack of replication in the studies of independent populations. The reasons for slow progress in this research area include low efficiency of statistical methods used in data analyses, genetic heterogeneity of aging and longevity related traits, possibility of pleiotropic (e.g., age dependent) effects of genetic variants on such traits, underestimation of the effects of (i) mortality selection in genetically heterogeneous cohorts, (ii) external factors and differences in genetic backgrounds of individuals in the populations under study, the weakness of conceptual biological framework that does not fully account for above mentioned factors. One more limitation of conducted studies is that they did not fully realize the potential of longitudinal data that allow for evaluating how genetic influences on life span are mediated by physiological variables and other biomarkers during the life course. The objective of this paper is to address these issues. Data and Methods We performed GWAS of human life span using different subsets of data from the original Framingham Heart Study cohort corresponding to different quality control (QC) procedures and used one subset of selected genetic variants for further analyses. We used simulation study to show that approach to combining data improves the quality of GWAS. We used FHS longitudinal data to compare average age trajectories of physiological variables in carriers and non-carriers of selected genetic variants. We used stochastic process model of human mortality and aging to investigate genetic influence on hidden biomarkers of aging and on dynamic interaction between aging and longevity. We investigated properties of genes related to selected variants and their roles in signaling and metabolic pathways. Results We showed that the use of different QC procedures results in different sets of genetic variants associated with life span. We selected 24 genetic variants negatively associated with life span. We showed that the joint analyses of genetic data at the time of bio-specimen collection and follow up data substantially improved significance of associations of selected 24 SNPs with life span. We also showed that aging related changes in physiological variables and in hidden biomarkers of aging differ for the groups of carriers and non-carriers of selected variants. Conclusions . The results of these analyses demonstrated benefits of using biodemographic models and methods in genetic association studies of these traits. Our findings showed that the absence of a large number of genetic variants with deleterious effects may make substantial contribution to exceptional longevity. These effects are dynamically mediated by a number of physiological variables and hidden biomarkers of aging. The results of these research demonstrated benefits of using integrative statistical models of mortality risks in genetic studies of human aging and longevity. PMID:27773987

Learning From Leaders: Life-span Trends in Olympians and Supercentenarians.

PubMed

Antero-Jacquemin, Juliana da Silva; Berthelot, Geoffroy; Marck, Adrien; Noirez, Philippe; Latouche, Aurélien; Toussaint, Jean-François

2015-08-01

Life-span trends progression has worldwide practical implications as it may affect the sustainability of modern societies. We aimed to describe the secular life-span trends of populations with a propensity to live longer-Olympians and supercentenarians-under two hypotheses: an ongoing life-span extension versus a biologic "probabilistic barrier" limiting further progression. In a study of life-span densities (total number of life durations per birth date), we analyzed 19,012 Olympians and 1,205 supercentenarians deceased between 1900 and 2013. Among most Olympians, we observed a trend toward increased life duration. This trend, however, decelerates at advanced ages leveling off with the upper values with a perennial gap between Olympians and supercentenarians during the whole observation period. Similar tendencies are observed among supercentenarians, and over the last years, a plateau attests to a stable longevity pattern among the longest-lived humans. The common trends between Olympians and supercentenarians indicate similar mortality pressures over both populations that increase with age, scenario better explained by a biologic "barrier" forecast. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America.

The cost of the muse: poets die young.

PubMed

Kaufman, James C

2003-11-01

Although several investigations have found that poets tend to die younger than other types of writers, these studies often do not take into account variables of gender and culture. This study examines 1,987 deceased writers from four different cultures: American, Chinese, Turkish, and Eastern European. Both male and female poets had the shortest life spans of all four types of writers (fiction writers, poets, playwrights, and non-fiction writers), and poets had the shortest life spans in three of the four cultures (and the second shortest life span among Eastern European writers). Possible reasons for the poet's shorter life span are then discussed.

Individual differences in personality change across the adult life span.

PubMed

Schwaba, Ted; Bleidorn, Wiebke

2018-06-01

A precise and comprehensive description of personality continuity and change across the life span is the bedrock upon which theories of personality development are built. Little research has quantified the degree to which individuals deviate from mean-level developmental trends. In this study, we addressed this gap by examining individual differences in personality trait change across the life span. Data came from a nationally representative sample of 9,636 Dutch participants who provided Big Five self-reports at five assessment waves across 7 years. We divided our sample into 14 age groups (ages 16-84 at initial measurement) and estimated latent growth curve models to describe individual differences in personality change across the study period for each trait and age group. Across the adult life span, individual differences in personality change were small but significant until old age. For Openness, Conscientiousness, Extraversion, and Agreeableness, individual differences in change were most pronounced in emerging adulthood and decreased throughout midlife and old age. For Emotional Stability, individual differences in change were relatively consistent across the life span. These results inform theories of life span development and provide future directions for research on the causes and conditions of personality change. © 2017 Wiley Periodicals, Inc.

Effect of Ala-Glu-Asp-Gly peptide on life span and development of spontaneous tumors in female rats exposed to different illumination regimes.

PubMed

Vinogradova, I A; Bukalev, A V; Zabezhinski, M A; Semenchenko, A V; Khavinson, V Kh; Anisimov, V N

2007-12-01

The effects of Ala-Glu-Asp-Gly peptide (Epithalon) on the life span and development of spontaneous tumors were studied in female rats exposed to standard, natural for North-Western Russia, and constant illumination. The mean life span of animals exposed to constant or natural illumination decreased by 13.5 and 25.5%, the maximum by 9 and 7 months, respectively, and spontaneous tumors developed much more rapidly than in animals living under conditions of the standard light regimen. Epithalon (0.1 microg daily 5 times a week from the age of 4 months) did not change the life span of rats living under conditions of standard day/night regimen, while in rats exposed to the natural and constant light it promoted prolongation of the maximum life span by 95 and 24 days, respectively. Epithalon prolonged the mean life span of the last 10% of rats exposed to natural and constant illumination, treated with Epithalon, by 137 and 43 days, respectively. This peptide exhibited virtually no effect on the development of spontaneous tumors in rats exposed to standard and constant illumination, but significantly inhibited their development in rats exposed to natural light.

Life Span Evolution in Eusocial Workers—A Theoretical Approach to Understanding the Effects of Extrinsic Mortality in a Hierarchical System

PubMed Central

Kramer, Boris H.; Schaible, Ralf

2013-01-01

While the extraordinary life span of queens and division of labor in eusocial societies have been well studied, it is less clear which selective forces act on the short life span of workers. The disparity of life span between the queen and the workers is linked to a basic issue in sociobiology: How are the resources in a colony allocated between colony maintenance and reproduction? Resources for somatic maintenance of the colony can either be invested into quality or quantity of workers. Here, we present a theoretical optimization model that uses a hierarchical trade-off within insect colonies and extrinsic mortality to explain how different aging phenotypes could have evolved to keep resources secure in the colony. The model points to the significance of two factors. First, any investment that would generate a longer intrinsic life span for workers is lost if the individual dies from external causes while foraging. As a consequence, risky environments favor the evolution of workers with a shorter life span. Second, shorter-lived workers require less investment than long-lived ones, allowing the colony to allocate these resources to sexual reproduction or colony growth. PMID:23596527

Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality.

PubMed

Eppinga, Ruben N; Hagemeijer, Yanick; Burgess, Stephen; Hinds, David A; Stefansson, Kari; Gudbjartsson, Daniel F; van Veldhuisen, Dirk J; Munroe, Patricia B; Verweij, Niek; van der Harst, Pim

2016-12-01

Resting heart rate is a heritable trait correlated with life span. Little is known about the genetic contribution to resting heart rate and its relationship with mortality. We performed a genome-wide association discovery and replication analysis starting with 19.9 million genetic variants and studying up to 265,046 individuals to identify 64 loci associated with resting heart rate (P < 5 × 10 -8 ); 46 of these were novel. We then used the genetic variants identified to study the association between resting heart rate and all-cause mortality. We observed that a genetically predicted resting heart rate increase of 5 beats per minute was associated with a 20% increase in mortality risk (hazard ratio 1.20, 95% confidence interval 1.11-1.28, P = 8.20 × 10 -7 ) translating to a reduction in life expectancy of 2.9 years for males and 2.6 years for females. Our findings provide evidence for shared genetic predictors of resting heart rate and all-cause mortality.

Cranberry interacts with dietary macronutrients to promote healthy aging in Drosophila.

PubMed

Wang, Cecilia; Yolitz, Jason; Alberico, Thomas; Laslo, Mara; Sun, Yaning; Wheeler, Charles T; Sun, Xiaoping; Zou, Sige

2014-08-01

Botanicals possess numerous bioactivities, and some promote healthy aging. Dietary macronutrients are major determinants of life span. The interaction between botanicals and macronutrients that modulates life span is not well understood. Here, we investigated the effect of a cranberry-containing botanical on life span and the influence of macronutrients on the longevity-related effect of cranberry in Drosophila. Flies were supplemented with cranberry on three dietary conditions: standard, high sugar-low protein, and low sugar-high protein diets. We found that cranberry slightly extended life span in males fed with the low sugar-high protein diet but not with other diets. Cranberry extended life span in females fed with the standard diet and more prominently the high sugar-low protein diet but not with the low sugar-high protein diet. Life-span extension was associated with increased reproduction and higher expression of oxidative stress and heat shock response genes. Moreover, cranberry improved survival of sod1 knockdown and dfoxo mutant flies but did not increase wild-type fly's resistance to acute oxidative stress. Cranberry slightly extended life span in flies fed with a high-fat diet. These findings suggest that cranberry promotes healthy aging by increasing stress responsiveness. Our study reveals an interaction of cranberry with dietary macronutrients and stresses the importance of considering diet composition in designing interventions for promoting healthy aging. Published by Oxford University Press on behalf of the Gerontological Society of America 2013.

A test of life-history theories of immune defence in two ecotypes of the garter snake, Thamnophis elegans.

PubMed

Sparkman, Amanda Marie; Palacios, Maria Gabriela

2009-11-01

1. Life-history theorists have long observed that fast growth and high reproduction tend to be associated with short life span, suggesting that greater investment in such traits may trade off with self-maintenance. The immune system plays an integral role in self-maintenance and has been proposed as a mediator of life-history trade-offs. 2. Ecoimmunologists have predicted that fast-living organisms should rely more heavily on constitutive innate immunity than slow-living organisms, as constitutive innate defences are thought to be relatively inexpensive to develop and can provide a rapid, general response to pathogens. 3. We present the first study to examine this hypothesis in an ectothermic vertebrate, by testing for differences in three aspects of constitutive innate immunity in replicate populations of two life-history ecotypes of the garter snake Thamnophis elegans, one fast-living and one slow-living. 4. As predicted, free-ranging snakes from the fast-living ecotype had higher levels of all three measures of constitutive innate immunity than the slow-living ecotype. These differences in immunity were not explained by parasite loads measured. Furthermore, both ecotypes exhibited a positive relationship between innate immunity and body size/age, which we discuss in the context of ectotherm physiology and ecotype differences in developmental rates.

Health Span-Extending Activity of Human Amniotic Membrane- and Adipose Tissue-Derived Stem Cells in F344 Rats.

PubMed

Kim, Dajeong; Kyung, Jangbeen; Park, Dongsun; Choi, Ehn-Kyoung; Kim, Kwang Sei; Shin, Kyungha; Lee, Hangyoung; Shin, Il Seob; Kang, Sung Keun; Ra, Jeong Chan; Kim, Yun-Bae

2015-10-01

Aging brings about the progressive decline in cognitive function and physical activity, along with losses of stem cell population and function. Although transplantation of muscle-derived stem/progenitor cells extended the health span and life span of progeria mice, such effects in normal animals were not confirmed. Human amniotic membrane-derived mesenchymal stem cells (AMMSCs) or adipose tissue-derived mesenchymal stem cells (ADMSCs) (1×10(6) cells per rat) were intravenously transplanted to 10-month-old male F344 rats once a month throughout their lives. Transplantation of AMMSCs and ADMSCs improved cognitive and physical functions of naturally aging rats, extending life span by 23.4% and 31.3%, respectively. The stem cell therapy increased the concentration of acetylcholine and recovered neurotrophic factors in the brain and muscles, leading to restoration of microtubule-associated protein 2, cholinergic and dopaminergic nervous systems, microvessels, muscle mass, and antioxidative capacity. The results indicate that repeated transplantation of AMMSCs and ADMSCs elongate both health span and life span, which could be a starting point for antiaging or rejuvenation effects of allogeneic or autologous stem cells with minimum immune rejection. This study demonstrates that repeated treatment with stem cells in normal animals has antiaging potential, extending health span and life span. Because antiaging and prolonged life span are issues currently of interest, these results are significant for readers and investigators. ©AlphaMed Press.

Dietary restriction in two rotifer species: the effect of the length of food deprivation on life span and reproduction.

PubMed

Weithoff, Guntram

2007-08-01

According to resource allocation theory, animals face a trade off between the allocation of resources into reproduction and into individual growth/maintenance. This trade off is reinforced when food conditions decline. It is well established in biological research that many animals increase their life span when food is in suboptimal supply for growth and/or reproduction. Such a situation of reduced food availability is called dietary restriction. An increase in life span under dietary restricted conditions is seen as a strategy to tolerate periods of food shortage so that the animals can start reproduction again when food is in greater supply. In this study, the effect of dietary restriction on life span and reproduction in two rotifer species, Cephalodella sp. and Elosa worallii, was investigated using life table experiments. The food concentration under dietary restricted conditions was below the threshold for population growth. It was (1) tested whether the rotifers start reproduction again after food replenishment, and (2) estimated whether the time scale of dietary restricted conditions is relevant for the persistence of a population in the field. Only E. worallii responded to dietary restriction with an increase in life span at the expense of reproduction. After replenishment of food, E. worallii started to reproduce again within 1 day. With an increase in the duration of dietary restricted conditions of up to 15 days, which is longer than the median life span of E. worallii under food saturation, the life span increased and the life time reproduction decreased. These results suggest that in a temporally (or spatially) variable environment, some rotifer populations can persist even during long periods of severe food deprivation.

Leaf life span and the mobility of "non-mobile" mineral nutrients - the case of boron in conifers

Treesearch

Pedro J. Aphalo; Anna W. Schoettle; Tarja Lehto

2002-01-01

Nutrient conservation is considered important for the adaptation of plants to infertile environments. The importance of leaf life spans in controlling mean residence time of nutrients in plants has usually been analyzed in relation to nutrients that can be retranslocated within the plant. Longer leaf life spans increase the mean residence time of all mineral...

The Development of Memory Efficiency and Value-Directed Remembering across the Life Span: A Cross-Sectional Study of Memory and Selectivity

ERIC Educational Resources Information Center

Castel, Alan D.; Humphreys, Kathryn L.; Lee, Steve S.; Galvan, Adriana; Balota, David A.; McCabe, David P.

2011-01-01

Although attentional control and memory change considerably across the life span, no research has examined how the ability to strategically remember important information (i.e., value-directed remembering) changes from childhood to old age. The present study examined this in different age groups across the life span (N = 320, 5-96 years old). A…

Transient compartmentalization of RNA replicators prevents extinction due to parasites.

PubMed

Matsumura, Shigeyoshi; Kun, Ádám; Ryckelynck, Michael; Coldren, Faith; Szilágyi, András; Jossinet, Fabrice; Rick, Christian; Nghe, Philippe; Szathmáry, Eörs; Griffiths, Andrew D

2016-12-09

The appearance of molecular replicators (molecules that can be copied) was probably a critical step in the origin of life. However, parasitic replicators would take over and would have prevented life from taking off unless the replicators were compartmentalized in reproducing protocells. Paradoxically, control of protocell reproduction would seem to require evolved replicators. We show here that a simpler population structure, based on cycles of transient compartmentalization (TC) and mixing of RNA replicators, is sufficient to prevent takeover by parasitic mutants. TC tends to select for ensembles of replicators that replicate at a similar rate, including a diversity of parasites that could serve as a source of opportunistic functionality. Thus, TC in natural, abiological compartments could have allowed life to take hold. Copyright © 2016, American Association for the Advancement of Science.

A universal expression/silencing vector in plants.

PubMed

Peretz, Yuval; Mozes-Koch, Rita; Akad, Fuad; Tanne, Edna; Czosnek, Henryk; Sela, Ilan

2007-12-01

A universal vector (IL-60 and auxiliary constructs), expressing or silencing genes in every plant tested to date, is described. Plants that have been successfully manipulated by the IL-60 system include hard-to-manipulate species such as wheat (Triticum duram), pepper (Capsicum annuum), grapevine (Vitis vinifera), citrus, and olive (Olea europaea). Expression or silencing develops within a few days in tomato (Solanum lycopersicum), wheat, and most herbaceous plants and in up to 3 weeks in woody trees. Expression, as tested in tomato, is durable and persists throughout the life span of the plant. The vector is, in fact, a disarmed form of Tomato yellow leaf curl virus, which is applied as a double-stranded DNA and replicates as such. However, the disarmed virus does not support rolling-circle replication, and therefore viral progeny single-stranded DNA is not produced. IL-60 does not integrate into the plant's genome, and the construct, including the expressed gene, is not heritable. IL-60 is not transmitted by the Tomato yellow leaf curl virus's natural insect vector. In addition, artificial satellites were constructed that require a helper virus for replication, movement, and expression. With IL-60 as the disarmed helper "virus," transactivation occurs, resulting in an inducible expressing/silencing system. The system's potential is demonstrated by IL-60-derived suppression of a viral-silencing suppressor of Grapevine virus A, resulting in Grapevine virus A-resistant/tolerant plants.

Connecting Life Span Development with the Sociology of the Life Course: A New Direction.

PubMed

Gilleard, Chris; Higgs, Paul

2016-04-01

The life course has become a topic of growing interest within the social sciences. Attempts to link this sub-discipline with life span developmental psychology have been called for but with little sign of success. In this paper, we seek to address three interlinked issues concerning the potential for a more productive interchange between life course sociology and life span psychology. The first is to try to account for the failure of these two sub-disciplines to achieve any deepening engagement with each other, despite the long-expressed desirability of that goal; the second is to draw attention to the scope for enriching the sociology of the life course through Erik Erikson's model of life span development; and the last is the potential for linking Eriksonian theory with current debates within mainstream sociology about the processes involved in 'individualisation' and 'self-reflexivity' as an alternative entry point to bring together these two fields of work.

Connecting Life Span Development with the Sociology of the Life Course: A New Direction

PubMed Central

Gilleard, Chris; Higgs, Paul

2015-01-01

The life course has become a topic of growing interest within the social sciences. Attempts to link this sub-discipline with life span developmental psychology have been called for but with little sign of success. In this paper, we seek to address three interlinked issues concerning the potential for a more productive interchange between life course sociology and life span psychology. The first is to try to account for the failure of these two sub-disciplines to achieve any deepening engagement with each other, despite the long-expressed desirability of that goal; the second is to draw attention to the scope for enriching the sociology of the life course through Erik Erikson’s model of life span development; and the last is the potential for linking Eriksonian theory with current debates within mainstream sociology about the processes involved in ‘individualisation’ and ‘self-reflexivity’ as an alternative entry point to bring together these two fields of work. PMID:27041774

Differential Regulation of Telomerase Reverse Transcriptase Promoter Activation and Protein Degradation by Histone Deacetylase Inhibition.

PubMed

Qing, Hua; Aono, Jun; Findeisen, Hannes M; Jones, Karrie L; Heywood, Elizabeth B; Bruemmer, Dennis

2016-06-01

Telomerase reverse transcriptase (TERT) maintains telomeres and is rate limiting for replicative life span. While most somatic tissues silence TERT transcription resulting in telomere shortening, cells derived from cancer or cardiovascular diseases express TERT and activate telomerase. In the present study, we demonstrate that histone deacetylase (HDAC) inhibition induces TERT transcription and promoter activation. At the protein level in contrast, HDAC inhibition decreases TERT protein abundance through enhanced degradation, which decreases telomerase activity and induces senescence. Finally, we demonstrate that HDAC inhibition decreases TERT expression during vascular remodeling in vivo. These data illustrate a differential regulation of TERT transcription and protein stability by HDAC inhibition and suggest that TERT may constitute an important target for the anti-proliferative efficacy of HDAC inhibitors. © 2015 Wiley Periodicals, Inc.

Decision-making heuristics and biases across the life span.

PubMed

Strough, Jonell; Karns, Tara E; Schlosnagle, Leo

2011-10-01

We outline a contextual and motivational model of judgment and decision-making (JDM) biases across the life span. Our model focuses on abilities and skills that correspond to deliberative, experiential, and affective decision-making processes. We review research that addresses links between JDM biases and these processes as represented by individual differences in specific abilities and skills (e.g., fluid and crystallized intelligence, executive functioning, emotion regulation, personality traits). We focus on two JDM biases-the sunk-cost fallacy (SCF) and the framing effect. We trace the developmental trajectory of each bias from preschool through middle childhood, adolescence, early adulthood, and later adulthood. We conclude that life-span developmental trajectories differ depending on the bias investigated. Existing research suggests relative stability in the framing effect across the life span and decreases in the SCF with age, including in later life. We highlight directions for future research on JDM biases across the life span, emphasizing the need for process-oriented research and research that increases our understanding of JDM biases in people's everyday lives. © 2011 New York Academy of Sciences.

Decision-making heuristics and biases across the life span

PubMed Central

Strough, JoNell; Karns, Tara E.; Schlosnagle, Leo

2013-01-01

We outline a contextual and motivational model of judgment and decision-making (JDM) biases across the life span. Our model focuses on abilities and skills that correspond to deliberative, experiential, and affective decision-making processes. We review research that addresses links between JDM biases and these processes as represented by individual differences in specific abilities and skills (e.g., fluid and crystallized intelligence, executive functioning, emotion regulation, personality traits). We focus on two JDM biases—the sunk-cost fallacy (SCF) and the framing effect. We trace the developmental trajectory of each bias from preschool through middle childhood, adolescence, early adulthood, and later adulthood. We conclude that life-span developmental trajectories differ depending on the bias investigated. Existing research suggests relative stability in the framing effect across the life span and decreases in the SCF with age, including in later life. We highlight directions for future research on JDM biases across the life span, emphasizing the need for process-oriented research and research that increases our understanding of JDM biases in people’s everyday lives. PMID:22023568

Autophagy-mediated longevity is modulated by lipoprotein biogenesis

PubMed Central

Seah, Nicole E.; de Magalhaes Filho, C. Daniel; Petrashen, Anna P.; Henderson, Hope R.; Laguer, Jade; Gonzalez, Julissa; Dillin, Andrew; Hansen, Malene; Lapierre, Louis R.

2016-01-01

ABSTRACT Autophagy-dependent longevity models in C. elegans display altered lipid storage profiles, but the contribution of lipid distribution to life-span extension is not fully understood. Here we report that lipoprotein production, autophagy and lysosomal lipolysis are linked to modulate life span in a conserved fashion. We find that overexpression of the yolk lipoprotein VIT/vitellogenin reduces the life span of long-lived animals by impairing the induction of autophagy-related and lysosomal genes necessary for longevity. Accordingly, reducing vitellogenesis increases life span via induction of autophagy and lysosomal lipolysis. Life-span extension due to reduced vitellogenesis or enhanced lysosomal lipolysis requires nuclear hormone receptors (NHRs) NHR-49 and NHR-80, highlighting novel roles for these NHRs in lysosomal lipid signaling. In dietary-restricted worms and mice, expression of VIT and hepatic APOB (apolipoprotein B), respectively, are significantly reduced, suggesting a conserved longevity mechanism. Altogether, our study demonstrates that lipoprotein biogenesis is an important mechanism that modulates aging by impairing autophagy and lysosomal lipolysis. PMID:26671266

Life span effects of Hypericum perforatum extracts on Caenorhabditis elegans under heat stress.

PubMed

Kılıçgün, Hasan; Göksen, Gülden

2012-10-01

The beneficial effects of antioxidants in plants are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary antioxidants are beneficial in whole animals' life span or not. To address this question, under heat stress (35°C), Hypericum perforatum was extracted with petroleum ether and the nematodes Caenorhabditis elegans exposed to three different extract concentrations (1mg/mL, 0.1mg/mL, 0.01mg/mL) of H. perforatum. We report that Hypericum perforatum extracts did not increase life span and slow aging related increase in C. elegans. Moreover, one fraction (1mg/mL) increased declines of C. elegans life span and thermotolerance. Given this mounting evidence for life span role of H. perforatum in the presence of heat stress in vivo, the question whether H. perforatum acts as a prooxidant or an antioxidant in vivo under heat stress arises.

Life span effects of Hypericum perforatum extracts on Caenorhabditis elegans under heat stress

PubMed Central

Kılıçgün, Hasan; Göksen, Gülden

2012-01-01

Background: The beneficial effects of antioxidants in plants are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary antioxidants are beneficial in whole animals’ life span or not. Materials and Methods: To address this question, under heat stress (35°C), Hypericum perforatum was extracted with petroleum ether and the nematodes Caenorhabditis elegans exposed to three different extract concentrations (1mg/mL, 0.1mg/mL, 0.01mg/mL) of H. perforatum. Results: We report that Hypericum perforatum extracts did not increase life span and slow aging related increase in C. elegans. Moreover, one fraction (1mg/mL) increased declines of C. elegans life span and thermotolerance. Conclusion: Given this mounting evidence for life span role of H. perforatum in the presence of heat stress in vivo, the question whether H. perforatum acts as a prooxidant or an antioxidant in vivo under heat stress arises. PMID:24082638

Paternal smoking habits affect the reproductive life span of daughters.

PubMed

Fukuda, Misao; Fukuda, Kiyomi; Shimizu, Takashi; Nobunaga, Miho; Andersen, Elisabeth Wreford; Byskov, Anne Grete; Andersen, Claus Yding

2011-06-30

The present study assessed whether the smoking habits of fathers around the time of conception affected the period in which daughters experienced menstrual cycles (i.e., the reproductive life span). The study revealed that the smoking habits of the farther shortened the daughters' reproductive life span compared with daughters whose fathers did not smoke. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Structural covariance networks across the life span, from 6 to 94 years of age.

PubMed

DuPre, Elizabeth; Spreng, R Nathan

2017-10-01

Structural covariance examines covariation of gray matter morphology between brain regions and across individuals. Despite significant interest in the influence of age on structural covariance patterns, no study to date has provided a complete life span perspective-bridging childhood with early, middle, and late adulthood-on the development of structural covariance networks. Here, we investigate the life span trajectories of structural covariance in six canonical neurocognitive networks: default, dorsal attention, frontoparietal control, somatomotor, ventral attention, and visual. By combining data from five open-access data sources, we examine the structural covariance trajectories of these networks from 6 to 94 years of age in a sample of 1,580 participants. Using partial least squares, we show that structural covariance patterns across the life span exhibit two significant, age-dependent trends. The first trend is a stable pattern whose integrity declines over the life span. The second trend is an inverted-U that differentiates young adulthood from other age groups. Hub regions, including posterior cingulate cortex and anterior insula, appear particularly influential in the expression of this second age-dependent trend. Overall, our results suggest that structural covariance provides a reliable definition of neurocognitive networks across the life span and reveal both shared and network-specific trajectories.

ω-6 Polyunsaturated fatty acids extend life span through the activation of autophagy

PubMed Central

O'Rourke, Eyleen J.; Kuballa, Petric; Xavier, Ramnik; Ruvkun, Gary

2013-01-01

Adaptation to nutrient scarcity depends on the activation of metabolic programs to efficiently use internal reserves of energy. Activation of these programs in abundant food regimens can extend life span. However, the common molecular and metabolic changes that promote adaptation to nutritional stress and extend life span are mostly unknown. Here we present a response to fasting, enrichment of ω-6 polyunsaturated fatty acids (PUFAs), which promotes starvation resistance and extends Caenorhabditis elegans life span. Upon fasting, C. elegans induces the expression of a lipase, which in turn leads to an enrichment of ω-6 PUFAs. Supplementing C. elegans culture media with these ω-6 PUFAs increases their resistance to starvation and extends their life span in conditions of food abundance. Supplementation of C. elegans or human epithelial cells with these ω-6 PUFAs activates autophagy, a cell recycling mechanism that promotes starvation survival and slows aging. Inactivation of C. elegans autophagy components reverses the increase in life span conferred by supplementing the C. elegans diet with these fasting-enriched ω-6 PUFAs. We propose that the salubrious effects of dietary supplementation with ω-3/6 PUFAs (fish oils) that have emerged from epidemiological studies in humans may be due to a similar activation of autophagic programs. PMID:23392608

Genes that regulate both development and longevity in Caenorhabditis elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larsen, P.L.; Albert, P.S.; Riddle, D.L.

1995-04-01

The nematode Caenorhabditis elegans responds to conditions of overcrowding and limited food by arresting development as a dauer larva. Genetic analysis of mutations that alter dauer larva formation (daf mutations) is presented along with an updated genetic pathway for dauer vs. nondauer development. Mutations in the daf-2 and daf-23 genes double adult life span, whereas mutations in four other dauer-constitutive genes positioned in a separate branch of this pathway (daf-1, daf-4, daf-7 and daf-8) do not. The increased life spans are suppressed completely by a daf-16 mutation and partially in a daf-2; daf-18 double mutant. A genetic pathway for determinationmore » of adult life span is presented based on the same strains and growth conditions used to characterize Daf phenotypes. Both dauer larva formation and adult life span are affected in daf-2; daf-12 double mutants in an allele-specific manner. Mutations in daf-12 do not extend adult life span, but certain combinations of daf-2 and daf-12 mutant alleles nearly quadruple it. This synergistic effect, which does not equivalently extend the fertile period, is the largest genetic extension of life span yet observed in a metazoan. 47 refs., 7 figs., 5 tabs.« less

Genome-wide screen in Saccharomyces cerevisiae identifies vacuolar protein sorting, autophagy, biosynthetic, and tRNA methylation genes involved in life span regulation.

PubMed

Fabrizio, Paola; Hoon, Shawn; Shamalnasab, Mehrnaz; Galbani, Abdulaye; Wei, Min; Giaever, Guri; Nislow, Corey; Longo, Valter D

2010-07-15

The study of the chronological life span of Saccharomyces cerevisiae, which measures the survival of populations of non-dividing yeast, has resulted in the identification of homologous genes and pathways that promote aging in organisms ranging from yeast to mammals. Using a competitive genome-wide approach, we performed a screen of a complete set of approximately 4,800 viable deletion mutants to identify genes that either increase or decrease chronological life span. Half of the putative short-/long-lived mutants retested from the primary screen were confirmed, demonstrating the utility of our approach. Deletion of genes involved in vacuolar protein sorting, autophagy, and mitochondrial function shortened life span, confirming that respiration and degradation processes are essential for long-term survival. Among the genes whose deletion significantly extended life span are ACB1, CKA2, and TRM9, implicated in fatty acid transport and biosynthesis, cell signaling, and tRNA methylation, respectively. Deletion of these genes conferred heat-shock resistance, supporting the link between life span extension and cellular protection observed in several model organisms. The high degree of conservation of these novel yeast longevity determinants in other species raises the possibility that their role in senescence might be conserved.

Structural covariance networks across the life span, from 6 to 94 years of age

PubMed Central

DuPre, Elizabeth; Spreng, R. Nathan

2017-01-01

Structural covariance examines covariation of gray matter morphology between brain regions and across individuals. Despite significant interest in the influence of age on structural covariance patterns, no study to date has provided a complete life span perspective—bridging childhood with early, middle, and late adulthood—on the development of structural covariance networks. Here, we investigate the life span trajectories of structural covariance in six canonical neurocognitive networks: default, dorsal attention, frontoparietal control, somatomotor, ventral attention, and visual. By combining data from five open-access data sources, we examine the structural covariance trajectories of these networks from 6 to 94 years of age in a sample of 1,580 participants. Using partial least squares, we show that structural covariance patterns across the life span exhibit two significant, age-dependent trends. The first trend is a stable pattern whose integrity declines over the life span. The second trend is an inverted-U that differentiates young adulthood from other age groups. Hub regions, including posterior cingulate cortex and anterior insula, appear particularly influential in the expression of this second age-dependent trend. Overall, our results suggest that structural covariance provides a reliable definition of neurocognitive networks across the life span and reveal both shared and network-specific trajectories. PMID:29855624

Metabotypes with properly functioning mitochondria and anti-inflammation predict extended productive life span in dairy cows

PubMed Central

Huber, K.; Dänicke, S.; Rehage, J.; Sauerwein, H.; Otto, W.; Rolle-Kampczyk, U.; von Bergen, M.

2016-01-01

The failure to adapt metabolism to the homeorhetic demands of lactation is considered as a main factor in reducing the productive life span of dairy cows. The so far defined markers of production performance and metabolic health in dairy cows do not predict the length of productive life span satisfyingly. This study aimed to identify novel pathways and biomarkers related to productive life in dairy cows by means of (targeted) metabolomics. In a longitudinal study from 42 days before up to 100 days after parturition, we identified metabolites such as long-chain acylcarnitines and biogenic amines associated with extended productive life spans. These metabolites are mainly secreted by the liver and depend on the functionality of hepatic mitochondria. The concentrations of biogenic amines and some acylcarnitines differed already before the onset of lactation thus indicating their predictive potential for continuation or early ending of productive life. PMID:27089826

Metabotypes with properly functioning mitochondria and anti-inflammation predict extended productive life span in dairy cows.

PubMed

Huber, K; Dänicke, S; Rehage, J; Sauerwein, H; Otto, W; Rolle-Kampczyk, U; von Bergen, M

2016-04-19

The failure to adapt metabolism to the homeorhetic demands of lactation is considered as a main factor in reducing the productive life span of dairy cows. The so far defined markers of production performance and metabolic health in dairy cows do not predict the length of productive life span satisfyingly. This study aimed to identify novel pathways and biomarkers related to productive life in dairy cows by means of (targeted) metabolomics. In a longitudinal study from 42 days before up to 100 days after parturition, we identified metabolites such as long-chain acylcarnitines and biogenic amines associated with extended productive life spans. These metabolites are mainly secreted by the liver and depend on the functionality of hepatic mitochondria. The concentrations of biogenic amines and some acylcarnitines differed already before the onset of lactation thus indicating their predictive potential for continuation or early ending of productive life.

Trehalose extends longevity in the nematode Caenorhabditis elegans.

PubMed

Honda, Yoko; Tanaka, Masashi; Honda, Shuji

2010-08-01

Trehalose is a disaccharide of glucose found in diverse organisms and is suggested to act as a stress protectant against heat, cold, desiccation, anoxia, and oxidation. Here, we demonstrate that treatment of Caenorhabditis elegans with trehalose starting from the young-adult stage extended the mean life span by over 30% without any side effects. Surprisingly, trehalose treatment starting even from the old-adult stage shortly thereafter retarded the age-associated decline in survivorship and extended the remaining life span by 60%. Demographic analyses of age-specific mortality rates revealed that trehalose extended the life span by lowering age-independent vulnerability. Moreover, trehalose increased the reproductive span and retarded the age-associated decrease in pharyngeal-pumping rate and the accumulation of lipofuscin autofluorescence. Trehalose also enhanced thermotolerance and reduced polyglutamine aggregation. These results suggest that trehalose suppressed aging by counteracting internal or external stresses that disrupt protein homeostasis. On the other hand, the life span-extending effect of trehalose was abolished in long-lived insulin/IGF-1-like receptor (daf-2) mutants. RNA interference-mediated inactivation of the trehalose-biosynthesis genes trehalose-6-phosphate synthase-1 (tps-1) and tps-2, which are known to be up-regulated in daf-2 mutants, decreased the daf-2 life span. These findings indicate that a reduction in insulin/IGF-1-like signaling extends life span, at least in part, through the aging-suppressor function of trehalose. Trehalose may be a lead compound for potential nutraceutical intervention of the aging process.

Information-Theoretic Considerations Concerning the Origin of Life

NASA Astrophysics Data System (ADS)

Adami, Christoph

2015-09-01

Research investigating the origins of life usually either focuses on exploring possible life-bearing chemistries in the pre-biotic Earth, or else on synthetic approaches. Comparatively little work has explored fundamental issues concerning the spontaneous emergence of life using only concepts (such as information and evolution) that are divorced from any particular chemistry. Here, I advocate studying the probability of spontaneous molecular self-replication as a function of the information contained in the replicator, and the environmental conditions that might enable this emergence. I show (under certain simplifying assumptions) that the probability to discover a self-replicator by chance depends exponentially on the relative rate of formation of the monomers. If the rate at which monomers are formed is somewhat similar to the rate at which they would occur in a self-replicating polymer, the likelihood to discover such a replicator by chance is increased by many orders of magnitude. I document such an increase in searches for a self-replicator within the digital life system avida.

ERK1/2 signaling mediated naringin-induced osteogenic differentiation of immortalized human periodontal ligament stem cells.

PubMed

Wei, Kai; Xie, Yuansheng; Chen, Tianyu; Fu, Bo; Cui, Shaoyuan; Wang, Yan; Cai, Guangyan; Chen, Xiangmei

2017-07-29

Periodontal ligament stem cells (PDLSCs) are promising tools for the investigations of cell differentiation and bone regeneration. However, the limited life span significantly restricts their usefulness. In this study, we established an immortalized PDLSC cell line by the introduction of Bmi1 (PDLSC-Bmi1). Several genes related to cell cycle, cell replication and stemness were found to be changed with the overexpression of Bmi1. Compared with primary PDLSCs, the immortalized cells had a slower aging rate, maintained in a proliferative state without crisis for more than 30 passages, and retained the molecular markers and biological functions of primary ones. Using the PDLSC-Bmi1, we confirmed the promotive effect of naringin on osteogenesis. Naringin promoted the osteogenic differentiation of PDLSC-Bmi1 manifested as the increased activity of alkaline phosphatase (ALP), expression of the runt-related transcription factor 2 (Runx2) and osteocalcin (OCN), and formation of mineralized nodules. In addition, the extracellular regulated protein kinases (ERK) 1/2 was found to be activated by naringin, and the ERK1/2 specific inhibitor significantly inhibited naringin-induced osteogenic differentiation in PDLSC-Bmi1. Our results indicated that the overexpression of Bmi1 extended the life span of PDLSCs without perturbing their biological functions, and that naringin promoted the osteogenesis of PDLSC-Bmi1 at least partially through the ERK1/2 signaling pathway. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Short telomeres in hatchling snakes: erythrocyte telomere dynamics and longevity in tropical pythons.

PubMed

Ujvari, Beata; Madsen, Thomas

2009-10-16

Telomere length (TL) has been found to be associated with life span in birds and humans. However, other studies have demonstrated that TL does not affect survival among old humans. Furthermore, replicative senescence has been shown to be induced by changes in the protected status of the telomeres rather than the loss of TL. In the present study we explore whether age- and sex-specific telomere dynamics affect life span in a long-lived snake, the water python (Liasis fuscus). Erythrocyte TL was measured using the Telo TAGGG TL Assay Kit (Roche). In contrast to other vertebrates, TL of hatchling pythons was significantly shorter than that of older snakes. However, during their first year of life hatchling TL increased substantially. While TL of older snakes decreased with age, we did not observe any correlation between TL and age in cross-sectional sampling. In older snakes, female TL was longer than that of males. When using recapture as a proxy for survival, our results do not support that longer telomeres resulted in an increased water python survival/longevity. In fish high telomerase activity has been observed in somatic cells exhibiting high proliferation rates. Hatchling pythons show similar high somatic cell proliferation rates. Thus, the increase in TL of this group may have been caused by increased telomerase activity. In older humans female TL is longer than that of males. This has been suggested to be caused by high estrogen levels that stimulate increased telomerase activity. Thus, high estrogen levels may also have caused the longer telomeres in female pythons. The lack of correlation between TL and age among old snakes and the fact that longer telomeres did not appear to affect python survival do not support that erythrocyte telomere dynamics has a major impact on water python longevity.

Archaeal DNA replication.

PubMed

Kelman, Lori M; Kelman, Zvi

2014-01-01

DNA replication is essential for all life forms. Although the process is fundamentally conserved in the three domains of life, bioinformatic, biochemical, structural, and genetic studies have demonstrated that the process and the proteins involved in archaeal DNA replication are more similar to those in eukaryal DNA replication than in bacterial DNA replication, but have some archaeal-specific features. The archaeal replication system, however, is not monolithic, and there are some differences in the replication process between different species. In this review, the current knowledge of the mechanisms governing DNA replication in Archaea is summarized. The general features of the replication process as well as some of the differences are discussed.

Replication profile of Saccharomyces cerevisiae chromosome VI.

PubMed

Friedman, K L; Brewer, B J; Fangman, W L

1997-11-01

An understanding of the replication programme at the genome level will require the identification and characterization of origins of replication through large, contiguous regions of DNA. As a step toward this goal, origin efficiencies and replication times were determined for 10 ARSs spanning most of the 270 kilobase (kb) chromosome VI of Saccharomyces cerevisiae. Chromosome VI shows a wide variation in the percentage of cell cycles in which different replication origins are utilized. Most of the origins are activated in only a fraction of cells, suggesting that the pattern of origin usage on chromosome VI varies greatly within the cell population. The replication times of fragments containing chromosome VI origins show a temporal pattern that has been recognized on other chromosomes--the telomeres replicate late in S phase, while the central region of the chromosome replicates early. As demonstrated here for chromosome VI, analysis of the direction of replication fork movement along a chromosome and determination of replication time by measuring a period of hemimethylation may provide an efficient means of surveying origin activity over large regions of the genome.

Working memory and inhibitory control across the life span: Intrusion errors in the Reading Span Test.

PubMed

Robert, Christelle; Borella, Erika; Fagot, Delphine; Lecerf, Thierry; de Ribaupierre, Anik

2009-04-01

The aim of this study was to examine to what extent inhibitory control and working memory capacity are related across the life span. Intrusion errors committed by children and younger and older adults were investigated in two versions of the Reading Span Test. In Experiment 1, a mixed Reading Span Test with items of various list lengths was administered. Older adults and children recalled fewer correct words and produced more intrusions than did young adults. Also, age-related differences were found in the type of intrusions committed. In Experiment 2, an adaptive Reading Span Test was administered, in which the list length of items was adapted to each individual's working memory capacity. Age groups differed neither on correct recall nor on the rate of intrusions, but they differed on the type of intrusions. Altogether, these findings indicate that the availability of attentional resources influences the efficiency of inhibition across the life span.

Influence of resveratrol on oxidative stress resistance and life span in Caenorhabditis elegans.

PubMed

Chen, Wei; Rezaizadehnajafi, Leila; Wink, Michael

2013-05-01

Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol from red wine, has been reported to be beneficial in cases of ageing-related cardiovascular and neurodegenerative diseases owing to its property to reduce oxidative stress. Previous studies on the longevity promoting effect of resveratrol have been partly inconclusive, therefore we set out to investigate whether resveratrol at least promoted longevity in Caenorhabditis elegans under acute oxidative stress conditions. C. elegans was cultured under standard conditions with or without resveratrol. After exposure to juglone-induced acute oxidative stress, the survival rate and hsp-16.2::GFP expression were measured. The influence of resveratrol on life span was recorded also under oxidative stress induced by high glucose concentrations in the growth medium. No extension of the normal life span of C. elegans was observed either in liquid or solid growth media containing different concentrations of resveratrol. However, resveratrol alleviated juglone-induced lethal oxidative stress, and significantly prolonged the life span of C. elegans under conditions of acute oxidative damage and oxidative stress caused by high concentrations of glucose. Resveratrol, as an antioxidant, ameliorated oxidative stress in vivo but did not extend the life span of C. elegans under normal conditions. However, resveratrol did extend life span under conditions of oxidative stress. © 2013 The Authors. JPP © 2013 Royal Pharmaceutical Society.

Immortalization of Human Fetal Cells: The Life Span of Umbilical Cord Blood-derived Cells Can Be Prolonged without Manipulating p16INK4a/RB Braking PathwayD⃞

PubMed Central

Terai, Masanori; Uyama, Taro; Sugiki, Tadashi; Li, Xiao-Kang; Umezawa, Akihiro; Kiyono, Tohru

2005-01-01

Human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) are expected to serve as an excellent alternative to bone marrow-derived human mesenchymal stem cells. However, it is difficult to study them because of their limited life span. To overcome this problem, we attempted to produce a strain of UCBMSCs with a long life span and to investigate whether the strain could maintain phenotypes in vitro. UCBMSCs were infected with retrovirus carrying the human telomerase reverse transcriptase (hTERT) to prolong their life span. The UCBMSCs underwent 30 population doublings (PDs) and stopped dividing at PD 37. The UCBMSCs newly established with hTERT (UCBTERTs) proliferated for >120 PDs. The p16INK4a/RB braking pathway leading to senescence can be inhibited by introduction of Bmi-1, a polycomb-group gene, and human papillomavirus type 16 E7, but the extension of the life span of the UCBMSCs with hTERT did not require inhibition of the p16INK4a/RB pathway. The characteristics of the UCBTERTs remained unchanged during the prolongation of life span. UCBTERTs provide a powerful model for further study of cellular senescence and for future application to cell-based therapy by using umbilical cord blood cells. PMID:15647378

Sustained Attention Across the Life Span in a Sample of 10,000: Dissociating Ability and Strategy.

PubMed

Fortenbaugh, Francesca C; DeGutis, Joseph; Germine, Laura; Wilmer, Jeremy B; Grosso, Mallory; Russo, Kathryn; Esterman, Michael

2015-09-01

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 life span. In the present study, we filled this gap in two ways. First, using an unprecedentedly large 10,430-person sample, we modeled age-related differences with substantially greater precision than have prior efforts. Second, using the recently developed gradual-onset continuous performance test (gradCPT), we parsed sustained-attention performance over the life span into its ability and strategy components. We found that after the age of 15 years, the strategy and ability trajectories saliently diverge. Strategy becomes monotonically more conservative with age, whereas ability peaks in the early 40s and is followed by a gradual decline in older adults. These observed life-span trajectories for sustained attention are distinct from results of other life-span studies focusing on fluid and crystallized intelligence. © The Author(s) 2015.

Role of metabolic rate and DNA-repair in Drosophila aging Implications for the mitochondrial mutation theory of aging

NASA Technical Reports Server (NTRS)

Miquel, J.; Binnard, R.; Fleming, J. E.

1983-01-01

The notion that injury to mitochondrial DNA is a cause of intrinsic aging was tested by correlating the different respiration rates of several wild strains of Drosophila melanogaster with the life-spans. Respiration rate and aging in a mutant of D. melanogaster deficient in postreplication repair were also investigated. In agreement with the rate of living theory, there was an inverse relation between oxygen consumption and median life-span in flies having normal DNA repair. The mutant showed an abnormally low life-span as compared to the controls and also exhibited significant deficiency in mating fitness and a depressed metabolic rate. Therefore, the short life-span of the mutant may be due to the congenital condition rather than to accelerated aging.

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

PubMed

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.

Adaptive prolonged postreproductive life span in killer whales.

PubMed

Foster, Emma A; Franks, Daniel W; Mazzi, Sonia; Darden, Safi K; Balcomb, Ken C; Ford, John K B; Croft, Darren P

2012-09-14

Prolonged life after reproduction is difficult to explain evolutionarily unless it arises as a physiological side effect of increased longevity or it benefits related individuals (i.e., increases inclusive fitness). There is little evidence that postreproductive life spans are adaptive in nonhuman animals. By using multigenerational records for two killer whale (Orcinus orca) populations in which females can live for decades after their final parturition, we show that postreproductive mothers increase the survival of offspring, particularly their older male offspring. This finding may explain why female killer whales have evolved the longest postreproductive life span of all nonhuman animals.

Endosomal protein sorting and autophagy genes contribute to the regulation of yeast life span.

PubMed

Longo, Valter D; Nislow, Corey; Fabrizio, Paola

2010-11-01

Accumulating evidence from various organisms points to a role for autophagy in the regulation of life span. By performing a genome-wide screen to identify novel life span determinants in Saccharomyces cerevisiae, we have obtained further insights into the autophagy-related and -unrelated degradation processes that may be important for preventing cellular senescence. The generation of multivesicular bodies and their fusion with the vacuole in the endosomal pathway emerged as novel cell functions involved in yeast chronological survival and longevity extension.

Life and Self Meaning: The Process of Their Creation.

ERIC Educational Resources Information Center

Weenolsen, Patricia

Research has not addressed issues of life meaning in a life-span developmental framework. The Loss and Transcendence paradigm was developed as a humanistic-existential approach to life-span development which has as its central theme the concept that individuals are in a continuous process of creating their lives and their selves. To explore loss…

Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice.

PubMed

Strong, Randy; Miller, Richard A; Astle, Clinton M; Baur, Joseph A; de Cabo, Rafael; Fernandez, Elizabeth; Guo, Wen; Javors, Martin; Kirkland, James L; Nelson, James F; Sinclair, David A; Teter, Bruce; Williams, David; Zaveri, Nurulain; Nadon, Nancy L; Harrison, David E

2013-01-01

The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are hypothesized to increase life span and/or health span in genetically heterogeneous mice. Each compound is tested in parallel at three test sites. It is the goal of the ITP to publish all results, negative or positive. We report here on the results of lifelong treatment of mice, beginning at 4 months of age, with each of five agents, that is, green tea extract (GTE), curcumin, oxaloacetic acid, medium-chain triglyceride oil, and resveratrol, on the life span of genetically heterogeneous mice. Each agent was administered beginning at 4 months of age. None of these five agents had a statistically significant effect on life span of male or female mice, by log-rank test, at the concentrations tested, although a secondary analysis suggested that GTE might diminish the risk of midlife deaths in females only.

Evaluation of Resveratrol, Green Tea Extract, Curcumin, Oxaloacetic Acid, and Medium-Chain Triglyceride Oil on Life Span of Genetically Heterogeneous Mice

PubMed Central

Miller, Richard A.; Astle, Clinton M.; Baur, Joseph A.; de Cabo, Rafael; Fernandez, Elizabeth; Guo, Wen; Javors, Martin; Kirkland, James L.; Nelson, James F.; Sinclair, David A.; Teter, Bruce; Williams, David; Zaveri, Nurulain; Nadon, Nancy L.; Harrison, David E.

2013-01-01

The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are hypothesized to increase life span and/or health span in genetically heterogeneous mice. Each compound is tested in parallel at three test sites. It is the goal of the ITP to publish all results, negative or positive. We report here on the results of lifelong treatment of mice, beginning at 4 months of age, with each of five agents, that is, green tea extract (GTE), curcumin, oxaloacetic acid, medium-chain triglyceride oil, and resveratrol, on the life span of genetically heterogeneous mice. Each agent was administered beginning at 4 months of age. None of these five agents had a statistically significant effect on life span of male or female mice, by log-rank test, at the concentrations tested, although a secondary analysis suggested that GTE might diminish the risk of midlife deaths in females only. PMID:22451473

A Holistic Model for Wellness and Prevention over the Life Span.

ERIC Educational Resources Information Center

Witmer, J. Melvin; Sweeney, Thomas J.

1992-01-01

Presents integrated paradigm for wellness and prevention over the life span for purpose of theory building, research, clinical application, education, advocacy, and consciousness raising. Model described includes 11 characteristics desirable for optimal health and functioning. Notes characteristics are expressed through five life tasks of…

Explanatory style across the life span: evidence for stability over 52 years.

PubMed

Burns, M O; Seligman, M E

1989-03-01

Analyzed explanatory style across the life span. 30 Ss whose average age was 72 responded to questions about their current life and provided diaries or letters written in their youth, an average of 52 years earlier. A blind content analysis of explanatory style derived from these 2 sources revealed that explanatory style for negative events was stable throughout adult life (r = .54, p less than .002). In contrast, there appeared to be no stability of explanatory style for positive events between the same 2 time periods. These results suggest that explanatory style for negative events may persist across the life span and may constitute an enduring risk factor for depression, low achievement, and physical illness.

The Cost of Uncertain Life Span*

PubMed Central

Edwards, Ryan D.

2012-01-01

A considerable amount of uncertainty surrounds the length of human life. The standard deviation in adult life span is about 15 years in the U.S., and theory and evidence suggest it is costly. I calibrate a utility-theoretic model of preferences over length of life and show that one fewer year in standard deviation is worth about half a mean life year. Differences in the standard deviation exacerbate cross-sectional differences in life expectancy between the U.S. and other industrialized countries, between rich and poor countries, and among poor countries. Accounting for the cost of life-span variance also appears to amplify recently discovered patterns of convergence in world average human well-being. This is partly for methodological reasons and partly because unconditional variance in human length of life, primarily the component due to infant mortality, has exhibited even more convergence than life expectancy. PMID:22368324

ORC1/CDC6 and MCM7 distinct associate with chromatin through Trypanosoma cruzi life cycle.

PubMed

Calderano, Simone; Godoy, Patricia; Soares, Daiane; Sant'Anna, Osvaldo Augusto; Schenkman, Sergio; Elias, M Carolina

2014-02-01

Trypanosoma cruzi alternates between replicative and non-replicative stages. We analyzed the expression of components of the pre-replication machinery TcORC1/CDC6 and TcMCM7 and their interaction with DNA in all T. cruzi stages. TcORC1/CDC6 remains in the nuclear space during all stages of the life cycle and interacts with DNA in the replicative stages; however, it does not bind to DNA in the non-replicative forms. Moreover, TcMCM7 is not present in the non-replicative stages. These data suggest that the lacking of DNA replication during the T. cruzi life cycle may be a consequence of the blocking of TcORC1/CDC6-DNA interaction and of the down regulation of the TcMCM7 expression. Copyright © 2014 Elsevier B.V. All rights reserved.

SV40 T antigen alone drives karyotype instability that precedes neoplastic transformation of human diploid fibroblasts.

PubMed

Ray, F A; Peabody, D S; Cooper, J L; Cram, L S; Kraemer, P M

1990-01-01

To define the role of SV40 large T antigen in the transformation and immortalization of human cells, we have constructed a plasmid lacking most of the unique coding sequences of small t antigen as well as the SV40 origin of replication. The promoter for T antigen, which lies within the origin of replication, was deleted and replaced by the Rous sarcoma virus promoter. This minimal construct was co-electroporated into normal human fibroblasts of neonatal origin along with a plasmid containing the neomycin resistance gene (neo). Three G418-resistant, T antigen-positive clones were expanded and compared to three T antigen-positive clones that received the pSV3neo plasmid (capable of expressing large and small T proteins and having two origins of replication). Autonomous replication of plasmid DNA was observed in all three clones that received pSV3neo but not in any of the three origin minus clones. Immediately after clonal expansion, several parameters of neoplastic transformation were assayed. Low percentages of cells in T antigen-positive populations were anchorage independent or capable of forming colonies in 1% fetal bovine serum. The T antigen-positive clones generally exhibited an extended lifespan in culture but rarely became immortalized. Large numbers of dead cells were continually generated in all T antigen-positive, pre-crisis populations. Ninety-nine percent of all T antigen-positive cells had numerical or structural chromosome aberrations. Control cells that received the neo gene did not have an extended life span, did not have noticeable numbers of dead cells, and did not exhibit karyotype instability. We suggest that the role of T antigen protein in the transformation process is to generate genetic hypervariability, leading to various consequences including neoplastic transformation and cell death.

[Genome loses all 5-methylcytosine a life span. How is this connected with accumulation of mutations during aging?].

PubMed

Mazin, A L

1993-01-01

The 5-methylcytosine (5mC) content in liver DNA has been determined for rats of different age. The rate of the 5mC loss from DNA is maximal in pre- and neonatal rats, 1.28% of reduction of the 5mC content per day, then it decreases to 0.33% and becomes minimal and constant in adult rats, 0.028% per day. During pregnancy and the first 15 days of postnatal development rat genome loses 49% of all 5mC. Within the next 45 days 15% of 5mC disappears, and during maximal rat life span, about four years, 39% of the genomic 5mC may be lost. Thus, it has been found for the first time that the animal genome loses practically all 5mC residues during the life span. Analysis of the literature data shows that for embryos the rate of the 5mC loss from DNA proves to be higher than that for adult animals by 96 times for mice, 69-for rats and 28-for cows. The rate of embryonal DNA hypomethylation may be inversely proportional to the pregnancy duration of species. In adult animals the rate inversely correlates with their maximal life span and accounts for the 5mC loss from DNA of a mouse by 0.028%, of a rat by 0.024%, of a hamster by 0.007%, of a cow by 0.004% and of a human being by 0.0005% per day. During the entire ontogenesis, the genome of a mouse loses 93% of all 5mC residues, that of a rat-101% and of a cow-88%. The age-dependent loss of 5mC from DNA is also typical for cell lines aging in vitro. It is constant, as a rule, and correlates with the number of cell population doublings (PD). The removal of all 5mC from DNA corresponds to 70-130 PD for human, 40-60 PD-for hamster and 6 PD- for mouse cells. In immortal lines the level of DNA methylation is stable or grows with age. A possible mechanism of an age-related 5mC loss from DNA is discussed. DNA hypomethylation may result from 5mC deamination directly at the moment of replicative DNA methylation and subsequent reparation of the G.T mispairs which leads to accumulation of the 5mC-->T+C substitutions in the genome with each cell division. So DNA methylation may serve as an ideal mechanism for counting cell divisions in vivo and in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)

Life-Span Developmental Psychology: Non-Normative Life Events. A Review of the Seventh West Virginia University Life-Span Developmental Psychology Conference.

ERIC Educational Resources Information Center

Richardson, Gale A.; Kwiatkowski, Bonnie M.

1981-01-01

Topics covered in this conference included parenting, terminal illness, the birth of severely disabled children, rape and family violence, separation and divorce, and hospitalization, and dealt with a wide range of methodologies and age periods. (Author/RH)

Sex differences in life span: Females homozygous for the X chromosome do not suffer the shorter life span predicted by the unguarded X hypothesis.

PubMed

Brengdahl, Martin; Kimber, Christopher M; Maguire-Baxter, Jack; Friberg, Urban

2018-03-01

Life span differs between the sexes in many species. Three hypotheses to explain this interesting pattern have been proposed, involving different drivers: sexual selection, asymmetrical inheritance of cytoplasmic genomes, and hemizygosity of the X(Z) chromosome (the unguarded X hypothesis). Of these, the unguarded X has received the least experimental attention. This hypothesis suggests that the heterogametic sex suffers a shortened life span because recessive deleterious alleles on its single X(Z) chromosome are expressed unconditionally. In Drosophila melanogaster, the X chromosome is unusually large (∼20% of the genome), providing a powerful model for evaluating theories involving the X. Here, we test the unguarded X hypothesis by forcing D. melanogaster females from a laboratory population to express recessive X-linked alleles to the same degree as males, using females exclusively made homozygous for the X chromosome. We find no evidence for reduced life span or egg-to-adult viability due to X homozygozity. In contrast, males and females homozygous for an autosome both suffer similar, significant reductions in those traits. The logic of the unguarded X hypothesis is indisputable, but our results suggest that the degree to which recessive deleterious X-linked alleles depress performance in the heterogametic sex appears too small to explain general sex differences in life span. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

The Impact of Life Stages on Parent-Child Relationships: A Comparative Look at Japanese & American University Students

ERIC Educational Resources Information Center

Takei, Yoshimitsu; Honda, Tokio; Shieh, Sheau-Hue

2007-01-01

Adolescence is often considered a period in a person's life when important physiological and emotional changes occur. When discussing adolescence, however, it should not be forgotten that it is just another stage in one's life span between birth and death. By adopting a life-span perspective, researchers are more likely to consider contextual…

Stable long-term cultures of self-renewing B cells and their applications.

PubMed

Kwakkenbos, Mark J; van Helden, Pauline M; Beaumont, Tim; Spits, Hergen

2016-03-01

Monoclonal antibodies are essential therapeutics and diagnostics in a large number of diseases. Moreover, they are essential tools in all sectors of life sciences. Although the great majority of monoclonal antibodies currently in use are of mouse origin, the use of human B cells to generate monoclonal antibodies is increasing as new techniques to tap the human B cell repertoire are rapidly emerging. Cloned lines of immortalized human B cells are ideal sources of monoclonal antibodies. In this review, we summarize our studies to the regulation of the replicative life span, differentiation, and maturation of B cells that led to the development of a platform that uses immortalization of human B cells by in vitro genetic modification for antibody development. We describe a number of human antibodies that were isolated using this platform and the application of the technique in other species. We also discuss the use of immortalized B cells as antigen-presenting cells for the discovery of tumor neoantigens. © 2016 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

Self Organization in Compensated Semiconductors

NASA Astrophysics Data System (ADS)

Berezin, Alexander A.

2004-03-01

In partially compensated semiconductor (PCS) Fermi level is pinned to donor sub-band. Due to positional randomness and almost isoenergetic hoppings, donor-spanned electronic subsystem in PCS forms fluid-like highly mobile collective state. This makes PCS playground for pattern formation, self-organization, complexity emergence, electronic neural networks, and perhaps even for origins of life, bioevolution and consciousness. Through effects of impact and/or Auger ionization of donor sites, whole PCS may collapse (spinodal decomposition) into microblocks potentially capable of replication and protobiological activity (DNA analogue). Electronic screening effects may act in RNA fashion by introducing additional length scale(s) to system. Spontaneous quantum computing on charged/neutral sites becomes potential generator of informationally loaded microstructures akin to "Carl Sagan Effect" (hidden messages in Pi in his "Contact") or informational self-organization of "Library of Babel" of J.L. Borges. Even general relativity effects at Planck scale (R.Penrose) may affect the dynamics through (e.g.) isotopic variations of atomic mass and local density (A.A.Berezin, 1992). Thus, PCS can serve as toy model (experimental and computational) at interface of physics and life sciences.

Revision of XLM-2013-1129 as invited by the Action Editor, Rebekah Smith

PubMed Central

Naveh-Benjamin, Moshe; Kilb, Angela; Maddox, Geoff; Thomas, Jenna; Fine, Hope; Chen, Tina; Cowan, Nelson

2014-01-01

Although older adults have lower working memory spans on average than young adults, we demonstrate in five experiments one way in which older adults paradoxically resemble higher-capacity young adults. Specifically, in a selective-listening task, older adults almost always failed to notice their names presented in an unattended channel. This is an exaggeration of what high-span young adults show, and the opposite of what low spans show. This striking finding in older adults remained significant after controlling for working memory span and for noticing their names in an attended channel. The findings were replicated when presentation rate was made slower and when the ear in which the unattended name was presented was controlled. These results point to an account of older adults’ performance involving not only an inhibition factor, which allows high-span young adults to suppress the channel to be ignored, but also an attentional capacity factor, with more unallocated capacity allowing low-span young adults to notice their names much more often than older adults with comparably low spans. PMID:24820668

Identity, prudential concern, and extended lives.

PubMed

Glannon, Walter

2002-06-01

Recent advances in human genetics suggest that it may become possible to genetically manipulate telomerase and embryonic stem cells to alter the mechanisms of aging and extend the human life span. But a life span significantly longer than the present norm would be undesirable because it would severely weaken the connections between past- and future-oriented mental states and turn the psychological grounds for personal identity and prudential concern for our future selves. In addition, the collective effects of longer lives might lower the quality of life for all people. These two problems provide reasons against genetic manipulation of cells to alter the length of the human life span.

Phosphorylation of CMG helicase and Tof1 is required for programmed fork arrest

PubMed Central

Bastia, Deepak; Srivastava, Pankaj; Zaman, Shamsu; Choudhury, Malay; Mohanty, Bidyut K.; Bacal, Julien; Langston, Lance D.; Pasero, Philippe; O’Donnell, Michael E.

2016-01-01

Several important physiological transactions, including control of replicative life span (RLS), prevention of collision between replication and transcription, and cellular differentiation, require programmed replication fork arrest (PFA). However, a general mechanism of PFA has remained elusive. We previously showed that the Tof1–Csm3 fork protection complex is essential for PFA by antagonizing the Rrm3 helicase that displaces nonhistone protein barriers that impede fork progression. Here we show that mutations of Dbf4-dependent kinase (DDK) of Saccharomyces cerevisiae, but not other DNA replication factors, greatly reduced PFA at replication fork barriers in the spacer regions of the ribosomal DNA array. A key target of DDK is the mini chromosome maintenance (Mcm) 2–7 complex, which is known to require phosphorylation by DDK to form an active CMG [Cdc45 (cell division cycle gene 45), Mcm2–7, GINS (Go, Ichi, Ni, and San)] helicase. In vivo experiments showed that mutational inactivation of DDK caused release of Tof1 from the chromatin fractions. In vitro binding experiments confirmed that CMG and/or Mcm2–7 had to be phosphorylated for binding to phospho-Tof1–Csm3 but not to its dephosphorylated form. Suppressor mutations that bypass the requirement for Mcm2–7 phosphorylation by DDK restored PFA in the absence of the kinase. Retention of Tof1 in the chromatin fraction and PFA in vivo was promoted by the suppressor mcm5-bob1, which bypassed DDK requirement, indicating that under this condition a kinase other than DDK catalyzed the phosphorylation of Tof1. We propose that phosphorylation regulates the recruitment and retention of Tof1–Csm3 by the replisome and that this complex antagonizes the Rrm3 helicase, thereby promoting PFA, by preserving the integrity of the Fob1–Ter complex. PMID:27298353

Life-Span Extension in Mice by Preweaning Food Restriction and by Methionine Restriction in Middle Age

PubMed Central

Sun, Liou; Sadighi Akha, Amir A.; Miller, Richard A.

2009-01-01

Life span can be extended in rodents by restricting food availability (caloric restriction [CR]) or by providing food low in methionine (Meth-R). Here, we show that a period of food restriction limited to the first 20 days of life, via a 50% enlargement of litter size, shows extended median and maximal life span relative to mice from normal sized litters and that a Meth-R diet initiated at 12 months of age also significantly increases longevity. Furthermore, mice exposed to a CR diet show changes in liver messenger RNA patterns, in phosphorylation of Erk, Jnk2, and p38 kinases, and in phosphorylation of mammalian target of rapamycin and its substrate 4EBP1, HE-binding protein 1 that are not observed in liver from age-matched Meth-R mice. These results introduce new protocols that can increase maximal life span and suggest that the spectrum of metabolic changes induced by low-calorie and low-methionine diets may differ in instructive ways. PMID:19414512

The Writing Process: Effects of Life-Span Development on Imaging.

ERIC Educational Resources Information Center

Shock, Diane Hahn

A qualitative study focused on incubation and illumination within the act of writing to determine if life-span development affects image production during these creative, cognitive acts. Sixteen subjects of both sexes from four age groups represented major developmental stages in the life cycle. The research design provided two 90-minute sessions…

Personal Goals and Well-Being: How Do Young People Navigate Their Lives?

ERIC Educational Resources Information Center

Salmela-Aro, Katariina

2010-01-01

This chapter examines development through different life transitions, such as educational transitions and transition to parenthood during adolescence to adulthood in the context of the life-span model of personal goals. According to the life-span model of motivation, four key mechanisms--channeling, choice, co-regulation, and compensation--play a…

A CRTCal link between energy and life span.

PubMed

Brunet, Anne

2011-04-06

Cutting down calories prolongs life, but how this works remains largely unknown. A recent study in Nature (Mair et al., 2011) shows that life span extension triggered by the energy-sensing protein kinase AMPK is mediated by an evolutionarily conserved transcriptional circuit involving CRTC-1 and CREB. Copyright © 2011 Elsevier Inc. All rights reserved.

Visual Search Across the Life Span

ERIC Educational Resources Information Center

Hommel, Bernhard; Li, Karen Z. H.; Li, Shu-Chen

2004-01-01

Gains and losses in visual search were studied across the life span in a representative sample of 298 individuals from 6 to 89 years of age. Participants searched for single-feature and conjunction targets of high or low eccentricity. Search was substantially slowed early and late in life, age gradients were more pronounced in conjunction than in…

Improvement/Maintenance and Reorientation as Central Features of Coping with Major Life Change and Loss: Contributions of Three Life-Span Theories

ERIC Educational Resources Information Center

Boerner, Kathrin; Jopp, Daniela

2007-01-01

This article focuses on the common and unique contributions of three major life-span theories in addressing improvement/maintenance and reorientation, which represent central processes of coping with major life change and loss. For this purpose, we review and compare the dual-process model of assimilative and accommodative coping, the model of…

Lack of evolvability in self-sustaining autocatalytic networks constraints metabolism-first scenarios for the origin of life.

PubMed

Vasas, Vera; Szathmáry, Eörs; Santos, Mauro

2010-01-26

A basic property of life is its capacity to experience Darwinian evolution. The replicator concept is at the core of genetics-first theories of the origin of life, which suggest that self-replicating oligonucleotides or their similar ancestors may have been the first "living" systems and may have led to the evolution of an RNA world. But problems with the nonenzymatic synthesis of biopolymers and the origin of template replication have spurred the alternative metabolism-first scenario, where self-reproducing and evolving proto-metabolic networks are assumed to have predated self-replicating genes. Recent theoretical work shows that "compositional genomes" (i.e., the counts of different molecular species in an assembly) are able to propagate compositional information and can provide a setup on which natural selection acts. Accordingly, if we stick to the notion of replicator as an entity that passes on its structure largely intact in successive replications, those macromolecular aggregates could be dubbed "ensemble replicators" (composomes) and quite different from the more familiar genes and memes. In sharp contrast with template-dependent replication dynamics, we demonstrate here that replication of compositional information is so inaccurate that fitter compositional genomes cannot be maintained by selection and, therefore, the system lacks evolvability (i.e., it cannot substantially depart from the asymptotic steady-state solution already built-in in the dynamical equations). We conclude that this fundamental limitation of ensemble replicators cautions against metabolism-first theories of the origin of life, although ancient metabolic systems could have provided a stable habitat within which polymer replicators later evolved.

The Theory of Relativity: A Metatheory for Development?

ERIC Educational Resources Information Center

Sinnott, Jan Dynda

1981-01-01

Reviews relativity theory in physics to derive a relativistic metatheory applicable to life span developmental psychology. The discussion points out ways in which relativistic thinking might enhance understanding of life span development and epistemology. (Author/DB)

The primacy of primary control is a human universal: a reply to Gould's (1999) critique of the life-span theory of control.

PubMed

Heckhausen, J; Schulz, R

1999-07-01

This reply to S. J. Gould's (1999) critique of J. Heckhausen and R. Schulz's (1995) life-span theory of control addresses four issues: (1) the universal claim that primary control holds functional primacy over secondary control, (2) the status of secondary control as a confederate to primary control, (3) empirical evidence and paradigms for investigating universality and cultural variations, and (4) the capacity of the human control system to manage both gains and losses in control throughout the life span and aging-related decline in particular. Theoretical perspectives and empirical evidence from evolutionary, comparative, developmental, and cultural psychology are presented to support the authors' view that primary control striving holds functional primacy throughout the life span and across cultural and historical settings. Recommendations for empirically investigating the variations in the way primary control striving is expressed in different cultures are outlined.

Reproductive adaptation in Drosophila exposed to oxygen-enriched atmospheres

NASA Technical Reports Server (NTRS)

Kloek, G.; Winkle, L.

1979-01-01

Ten successive generations of a Drosophila melanogaster population were exposed to an atmospheric mix of 50% oxygen/50% nitrogen at standard pressure. This atmospheric mix has been shown to be toxic to this species and causes significantly shortened life span. By the fifth generation, survivorship and life span for the first 25-30 days were identical to control populations and total life span was shorter by only a few days. Egg-laying rates were stable in the experimental populations but below those of the controls. Hatching success was identical between experimental and control populations. Even though the egg-laying rates were lower in 50% oxygen, it was concluded that the population had adapted and could maintain a stable population in these conditions. The near-normal life spans, normal hatching rates, and overall population stability, exhibited following five generations of adaptation, were considered sufficient to allow continued reproduction in spite of a reduced egg-laying rate.

Life-span extension by a metacaspase in the yeast Saccharomyces cerevisiae.

PubMed

Hill, Sandra Malmgren; Hao, Xinxin; Liu, Beidong; Nyström, Thomas

2014-06-20

Single-cell species harbor ancestral structural homologs of caspase proteases, although the evolutionary benefit of such apoptosis-related proteins in unicellular organisms is unclear. Here, we found that the yeast metacaspase Mca1 is recruited to the insoluble protein deposit (IPOD) and juxtanuclear quality-control compartment (JUNQ) during aging and proteostatic stress. Elevating MCA1 expression counteracted accumulation of unfolded proteins and aggregates and extended life span in a heat shock protein Hsp104 disaggregase- and proteasome-dependent manner. Consistent with a role in protein quality control, genetic interaction analysis revealed that MCA1 buffers against deficiencies in the Hsp40 chaperone YDJ1 in a caspase cysteine-dependent manner. Life-span extension and aggregate management by Mca1 was only partly dependent on its conserved catalytic cysteine, which suggests that Mca1 harbors both caspase-dependent and independent functions related to life-span control. Copyright © 2014, American Association for the Advancement of Science.

Reproductive adaptation in Drosophila exposed to oxygen-enriched atmospheres.

PubMed

Kloek, G; Winkle, L

1979-04-01

Ten successive generations of a Drosophila melanogaster population were exposed to an atmospheric mix of 50% oxygen/50% nitrogen at standard pressure. This atmospheric mix has been shown to be toxic to this species and causes significantly shortened life span. By the fifth generation, survivorship and life span for the first 25-30 days were identical to control populations and total life span was shorter by only a few days. Egg-laying rates were stable in the experimental populations but below those of the controls. Hatching success was identical between experimental and control populations. Even though the egg-laying rates were lower in 50% oxygen, it was concluded that the population had adapted and could maintain a stable population in these conditions. The near-normal life spans, normal hatching rates, and overall population stability, exhibited following five generations of adaptation, were considered sufficient to allow continued reproduction in spite of a reduced egg-laying rate.

Does Dietary Restriction Reduce Life Span in Male Fruit-feeding Butterflies?

PubMed Central

Molleman, Freerk; Ding, Jimin; Boggs, Carol L.; Carey, James R.; Arlet, Małgorzata E.

2009-01-01

Male life history and resource allocation is not frequently studied in aging and life span research. Here we verify that males of long-lived fruit-feeding butterfly species have reduced longevity on restricted diets (Beck 2007 Oecologia), in contrast to the common finding of longevity extension in dietary restriction experiments in Drosophila and some other organisms. Males of some of the most long-lived species of fruit-feeding butterflies were collected from Kibale Forest, Uganda, and kept on diets of either sugar or mashed banana. Seven out of eight species had non-significantly longer life spans on mashed banana diets. Data analysis using a time-varying Cox-model with species as covariate showed that males had reduced survival on the sugar diet during the first 35 days of captive life, but the effect was absent or reversed at more advanced ages. These results challenge the generality of dietary restriction as a way to extend life span in animals. We argue that such studies on males are promising tools for better understanding life history evolution and aging because males display a wider variety of tactics for obtaining reproductive success than females. PMID:19580860

Nutritional Control of Chronological Aging and Heterochromatin in Saccharomyces cerevisiae.

PubMed

McCleary, David F; Rine, Jasper

2017-03-01

Calorie restriction extends life span in organisms as diverse as yeast and mammals through incompletely understood mechanisms.The role of NAD + -dependent deacetylases known as Sirtuins in this process, particularly in the yeast Saccharomyces cerevisiae , is controversial. We measured chronological life span of wild-type and sir2 Δ strains over a higher glucose range than typically used for studying yeast calorie restriction. sir2 Δ extended life span in high glucose complete minimal medium and had little effect in low glucose medium, revealing a partial role for Sir2 in the calorie-restriction response under these conditions. Experiments performed on cells grown in rich medium with a newly developed genetic strategy revealed that sir2 Δ shortened life span in low glucose while having little effect in high glucose, again revealing a partial role for Sir2 In complete minimal media, Sir2 shortened life span as glucose levels increased; whereas in rich media, Sir2 extended life span as glucose levels decreased. Using a genetic strategy to measure the strength of gene silencing at HML , we determined increasing glucose stabilized Sir2-based silencing during growth on complete minimal media. Conversely, increasing glucose destabilized Sir-based silencing during growth on rich media, specifically during late cell divisions. In rich medium, silencing was far less stable in high glucose than in low glucose during stationary phase. Therefore, Sir2 was involved in a response to nutrient cues including glucose that regulates chronological aging, possibly through Sir2-dependent modification of chromatin or deacetylation of a nonhistone protein. Copyright © 2017 by the Genetics Society of America.

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

PubMed

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

2009-12-01

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

Replication of alpha-satellite DNA arrays in endogenous human centromeric regions and in human artificial chromosome

PubMed Central

Erliandri, Indri; Fu, Haiqing; Nakano, Megumi; Kim, Jung-Hyun; Miga, Karen H.; Liskovykh, Mikhail; Earnshaw, William C.; Masumoto, Hiroshi; Kouprina, Natalay; Aladjem, Mirit I.; Larionov, Vladimir

2014-01-01

In human chromosomes, centromeric regions comprise megabase-size arrays of 171 bp alpha-satellite DNA monomers. The large distances spanned by these arrays preclude their replication from external sites and imply that the repetitive monomers contain replication origins. However, replication within these arrays has not previously been profiled and the role of alpha-satellite DNA in initiation of DNA replication has not yet been demonstrated. Here, replication of alpha-satellite DNA in endogenous human centromeric regions and in de novo formed Human Artificial Chromosome (HAC) was analyzed. We showed that alpha-satellite monomers could function as origins of DNA replication and that replication of alphoid arrays organized into centrochromatin occurred earlier than those organized into heterochromatin. The distribution of inter-origin distances within centromeric alphoid arrays was comparable to the distribution of inter-origin distances on randomly selected non-centromeric chromosomal regions. Depletion of CENP-B, a kinetochore protein that binds directly to a 17 bp CENP-B box motif common to alpha-satellite DNA, resulted in enrichment of alpha-satellite sequences for proteins of the ORC complex, suggesting that CENP-B may have a role in regulating the replication of centromeric regions. Mapping of replication initiation sites in the HAC revealed that replication preferentially initiated in transcriptionally active regions. PMID:25228468

Relationships of leaf dark respiration to leaf nitrogen, specific leaf area and leaf life-span: a test across biomes and functional groups.

PubMed

Reich, Peter B; Walters, Michael B; Ellsworth, David S; Vose, James M; Volin, John C; Gresham, Charles; Bowman, William D

1998-05-01

Based on prior evidence of coordinated multiple leaf trait scaling, we hypothesized that variation among species in leaf dark respiration rate (R d ) should scale with variation in traits such as leaf nitrogen (N), leaf life-span, specific leaf area (SLA), and net photosynthetic capacity (A max ). However, it is not known whether such scaling, if it exists, is similar among disparate biomes and plant functional types. We tested this idea by examining the interspecific relationships between R d measured at a standard temperature and leaf life-span, N, SLA and A max for 69 species from four functional groups (forbs, broad-leafed trees and shrubs, and needle-leafed conifers) in six biomes traversing the Americas: alpine tundra/subalpine forest, Colorado; cold temperate forest/grassland, Wisconsin; cool temperate forest, North Carolina; desert/shrubland, New Mexico; subtropical forest, South Carolina; and tropical rain forest, Amazonas, Venezuela. Area-based R d was positively related to area-based leaf N within functional groups and for all species pooled, but not when comparing among species within any site. At all sites, mass-based R d (R d-mass ) decreased sharply with increasing leaf life-span and was positively related to SLA and mass-based A max and leaf N (leaf N mass ). These intra-biome relationships were similar in shape and slope among sites, where in each case we compared species belonging to different plant functional groups. Significant R d-mass -N mass relationships were observed in all functional groups (pooled across sites), but the relationships differed, with higher R d at any given leaf N in functional groups (such as forbs) with higher SLA and shorter leaf life-span. Regardless of biome or functional group, R d-mass was well predicted by all combinations of leaf life-span, N mass and/or SLA (r 2 ≥ 0.79, P < 0.0001). At any given SLA, R d-mass rises with increasing N mass and/or decreasing leaf life-span; and at any level of N mass , R d-mass rises with increasing SLA and/or decreasing leaf life-span. The relationships between R d and leaf traits observed in this study support the idea of a global set of predictable interrelationships between key leaf morphological, chemical and metabolic traits.

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

PubMed

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.

Antioxidants, metabolic rate and aging in Drosophila

NASA Technical Reports Server (NTRS)

Miquel, J.; Fleming, J.; Economos, A. C.

1982-01-01

The metabolic rate-of-living theory of aging was investigated by determining the effect of several life-prolonging antioxidants on the metabolic rate and life span of Drosophila. The respiration rate of groups of continuously agitated flies was determined in a Gilson respirometer. Vitamin E, 2,4-dinitrophenol, nordihydroguaiaretic acid, and thiazolidine carboxylic acid were employed as antioxidants. Results show that all of these antioxidants reduced the oxygen consumption rate and increased the mean life span, and a significant negative linear correlation was found between the mean life span and the metabolic rate. It is concluded that these findings indicate that some antioxidants may inhibit respiration rate in addition to their protective effect against free radical-induced cellular damage.

Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans.

PubMed

Park, Sang-Kyu; Link, Christopher D; Johnson, Thomas E

2010-02-01

Recent studies have shown that the rate of aging can be modulated by diverse interventions. Dietary restriction is the most widely used intervention to promote longevity; however, the mechanisms underlying the effect of dietary restriction remain elusive. In a previous study, we identified two novel genes, nlp-7 and cup-4, required for normal longevity in Caenorhabditis elegans. nlp-7 is one of a set of neuropeptide-like protein genes; cup-4 encodes an ion-channel involved in endocytosis by coelomocytes. Here, we assess whether nlp-7 and cup-4 mediate longevity increases by dietary restriction. RNAi of nlp-7 or cup-4 significantly reduces the life span of the eat-2 mutant, a genetic model of dietary restriction, but has no effect on the life span of long-lived mutants resulting from reduced insulin/IGF-1 signaling or dysfunction of the mitochondrial electron transport chain. The life-span extension observed in wild-type N2 worms by dietary restriction using bacterial dilution is prevented significantly in nlp-7 and cup-4 mutants. RNAi knockdown of genes encoding candidate receptors of NLP-7 and genes involved in endocytosis by coelomocytes also specifically shorten the life span of the eat-2 mutant. We conclude that two novel pathways, NLP-7 signaling and endocytosis by coelomocytes, are required for life extension under dietary restriction in C. elegans.

The control processes and subjective well-being of Chinese teachers: evidence of convergence with and divergence from the key propositions of the motivational theory of life-span development

PubMed Central

Wong, Wan-chi; Li, Yin; Sun, Xiaoyan; Xu, Huanu

2014-01-01

An analytical review of the motivational theory of life-span development reveals that this theory has undergone a series of elegant theoretical integrations. Its claim to universality nonetheless brings forth unresolved controversies. With the purpose of scrutinizing the key propositions of this theory, an empirical study was designed to examine the control processes and subjective well-being of Chinese teachers (N = 637). The OPS-Scales (Optimization in Primary and Secondary Control Scales) for the Domain of Teaching were constructed to assess patterns of control processes. Three facets of subjective well-being were investigated with the Positive and Negative Affect Schedule, the Life Satisfaction Scale, and the Subjective Vitality Scale. The results revealed certain aspects of alignment with and certain divergences from the key propositions of the motivational theory of life-span development. Neither “primacy of primary control” nor “primacy of secondary control” was clearly supported. Notably, using different criteria for subjective well-being yielded different subtypes of primary and secondary control as predictors. The hypothesized life-span trajectories of primary and secondary control received limited support. To advance the theory in this area, we recommend incorporating Lakatos' ideas about sophisticated falsification by specifying the hard core of the motivational theory of life-span development and articulating new auxiliary hypotheses. PMID:24904483

Foraging across the life span: is there a reduction in exploration with aging?

PubMed Central

Mata, Rui; Wilke, Andreas; Czienskowski, Uwe

2013-01-01

Does foraging change across the life span, and in particular, with aging? We report data from two foraging tasks used to investigate age differences in search in external environments as well as internal search in memory. Overall, the evidence suggests that foraging behavior may undergo significant changes across the life span across internal and external search. In particular, we find evidence of a trend toward reduced exploration with increased age. We discuss these findings in light of theories that postulate a link between aging and reductions in novelty seeking and exploratory behavior. PMID:23616741

Detection of density dependence requires density manipulations and calculation of lambda.

PubMed

Fowler, N L; Overath, R Deborah; Pease, Craig M

2006-03-01

To investigate density-dependent population regulation in the perennial bunchgrass Bouteloua rigidiseta, we experimentally manipulated density by removing adults or adding seeds to replicate quadrats in a natural population for three annual intervals. We monitored the adjacent control quadrats for 14 annual intervals. We constructed a population projection matrix for each quadrat in each interval, calculated lambda, and did a life table response experiment (LTRE) analysis. We tested the effects of density upon lambda by comparing experimental and control quadrats, and by an analysis of the 15-year observational data set. As measured by effects on lambda and on N(t+1/Nt in the experimental treatments, negative density dependence was strong: the population was being effectively regulated. The relative contributions of different matrix elements to treatment effect on lambda differed among years and treatments; overall the pattern was one of small contributions by many different life cycle stages. In contrast, density dependence could not be detected using only the observational (control quadrats) data, even though this data set covered a much longer time span. Nor did experimental effects on separate matrix elements reach statistical significance. These results suggest that ecologists may fail to detect density dependence when it is present if they have only descriptive, not experimental, data, do not have data for the entire life cycle, or analyze life cycle components separately.

Life as a cosmic imperative?

PubMed

de Duve, Christian

2011-02-13

The origin of life on Earth may be divided into two stages separated by the first appearance of replicable molecules, most probably of RNA. The first stage depended exclusively on chemistry. The second stage likewise involved chemistry, but with the additional participation of selection, a necessary concomitant of inevitable replication accidents. Consideration of these two processes suggests that the origin of life may have been close to obligatory under the physical-chemical conditions that prevailed at the site of its birth. Thus, an extrasolar planet in which those conditions were replicated appears as a probable site for the appearance of extra-terrestrial life.

Life Origination and Development Hydrate theory (LOH-Theory): new approaches to the problems of the optimal nutrition and life prolongation

NASA Astrophysics Data System (ADS)

Kadyshevich, E. A.; Ostrovskii, V. E.

2014-04-01

Life Origination Hydrate Theory (LOH-Theory) and Mitosis and Replication Hydrate Theory (MRHTheory), both grounded on the notion of honeycomb gas-hydrate structures formation/destruction as the physicochemical phenomenon governing the DNA origination and replication, allow new approaches to the optimal nutrition and life prolongation problems.

Oxidative stress and the evolution of sex differences in life span and ageing in the decorated cricket, Gryllodes sigillatus.

PubMed

Archer, Catharine R; Sakaluk, Scott K; Selman, Colin; Royle, Nick J; Hunt, John

2013-03-01

The Free Radical Theory of Ageing (FRTA) predicts that oxidative stress, induced when levels of reactive oxygen species exceed the capacity of antioxidant defenses, causes ageing. Recently, it has also been argued that oxidative damage may mediate important life-history trade-offs. Here, we use inbred lines of the decorated cricket, Gryllodes sigillatus, to estimate the genetic (co)variance between age-dependent reproductive effort, life span, ageing, oxidative damage, and total antioxidant capacity within and between the sexes. The FRTA predicts that oxidative damage should accumulate with age and negatively correlate with life span. We find that protein oxidation is greater in the shorter lived sex (females) and negatively genetically correlated with life span in both sexes. However, oxidative damage did not accumulate with age in either sex. Previously we have shown antagonistic pleiotropy between the genes for early-life reproductive effort and ageing rate in both sexes, although this was stronger in females. In females, we find that elevated fecundity early in life is associated with greater protein oxidation later in life, which is in turn positively correlated with the rate of ageing. Our results provide mixed support for the FRTA but suggest that oxidative stress may mediate sex-specific life-history strategies in G. sigillatus. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Functional RNA elements in the dengue virus genome.

PubMed

Gebhard, Leopoldo G; Filomatori, Claudia V; Gamarnik, Andrea V

2011-09-01

Dengue virus (DENV) genome amplification is a process that involves the viral RNA, cellular and viral proteins, and a complex architecture of cellular membranes. The viral RNA is not a passive template during this process; it plays an active role providing RNA signals that act as promoters, enhancers and/or silencers of the replication process. RNA elements that modulate RNA replication were found at the 5' and 3' UTRs and within the viral coding sequence. The promoter for DENV RNA synthesis is a large stem loop structure located at the 5' end of the genome. This structure specifically interacts with the viral polymerase NS5 and promotes RNA synthesis at the 3' end of a circularized genome. The circular conformation of the viral genome is mediated by long range RNA-RNA interactions that span thousands of nucleotides. Recent studies have provided new information about the requirement of alternative, mutually exclusive, structures in the viral RNA, highlighting the idea that the viral genome is flexible and exists in different conformations. In this article, we describe elements in the promoter SLA and other RNA signals involved in NS5 polymerase binding and activity, and provide new ideas of how dynamic secondary and tertiary structures of the viral RNA participate in the viral life cycle.

Corrigendum: Childhood Adversity, Self-Esteem, and Diurnal Cortisol Profiles Across the Life Span.

PubMed

2018-01-01

Original article: Zilioli, S., Slatcher, R. B., Chi, P., Li, X., Zhao, J., & Zhao, G. (2016). Childhood adversity, self-esteem, and diurnal cortisol profiles across the life span. Psychological Science, 27, 1249-1265. doi:10.1177/0956797616658287.

Sibling Communication Functions across the Life-Span.

ERIC Educational Resources Information Center

Myers, Scott A.; Smith, Ronda L.; Sonnier, Michelle F.

An investigation examined whether perceived use of sibling functional communication skills differed across the life-span. Participants were recruited through university students enrolled in an introductory communication course at a southern university. All students received extra credit for recruiting two participants. Potential participants were…

Royal Darwinian Demons: Enforced Changes in Reproductive Efforts Do Not Affect the Life Expectancy of Ant Queens.

PubMed

Schrempf, Alexandra; Giehr, Julia; Röhrl, Ramona; Steigleder, Sarah; Heinze, Jürgen

2017-04-01

One of the central tenets of life-history theory is that organisms cannot simultaneously maximize all fitness components. This results in the fundamental trade-off between reproduction and life span known from numerous animals, including humans. Social insects are a well-known exception to this rule: reproductive queens outlive nonreproductive workers. Here, we take a step forward and show that under identical social and environmental conditions the fecundity-longevity trade-off is absent also within the queen caste. A change in reproduction did not alter life expectancy, and even a strong enforced increase in reproductive efforts did not reduce residual life span. Generally, egg-laying rate and life span were positively correlated. Queens of perennial social insects thus seem to maximize at the same time two fitness parameters that are normally negatively correlated. Even though they are not immortal, they best approach a hypothetical "Darwinian demon" in the animal kingdom.

Heart rate reduction and longevity in mice.

PubMed

Gent, Sabine; Kleinbongard, Petra; Dammann, Philip; Neuhäuser, Markus; Heusch, Gerd

2015-03-01

Heart rate correlates inversely with life span across all species, including humans. In patients with cardiovascular disease, higher heart rate is associated with increased mortality, and such patients benefit from pharmacological heart rate reduction. However, cause-and-effect relationships between heart rate and longevity, notably in healthy individuals, are not established. We therefore prospectively studied the effects of a life-long pharmacological heart rate reduction on longevity in mice. We hypothesized, that the total number of cardiac cycles is constant, and that a 15% heart rate reduction might translate into a 15% increase in life span. C57BL6/J mice received either placebo or ivabradine at a dose of 50 mg/kg/day in drinking water from 12 weeks to death. Heart rate and body weight were monitored. Autopsy was performed on all non-autolytic cadavers, and parenchymal organs were evaluated macroscopically. Ivabradine reduced heart rate by 14% (median, interquartile range 12-15%) throughout life, and median life span was increased by 6.2% (p = 0.01). Body weight and macroscopic findings were not different between placebo and ivabradine. Life span was not increased to the same extent as heart rate was reduced, but nevertheless significantly prolonged by 6.2%.

A cost–benefit analysis of acclimation to low irradiance in tropical rainforest tree seedlings: leaf life span and payback time for leaf deployment

PubMed Central

Coste, Sabrina; Roggy, Jean-Christophe; Schimann, Heidy; Epron, Daniel; Dreyer, Erwin

2011-01-01

The maintenance in the long run of a positive carbon balance under very low irradiance is a prerequisite for survival of tree seedlings below the canopy or in small gaps in a tropical rainforest. To provide a quantitative basis for this assumption, experiments were carried out to determine whether construction cost (CC) and payback time for leaves and support structures, as well as leaf life span (i) differ among species and (ii) display an irradiance-elicited plasticity. Experiments were also conducted to determine whether leaf life span correlates to CC and payback time and is close to the optimal longevity derived from an optimization model. Saplings from 13 tropical tree species were grown under three levels of irradiance. Specific-CC was computed, as well as CC scaled to leaf area at the metamer level. Photosynthesis was recorded over the leaf life span. Payback time was derived from CC and a simple photosynthesis model. Specific-CC displayed only little interspecific variability and irradiance-elicited plasticity, in contrast to CC scaled to leaf area. Leaf life span ranged from 4 months to >26 months among species, and was longest in seedlings grown under lowest irradiance. It was always much longer than payback time, even under the lowest irradiance. Leaves were shed when their photosynthesis had reached very low values, in contrast to what was predicted by an optimality model. The species ranking for the different traits was stable across irradiance treatments. The two pioneer species always displayed the smallest CC, leaf life span, and payback time. All species displayed a similar large irradiance-elicited plasticity. PMID:21511904

Developmental dyslexia: the visual attention span deficit hypothesis.

PubMed

Bosse, Marie-Line; Tainturier, Marie Josèphe; Valdois, Sylviane

2007-08-01

The visual attention (VA) span is defined as the amount of distinct visual elements which can be processed in parallel in a multi-element array. Both recent empirical data and theoretical accounts suggest that a VA span deficit might contribute to developmental dyslexia, independently of a phonological disorder. In this study, this hypothesis was assessed in two large samples of French and British dyslexic children whose performance was compared to that of chronological-age matched control children. Results of the French study show that the VA span capacities account for a substantial amount of unique variance in reading, as do phonological skills. The British study replicates this finding and further reveals that the contribution of the VA span to reading performance remains even after controlling IQ, verbal fluency, vocabulary and single letter identification skills, in addition to phoneme awareness. In both studies, most dyslexic children exhibit a selective phonological or VA span disorder. Overall, these findings support a multi-factorial view of developmental dyslexia. In many cases, developmental reading disorders do not seem to be due to phonological disorders. We propose that a VA span deficit is a likely alternative underlying cognitive deficit in dyslexia.

Older adults do not notice their names: a new twist to a classic attention task.

PubMed

Naveh-Benjamin, Moshe; Kilb, Angela; Maddox, Geoffrey B; Thomas, Jenna; Fine, Hope C; Chen, Tina; Cowan, Nelson

2014-11-01

Although working memory spans are, on average, lower for older adults than young adults, we demonstrate in 5 experiments a way in which older adults paradoxically resemble higher capacity young adults. Specifically, in a selective-listening task, older adults almost always failed to notice their names presented in an unattended channel. This is an exaggeration of what high-span young adults show and the opposite of what low-span young adults show. This striking finding in older adults remained significant after controlling for working memory span and for noticing their names in an attended channel. The findings were replicated when presentation rate was slowed and when the ear in which the unattended name was presented was controlled. These results point to an account of older adults' performance involving not only an inhibition factor, which allows high-span young adults to suppress the channel to be ignored, but also an attentional capacity factor, with more unallocated capacity. This capacity allows low-span young adults to notice their names much more often than older adults with comparably low working memory spans do. PsycINFO Database Record (c) 2014 APA, all rights reserved.

KIRA1 and ORESARA1 terminate flower receptivity by promoting cell death in the stigma of Arabidopsis.

PubMed

Gao, Zhen; Daneva, Anna; Salanenka, Yuliya; Van Durme, Matthias; Huysmans, Marlies; Lin, Zongcheng; De Winter, Freya; Vanneste, Steffen; Karimi, Mansour; Van de Velde, Jan; Vandepoele, Klaas; Van de Walle, Davy; Dewettinck, Koen; Lambrecht, Bart N; Nowack, Moritz K

2018-05-28

Flowers have a species-specific functional life span that determines the time window in which pollination, fertilization and seed set can occur. The stigma tissue plays a key role in flower receptivity by intercepting pollen and initiating pollen tube growth toward the ovary. In this article, we show that a developmentally controlled cell death programme terminates the functional life span of stigma cells in Arabidopsis. We identified the leaf senescence regulator ORESARA1 (also known as ANAC092) and the previously uncharacterized KIRA1 (also known as ANAC074) as partially redundant transcription factors that modulate stigma longevity by controlling the expression of programmed cell death-associated genes. KIRA1 expression is sufficient to induce cell death and terminate floral receptivity, whereas lack of both KIRA1 and ORESARA1 substantially increases stigma life span. Surprisingly, the extension of stigma longevity is accompanied by only a moderate extension of flower receptivity, suggesting that additional processes participate in the control of the flower's receptive life span.

Getting together: Social contact frequency across the life span.

PubMed

Sander, Julia; Schupp, Jürgen; Richter, David

2017-08-01

Frequent social interactions are strongly linked to positive affect, longevity, and good health. Although there has been extensive research on changes in the size of social networks over time, little attention has been given to the development of contact frequency across the life span. In this cohort-sequential longitudinal study, we examined intraindividual changes in the frequency of social contact with family and nonfamily members, and potential moderators of these changes. The data come from the 1998, 2003, 2008, and 2013 waves of the German Socio-Economic Panel (SOEP) study (N = 36,716; age range: 17-85 years). Using latent growth curve analysis, we found that the frequency of in-person contact with family members remained relatively stable across the life span. In contrast, the frequency of visits to and from nonfamily members (neighbors, friends, and acquaintances) declined following a cubic trajectory and dropped below the frequency of family visits when respondents were in their mid-30s. Relationship status and gender had a slight effect on both of these relationship trajectories. Subjective current health status and employment status influenced the life span trajectory of nonfamily social contact only. Changes of residence and the birth of a child, both of which constitute major turning points in the life course, did not affect the life span trajectory of either family or nonfamily in-person contact. The findings are discussed here in the context of earlier findings and in relation to socioemotional selectivity and social convoy theory and the evolutionary life history approach. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Effect of habitat preference on frond life span in three Cyathea tree ferns

NASA Astrophysics Data System (ADS)

Chiu, Tzu Yun; Wang, Hsiang Hua; Lun Kuo, Yao; Kume, Tomonori

2013-04-01

It has been reported that plants living in various geographical areas had different physiological forms, as factors of microenvironment have strong impacts on physiological characters. However, the physiological characters of fronds have been scarcely reported in ferns. In this study, we investigated physiological differences in response to the habitat preference in the three tree ferns in northeast Taiwan, Cyathea lepifera, C. spinulosa, and C. podophylla, prefer to open site, edge of forest, and interior forest, respectively. The canopy openness above the individuals of C. lepifera, C. spinulosa and C. podophylla were 29.2 ± 14.10 , 7.0 ± 3.07 and 5.0 ± 2.24 %, respectively. Among three species, C. podophylla had the longest frond life span (13.0 ± 4.12 months) than the two others (C. lepifera (6.8 ± 1.29 months) and C. spinulosa (7.3 ±1.35 months). Our result supported the general patterns that shade intolerant species have a shorter leaf life span than shade tolerant species. The maximum net CO2 assimilation of C. lepifera, C. spinulosa and C. podophylla were 11.46 ± 1.34, 8.27 ± 0.69, and 6.34 ± 0.54 μmol CO2 m-2 s-1, respectively. As well, C. lepifera had the highest photosynthetic light saturation point (LSP), while C. podophylla had the lowest LSP among these three tree ferns. These suggested that C. lepifera could be more efficient for capturing and utilizing light resources under the larger canopy openness condition than the other two species. We also found that frond C : N ratio were positively correlated with frond life span among species. C. podophylla, with the longest frond life span, had the highest frond C : N ratio (22.17 ± 1.95), which was followed by C. spinulosa (18.58 ± 1.37) and C. lepifera (18.68 ± 2.63) with shorter frond life span. The results were consistent to the theory that the fronds and leaves of shade intolerant species have high photosynthetic abilities with low C : N ratio. Key words: Canopy openness, frond life span, tree fern, Cyathea, frond C : N ratio

Origin of life in a digital microcosm

NASA Astrophysics Data System (ADS)

C G, Nitash; LaBar, Thomas; Hintze, Arend; Adami, Christoph

2017-11-01

While all organisms on Earth share a common descent, there is no consensus on whether the origin of the ancestral self-replicator was a one-off event or whether it only represented the final survivor of multiple origins. Here, we use the digital evolution system Avida to study the origin of self-replicating computer programs. By using a computational system, we avoid many of the uncertainties inherent in any biochemical system of self-replicators (while running the risk of ignoring a fundamental aspect of biochemistry). We generated the exhaustive set of minimal-genome self-replicators and analysed the network structure of this fitness landscape. We further examined the evolvability of these self-replicators and found that the evolvability of a self-replicator is dependent on its genomic architecture. We also studied the differential ability of replicators to take over the population when competed against each other, akin to a primordial-soup model of biogenesis, and found that the probability of a self-replicator outcompeting the others is not uniform. Instead, progenitor (most-recent common ancestor) genotypes are clustered in a small region of the replicator space. Our results demonstrate how computational systems can be used as test systems for hypotheses concerning the origin of life. This article is part of the themed issue 'Reconceptualizing the origins of life'.

Computational analysis of semi-span model test techniques

NASA Technical Reports Server (NTRS)

Milholen, William E., II; Chokani, Ndaona

1996-01-01

A computational investigation was conducted to support the development of a semi-span model test capability in the NASA LaRC's National Transonic Facility. This capability is required for the testing of high-lift systems at flight Reynolds numbers. A three-dimensional Navier-Stokes solver was used to compute the low-speed flow over both a full-span configuration and a semi-span configuration. The computational results were found to be in good agreement with the experimental data. The computational results indicate that the stand-off height has a strong influence on the flow over a semi-span model. The semi-span model adequately replicates the aerodynamic characteristics of the full-span configuration when a small stand-off height, approximately twice the tunnel empty sidewall boundary layer displacement thickness, is used. Several active sidewall boundary layer control techniques were examined including: upstream blowing, local jet blowing, and sidewall suction. Both upstream tangential blowing, and sidewall suction were found to minimize the separation of the sidewall boundary layer ahead of the semi-span model. The required mass flow rates are found to be practicable for testing in the NTF. For the configuration examined, the active sidewall boundary layer control techniques were found to be necessary only near the maximum lift conditions.

Post-dauer life span of Caenorhabditis elegans dauer larvae can be modified by X-irradiation.

PubMed

Onodera, Akira; Yanase, Sumino; Ishii, Takamasa; Yasuda, Kayo; Miyazawa, Masaki; Hartman, Philip S; Ishii, Naoaki

2010-01-01

The time spent as a dauer larva does not affect adult life span in Caenorhabditis elegans, as if aging is suspended in this quiescent developmental stage. We now report that modest doses X-irradiation of dauer larvae increased their post-dauer longevity. Post-irradiation incubation of young dauer larvae did not modify this beneficial effect of radiation. Conversely, holding dauer larvae prior to irradiation rendered them refractory to this X-radiation-induced response. We present a model to explain these results. These experiments demonstrate that dauer larvae provide an excellent opportunity to study mechanisms by which X irradiation can extend life span.

Spontaneous locomotor activity and life span. A test of the rate of living theory in Drosophila melanogaster.

PubMed

Lints, F A; Le Bourg, E; Lints, C V

1984-01-01

The spontaneous locomotor activity and life span of approximately 600 individuals of both sexes and of three widely different genotypes of Drosophila melanogaster have been measured. Neither at the individual nor at the populational level could a significant correlation between spontaneous locomotor activity and life span be found. The results are discussed in relation with Pearl's [The rate of living, London University Press, London 1928] rate of living theory. That theory has been tested in relation with environmental temperature, oxygen consumption and activity. It is shown that the theory has received no definite confirmation until now.

Feminist Developmental Theory: Implications for Counseling.

ERIC Educational Resources Information Center

Wastell, Colin A.

1996-01-01

Discusses the importance of counseling guided by a life-span development model. Emphasizes that one popular theory should be modified by taking into account a broader understanding of life-span development in terms of commonalities and differences in male and female development. Examines implications with borderline personality disorder and…

Target of Rapamycin Signaling Regulates Metabolism, Growth, and Life Span in Arabidopsis[W][OA

PubMed Central

Ren, Maozhi; Venglat, Prakash; Qiu, Shuqing; Feng, Li; Cao, Yongguo; Wang, Edwin; Xiang, Daoquan; Wang, Jinghe; Alexander, Danny; Chalivendra, Subbaiah; Logan, David; Mattoo, Autar; Selvaraj, Gopalan; Datla, Raju

2012-01-01

Target of Rapamycin (TOR) is a major nutrition and energy sensor that regulates growth and life span in yeast and animals. In plants, growth and life span are intertwined not only with nutrient acquisition from the soil and nutrition generation via photosynthesis but also with their unique modes of development and differentiation. How TOR functions in these processes has not yet been determined. To gain further insights, rapamycin-sensitive transgenic Arabidopsis thaliana lines (BP12) expressing yeast FK506 Binding Protein12 were developed. Inhibition of TOR in BP12 plants by rapamycin resulted in slower overall root, leaf, and shoot growth and development leading to poor nutrient uptake and light energy utilization. Experimental limitation of nutrient availability and light energy supply in wild-type Arabidopsis produced phenotypes observed with TOR knockdown plants, indicating a link between TOR signaling and nutrition/light energy status. Genetic and physiological studies together with RNA sequencing and metabolite analysis of TOR-suppressed lines revealed that TOR regulates development and life span in Arabidopsis by restructuring cell growth, carbon and nitrogen metabolism, gene expression, and rRNA and protein synthesis. Gain- and loss-of-function Ribosomal Protein S6 (RPS6) mutants additionally show that TOR function involves RPS6-mediated nutrition and light-dependent growth and life span in Arabidopsis. PMID:23275579

Yeast MRX deletions have short chronological life span and more triacylglycerols.

PubMed

Kanagavijayan, Dhanabalan; Rajasekharan, Ram; Srinivasan, Malathi

2016-02-01

Saccharomyces cerevisiae is an excellent model organism for lipid research. Here, we have used yeast haploid RAdiation Damage (RAD) deletion strains to study life span and lipid storage patterns. RAD genes are mainly involved in DNA repair mechanism and hence, their deletions have resulted in shorter life span. Viable RAD mutants were screened for non-polar lipid content, and some of the mutants showed significantly high amounts of triacylglycerol (TAG) and steryl ester, besides short chronological life span. Among these, RAD50, MRE11 and XRS2 form a complex, MRX that is involved in homologous recombination that showed an increase in the amount of TAG. Microarray data of single MRX deletions revealed that besides DNA damage signature genes, lipid metabolism genes are also differentially expressed. Lipid biosynthetic genes (LPP1, SLC1) were upregulated and lipid hydrolytic gene (TGL3) was downregulated. We observed that rad50Δ, mre11Δ, xrs2Δ and mrxΔ strains have high number of lipid droplets (LDs) with fragmented mitochondria. These mutants have a short chronological life span compared to wild type. Aged wild-type cells also accumulated TAG with LDs of ∼2.0 μm in diameter. These results suggest that TAG accumulation and big size LDs could be possible markers for premature or normal aging. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Like cognitive function, decision making across the life span shows profound age-related changes.

PubMed

Tymula, Agnieszka; Rosenberg Belmaker, Lior A; Ruderman, Lital; Glimcher, Paul W; Levy, Ifat

2013-10-15

It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain.

"Life-span development of visual working memory: When is feature binding difficult?": Correction to Cowan et al. (2006).

PubMed

2016-10-01

Reports an error in "Life-span development of visual working memory: When is feature binding difficult?" by Nelson Cowan, Moshe Naveh-Benjamin, Angela Kilb and J. Scott Saults ( Developmental Psychology , 2006[Nov], Vol 42[6], 1089-1102). In the article, there were two errors in experiment 1a. The mean for color item information in older adults was incorrectly calculated. As a result, Figure 3 shows a mean of over .70. The true mean was .63 ( SEM =.04). This change diminishes the magnitude of the aging deficit for associative information, although this deficit still appears to remain, to a smaller extent. (For a conceptual replication see Peterson & Naveh-Benjamin, 2016). There also was an error in the experimental procedure of Experiment 1a. The older adults in that experiment received only half the number of trials specified in the methods section, and half as much as the other groups. For all groups, when there were 4 or 6 items and the probe was a binding change, the probed location was matched by the same color at 1 other location but, when there were 8 or 10 squares, the probed location was matched by the same color at 1, 2, or 3 other locations. For 8 squares the number of trials was identical for these three trial subtypes whereas, for 10 squares, most of the trials had the same color at just 1 other location. These errors suggest that the experiment should be taken as only preliminary evidence that there is an aging deficit in color-location binding in visual working memory when color and binding trials are mixed in the same trial blocks. (The following abstract of the original article appeared in record 2006-20488-009.) We asked whether the ability to keep in working memory the binding between a visual object and its spatial location changes with development across the life span more than memory for item information. Paired arrays of colored squares were identical or differed in the color of one square, and in the latter case, the changed color was unique on that trial (item change) or was duplicated elsewhere in the array (color-location binding change). Children (8-10 and 11-12 years old) and older adults (65-85 years old) showed deficits relative to young adults. These were only partly simulated by dividing attention in young adults. The older adults had an additional deficiency, specifically in binding information, which was evident only when item- and binding-change trials were mixed together. In that situation, the older adults often overlooked the more subtle, binding-type changes. Some working memory processes related to binding undergo life-span development in an inverted-U shape, whereas other, bias- and salience-related processes that influence the use of binding information seem to develop monotonically. PsycINFO Database Record (c) 2016 APA, all rights reserved

View of central lift span truss web of Tensaw River ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View of central lift span truss web of Tensaw River Bridge, showing support girders for life house, looking east - Tensaw River Lift Bridge, Spanning Tensaw River at U.S. Highway 90, Mobile, Mobile County, AL

Hepatitis B Virus Polymerase Localizes to the Mitochondria, and Its Terminal Protein Domain Contains the Mitochondrial Targeting Signal.

PubMed

Unchwaniwala, Nuruddin; Sherer, Nathan M; Loeb, Daniel D

2016-10-01

To understand subcellular sites of hepatitis B virus (HBV) replication, we visualized core (Cp), polymerase (Pol), and pregenomic RNA (pgRNA) in infected cells. Interestingly, we found that the majority of Pol localized to the mitochondria in cells undergoing viral replication. The mitochondrial localization of Pol was independent of both the cell type and other viral components, indicating that Pol contains an intrinsic mitochondrial targeting signal (MTS). Neither Cp nor pgRNA localized to the mitochondria during active replication, suggesting a role other than DNA synthesis for Pol at the mitochondria. The Pol of duck hepatitis B virus (DHBV) also localized to the mitochondria. This result indicates that localization of Pol to mitochondria is likely a feature of all hepadnaviruses. To map the MTS within HBV Pol, we generated a series of Pol-green fluorescent protein (Pol-GFP) fusions and found that a stretch spanning amino acids (aa) 141 to 160 of Pol was sufficient to target GFP to the mitochondria. Surprisingly, deleting aa 141 to 160 in full-length Pol did not fully ablate Pol's mitochondrial localization, suggesting that additional sequences are involved in mitochondrial targeting. Only by deleting the N-terminal 160 amino acids in full-length Pol was mitochondrial localization ablated. Crucial residues for pgRNA packaging are contained within aa 141 to 160, indicating a multifunctional role of this region of Pol in the viral life cycle. Our studies show an unexpected Pol trafficking behavior that is uncoupled from its role in viral DNA synthesis. Chronic infection by HBV is a serious health concern. Existing therapies for chronically infected individuals are not curative, underscoring the need for a better understanding of the viral life cycle to develop better antiviral therapies. To date, the most thoroughly studied function of Pol is to package the pgRNA and reverse transcribe it to double-stranded DNA within capsids. This study provides evidence for mitochondrial localization of Pol and defines the MTS. Recent findings have implicated a non-reverse transcription role for Pol in evading host innate immune responses. Mitochondria play an important role in controlling cellular metabolism, apoptosis, and innate immunity. Pol may alter one or more of these host mitochondrial functions to gain a replicative advantage and persist in chronically infected individuals. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Structural diversity and dynamics of genomic replication origins in Schizosaccharomyces pombe

PubMed Central

Cotobal, Cristina; Segurado, Mónica; Antequera, Francisco

2010-01-01

DNA replication origins (ORI) in Schizosaccharomyces pombe colocalize with adenine and thymine (A+T)-rich regions, and earlier analyses have established a size from 0.5 to over 3 kb for a DNA fragment to drive replication in plasmid assays. We have asked what are the requirements for ORI function in the chromosomal context. By designing artificial ORIs, we have found that A+T-rich fragments as short as 100 bp without homology to S. pombe DNA are able to initiate replication in the genome. On the other hand, functional dissection of endogenous ORIs has revealed that some of them span a few kilobases and include several modules that may be as short as 25–30 contiguous A+Ts capable of initiating replication from ectopic chromosome positions. The search for elements with these characteristics across the genome has uncovered an earlier unnoticed class of low-efficiency ORIs that fire late during S phase. These results indicate that ORI specification and dynamics varies widely in S. pombe, ranging from very short elements to large regions reminiscent of replication initiation zones in mammals. PMID:20094030

FACT SHEET: EPA ISSUES UPDATED CANCER GUIDELINES AND SUPPLEMENTAL GUIDANCE ON RISKS FROM EARLY-LIFE EXPOSURE

EPA Science Inventory

March 29, 2005

FACT SHEET: Women's Spirituality across the Life Span: Implications for Counseling

ERIC Educational Resources Information Center

Briggs, Michele Kielty; Dixon, Andrea L.

2013-01-01

Women's spirituality has unique characteristics that are often ignored within the spirituality literature. The authors review the literature on women's spirituality to reveal the major themes women have identified as relevant to their spiritual journeys across the life span. Implications for counseling and ideas for practice are included after…

Spatial Abilities across the Adult Life Span

ERIC Educational Resources Information Center

Borella, Erika; Meneghetti, Chiara; Ronconi, Lucia; De Beni, Rossana

2014-01-01

The study investigates age-related effects across the adult life span on spatial abilities (testing subabilities based on a distinction between spatial visualization, mental rotation, and perspective taking) and spatial self-assessments. The sample consisted of 454 participants (223 women and 231 men) from 20 to 91 years of age. Results showed…

Sensorimotor Synchronization across the Life Span

ERIC Educational Resources Information Center

Drewing, Knut; Aschersleben, Gisa; Li, Shu-Chen

2006-01-01

The present study investigates the contribution of general processing resources as well as other more specific factors to the life-span development of sensorimotor synchronization and its component processes. Within a synchronization tapping paradigm, a group of 286 participants, 6 to 88 years of age, were asked to synchronize finger taps with…

Sex-Role Inconstancy, Biology, and Successful Aging: A Dialectical Model

ERIC Educational Resources Information Center

Sinnott, Jan Dynda

1977-01-01

This paper examines sex-role inconstancy from a life-span point of view. New environmental realities and an increasing life-span may make traditional sex roles less functional in old age. Evidence is presented for more successful aging in persons manifesting convergent sex-role behavior. (Author)

Redesign of a Life Span Development Course Using Fink's Taxonomy

ERIC Educational Resources Information Center

Fallahi, Carolyn R.

2008-01-01

This study compared a traditional lecture-based life span development course to the same course redesigned using Fink's (2003) taxonomy of significant learning. The goals, activities, and feedback within the course corresponded to Fink's 6 taxa (knowledge, application, integration, human dimension, caring, learning how to learn). Undergraduates in…

Neuromodulation of Behavioral and Cognitive Development across the Life Span

ERIC Educational Resources Information Center

Li, Shu-Chen

2012-01-01

Among other mechanisms, behavioral and cognitive development entail, on the one hand, contextual scaffolding and, on the other hand, neuromodulation of adaptive neurocognitive representations across the life span. Key brain networks underlying cognition, emotion, and motivation are innervated by major transmitter systems (e.g., the catecholamines…

Vitamins and aging: pathways to NAD+ synthesis.

PubMed

Denu, John M

2007-05-04

Recent genetic evidence reveals additional salvage pathways for NAD(+) synthesis. In this issue, Belenky et al. (2007) report that nicotinamide riboside, a new NAD(+) precursor, regulates Sir2 deacetylase activity and life span in yeast. The ability of nicotinamide riboside to enhance life span does not depend on calorie restriction.

Large-brained frogs mature later and live longer.

PubMed

Yu, Xin; Zhong, Mao Jun; Li, Da Yong; Jin, Long; Liao, Wen Bo; Kotrschal, Alexander

2018-05-01

Brain sizes vary substantially across vertebrate taxa, yet, the evolution of brain size appears tightly linked to the evolution of life histories. For example, larger brained species generally live longer than smaller brained species. A larger brain requires more time to grow and develop at a cost of exceeded gestation period and delayed weaning age. The cost of slower development may be compensated by better homeostasis control and increased cognitive abilities, both of which should increase survival probabilities and hence life span. To date, this relationship between life span and brain size seems well established in homoeothermic animals, especially in mammals. Whether this pattern occurs also in other clades of vertebrates remains enigmatic. Here, we undertake the first comparative test of the relationship between life span and brain size in an ectothermic vertebrate group, the anuran amphibians. After controlling for the effects of shared ancestry and body size, we find a positive correlation between brain size, age at sexual maturation, and life span across 40 species of frogs. Moreover, we also find that the ventral brain regions, including the olfactory bulbs, are larger in long-lived species. Our results indicate that the relationship between life history and brain evolution follows a general pattern across vertebrate clades. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Mutant analysis of Cdt1's function in suppressing nascent strand elongation during DNA replication in Xenopus egg extracts.

PubMed

Nakazaki, Yuta; Tsuyama, Takashi; Azuma, Yutaro; Takahashi, Mikiko; Tada, Shusuke

2017-09-02

The initiation of DNA replication is strictly regulated by multiple mechanisms to ensure precise duplication of chromosomes. In higher eukaryotes, activity of the Cdt1 protein is temporally regulated during the cell cycle, and deregulation of Cdt1 induces DNA re-replication. In previous studies, we showed that excess Cdt1 inhibits DNA replication by suppressing progression of replication forks in Xenopus egg extracts. Here, we investigated the functional regions of Cdt1 that are required for the inhibition of DNA replication. We constructed a series of N-terminally or C-terminally deleted mutants of Cdt1 and examined their inhibitory effects on DNA replication in Xenopus egg extracts. Our results showed that the region spanning amino acids (a. a.) 255-620 is required for efficient inhibition of DNA replication, and that, within this region, a. a. 255-289 have a critical role in inhibition. Moreover, one of the Cdt1 mutants, Cdt1 R285A, was compromised with respect to the licensing activity but still inhibited DNA replication. This result suggests that Cdt1 has an unforeseen function in the negative regulation of DNA replication, and that this function is located within a molecular region that is distinct from those required for the licensing activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Megabase replication domains along the human genome: relation to chromatin structure and genome organisation.

PubMed

Audit, Benjamin; Zaghloul, Lamia; Baker, Antoine; Arneodo, Alain; Chen, Chun-Long; d'Aubenton-Carafa, Yves; Thermes, Claude

2013-01-01

In higher eukaryotes, the absence of specific sequence motifs, marking the origins of replication has been a serious hindrance to the understanding of (i) the mechanisms that regulate the spatio-temporal replication program, and (ii) the links between origins activation, chromatin structure and transcription. In this chapter, we review the partitioning of the human genome into megabased-size replication domains delineated as N-shaped motifs in the strand compositional asymmetry profiles. They collectively span 28.3% of the genome and are bordered by more than 1,000 putative replication origins. We recapitulate the comparison of this partition of the human genome with high-resolution experimental data that confirms that replication domain borders are likely to be preferential replication initiation zones in the germline. In addition, we highlight the specific distribution of experimental and numerical chromatin marks along replication domains. Domain borders correspond to particular open chromatin regions, possibly encoded in the DNA sequence, and around which replication and transcription are highly coordinated. These regions also present a high evolutionary breakpoint density, suggesting that susceptibility to breakage might be linked to local open chromatin fiber state. Altogether, this chapter presents a compartmentalization of the human genome into replication domains that are landmarks of the human genome organization and are likely to play a key role in genome dynamics during evolution and in pathological situations.

Lactobacillus salivarius strain FDB89 induced longevity in Caenorhabditis elegans by dietary restriction.

PubMed

Zhao, Yang; Zhao, Liang; Zheng, Xiaonan; Fu, Tianjiao; Guo, Huiyuan; Ren, Fazheng

2013-04-01

In this study, we utilized the nematode Caenorhabditis elegans to assess potential life-expanding effect of Lactobacillus salivarius strain FDB89 (FDB89) isolated from feces of centenarians in Bama County (Guangxi, China). This study showed that feeding FDB89 extended the mean life span in C. elegans by up to 11.9% compared to that of control nematodes. The reduced reproductive capacities, pharyngeal pumping rate, growth, and increased superoxide dismutase (SOD) activity and XTT reduction capacity were also observed in FDB89 feeding worms. To probe the anti-aging mechanism further, we incorporated a food gradient feeding assay and assayed the life span of eat-2 mutant. The results demonstrated that the maximal life span of C. elegans fed on FDB89 was achieved at the concentration of 1.0 mg bacterial cells/plate, which was 10-fold greater than that of C. elegans fed on E. coli OP50 (0.1 mg bacterial cells/plate). However, feeding FDB89 could not further extend the life span of eat-2 mutant. These results indicated that FDB89 modulated the longevity of C. elegans in a dietary restriction-dependent manner and expanded the understanding of anti-aging effect of probiotics.

The archaebacterial origin of eukaryotes.

PubMed

Cox, Cymon J; Foster, Peter G; Hirt, Robert P; Harris, Simon R; Embley, T Martin

2008-12-23

The origin of the eukaryotic genetic apparatus is thought to be central to understanding the evolution of the eukaryotic cell. Disagreement about the source of the relevant genes has spawned competing hypotheses for the origins of the eukaryote nuclear lineage. The iconic rooted 3-domains tree of life shows eukaryotes and archaebacteria as separate groups that share a common ancestor to the exclusion of eubacteria. By contrast, the eocyte hypothesis has eukaryotes originating within the archaebacteria and sharing a common ancestor with a particular group called the Crenarchaeota or eocytes. Here, we have investigated the relative support for each hypothesis from analysis of 53 genes spanning the 3 domains, including essential components of the eukaryotic nucleic acid replication, transcription, and translation apparatus. As an important component of our analysis, we investigated the fit between model and data with respect to composition. Compositional heterogeneity is a pervasive problem for reconstruction of ancient relationships, which, if ignored, can produce an incorrect tree with strong support. To mitigate its effects, we used phylogenetic models that allow for changing nucleotide or amino acid compositions over the tree and data. Our analyses favor a topology that supports the eocyte hypothesis rather than archaebacterial monophyly and the 3-domains tree of life.

Friendship in childhood and adulthood: lessons across the life span.

PubMed

Sherman, A M; de Vries, B; Lansford, J E

2000-01-01

Friendship occupies an important place in the growing body of literature in child development and gerontological research. As such, it may be useful for researchers from both fields to consider what can be learned from work carried out in each tradition. Therefore, we present a selected review of topics in friendship research across the life span. Through discussion of the value of friendship, the development of friendship, challenges to friendship, the gendered nature of friendship, and the connection between friends and family, points of commonality and contrast are identified. We conclude by presenting possible avenues for future investigation for researchers interested in friendship at any point in the life span.

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

PubMed

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.

Age Stereotypes and Self-Views Revisited: Patterns of Internalization and Projection Processes Across the Life Span.

PubMed

Kornadt, Anna E; Voss, Peggy; Rothermund, Klaus

2017-07-01

We investigated processes of age stereotype internalization into the self and projection of self-views onto age stereotypes from a life-span perspective, taking age-related differences in the relevance of life domains into account. Age stereotypes and self-views in eight life domains were assessed in a sample of N = 593 persons aged 30-80 years (T1) at two time points that were separated by a 4-year time interval. We estimated cross-lagged projection and internalization effects in multigroup structural equation models. Internalization and projection effects were contingent on age group and life domain: Internalization effects were strongest in the young and middle-aged groups and emerged in the domains family, personality, work, and leisure. Projection effects in different domains were most pronounced for older participants. Our findings suggest that the internalization of age stereotypes is triggered by domain-specific expectations of impending age-related changes and transitions during certain phases of the life span. Projection processes, however, seem to occur in response to changes that have already been experienced by the individual. Our study demonstrates the dynamic interrelation of age stereotypes and self-views across the life course and highlights the importance of a differentiated, life-span perspective for the understanding of these mechanisms. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Attachment and the Processing of Social Information across the Life Span: Theory and Evidence

ERIC Educational Resources Information Center

Dykas, Matthew J.; Cassidy, Jude

2011-01-01

Researchers have used J. Bowlby's (1969/1982, 1973, 1980, 1988) attachment theory frequently as a basis for examining whether experiences in close personal relationships relate to the processing of social information across childhood, adolescence, and adulthood. We present an integrative life-span-encompassing theoretical model to explain the…

Effects of a Short Strategy Training on Metacognitive Monitoring across the Life-Span

ERIC Educational Resources Information Center

von der Linden, Nicole; Löffler, Elisabeth; Schneider, Wolfgang

2015-01-01

The present study was conducted to explore the potential positive influence of a short strategy training on metacognitive monitoring competencies covering a life-span approach. Participants of four age groups (3rd-grade children, adolescents, younger and older adults) concluded a paired-associate learning task. Additionally, they gave delayed…

Psychopathology in Williams Syndrome: The Effect of Individual Differences across the Life Span

ERIC Educational Resources Information Center

Dodd, Helen F.; Porter, Melanie A.

2009-01-01

This research aimed to comprehensively explore psychopathology in Williams syndrome (WS) across the life span and evaluate the relationship between psychopathology and age category (child or adult), gender, and cognitive ability. The parents of 50 participants with WS, ages 6-50 years, were interviewed using the Schedule for Affective Disorders…

Influence of Domain Knowledge on Monitoring Performance across the Life Span

ERIC Educational Resources Information Center

Löffler, Elisabeth; von der Linden, Nicole; Schneider, Wolfgang

2016-01-01

Two studies were conducted to investigate effects of domain knowledge on metacognitive monitoring across the life span in materials of different complexity. Participants from 4 age groups (3rd-grade children, adolescents, younger and older adults) were compared using an expert-novice paradigm. In Study 1, soccer experts' and novices'…

Reading through the Life Span: Individual Differences in Psycholinguistic Effects

ERIC Educational Resources Information Center

Davies, Rob A. I.; Arnell, Ruth; Birchenough, Julia M. H.; Grimmond, Debbie; Houlson, Sam

2017-01-01

The effects of psycholinguistic variables are critical to the evaluation of theories about the cognitive reading system. However, reading research has tended to focus on the impact of key variables on average performance. We report the first investigation examining variation in psycholinguistic effects across the life span, from childhood into old…

Getting Together: Social Contact Frequency across the Life Span

ERIC Educational Resources Information Center

Sander, Julia; Schupp, Jürgen; Richter, David

2017-01-01

Frequent social interactions are strongly linked to positive affect, longevity, and good health. Although there has been extensive research on changes in the size of social networks over time, little attention has been given to the development of contact frequency across the life span. In this cohort-sequential longitudinal study, we examined…

Thermoregulatory, Cardiovascular, and Metabolic Responses to Mild Caloric Restriction in the Brown Norway Rat

EPA Science Inventory

Caloric restriction (CR) has been demonstrated to prolong the life span of a variety of species. CR-induced reduction in core temperature (Tc) is considered a key mechanism responsible for prolonging life span in rodents; however, little is known on the regulation of CR-induced h...

Assistive Device Use in Visually Impaired Older Adults: Role of Control Beliefs

ERIC Educational Resources Information Center

Becker, Stefanie; Wahl, Hans-Werner; Schilling, Oliver; Burmedi, David

2005-01-01

Purpose: We investigate whether psychological control, conceptually framed within the life-span theory of control by Heckhausen and Schulz, drives assistive device use in visually impaired elders. In particular, we expect the two primary control modes differentiated in the life-span theory of control (i.e., selective primary and compensatory…

Body Image across the Life Span in Adult Women: The Role of Self-Objectification.

ERIC Educational Resources Information Center

Tiggemann, Marika; Lynch, Jessica E.

2001-01-01

Investigated body image across life span in cross-section of women ages 20-84 years. Found that although body dissatisfaction remained stable, self-objectification, habitual body monitoring, appearance anxiety, and disordered eating all significantly decreased with age. Self- objectification mediated the relationship between age and disordered…

Dopa decarboxylase (Ddc) affects variation in Drosophila longevity.

PubMed

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

2003-08-01

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

The development of memory efficiency and value-directed remembering across the life span: a cross-sectional study of memory and selectivity.

PubMed

Castel, Alan D; Humphreys, Kathryn L; Lee, Steve S; Galván, Adriana; Balota, David A; McCabe, David P

2011-11-01

Although attentional control and memory change considerably across the life span, no research has examined how the ability to strategically remember important information (i.e., value-directed remembering) changes from childhood to old age. The present study examined this in different age groups across the life span (N = 320, 5-96 years old). A selectivity task was used in which participants were asked to study and recall items worth different point values in order to maximize their point score. This procedure allowed for measures of memory quantity/capacity (number of words recalled) and memory efficiency/selectivity (the recall of high-value items relative to low-value items). Age-related differences were found for memory capacity, as young adults recalled more words than the other groups. However, in terms of selectivity, younger and older adults were more selective than adolescents and children. The dissociation between these measures across the life span illustrates important age-related differences in terms of memory capacity and the ability to selectively remember high-value information.

Dietary Interventions to Extend Life Span and Health Span Based on Calorie Restriction

PubMed Central

Minor, Robin K.; Allard, Joanne S.; Younts, Caitlin M.; Ward, Theresa M.

2010-01-01

The societal impact of obesity, diabetes, and other metabolic disorders continues to rise despite increasing evidence of their negative long-term consequences on health span, longevity, and aging. Unfortunately, dietary management and exercise frequently fail as remedies, underscoring the need for the development of alternative interventions to successfully treat metabolic disorders and enhance life span and health span. Using calorie restriction (CR)—which is well known to improve both health and longevity in controlled studies—as their benchmark, gerontologists are coming closer to identifying dietary and pharmacological therapies that may be applicable to aging humans. This review covers some of the more promising interventions targeted to affect pathways implicated in the aging process as well as variations on classical CR that may be better suited to human adaptation. PMID:20371545

Clickers in the Classroom: A Review and a Replication

ERIC Educational Resources Information Center

Keough, Shawn M.

2012-01-01

This article reviews 66 clicker technology-based studies focusing on student perceptions/outcomes. Eight major perceptions/outcomes are noted, including high levels of performance (actual and perceived), student attention span, attendance, and participation, as well as student perceptions of satisfaction, feedback, and ease of use. Because the…

Pervasive gene expression responses to a fluctuating diet in Drosophila melanogaster: The importance of measuring multiple traits to decouple potential mediators of life span and reproduction.

PubMed

Zandveld, Jelle; van den Heuvel, Joost; Mulder, Maarten; Brakefield, Paul M; Kirkwood, Thomas B L; Shanley, Daryl P; Zwaan, Bas J

2017-11-01

Phenotypic plasticity is an important concept in life-history evolution, and most organisms, including Drosophila melanogaster, show a plastic life-history response to diet. However, little is known about how these life-history responses are mediated. In this study, we compared adult female flies fed an alternating diet (yoyo flies) with flies fed a constant low (CL) or high (CH) diet and tested how whole genome expression was affected by these diet regimes and how the transcriptional responses related to different life-history traits. We showed that flies were able to respond quickly to diet fluctuations throughout life span by drastically changing their transcription. Importantly, by measuring the response of multiple life-history traits we were able to decouple groups of genes associated with life span or reproduction, life-history traits that often covary with a diet change. A coexpression network analysis uncovered which genes underpin the separate and shared regulation of these life-history traits. Our study provides essential insights to help unravel the genetic architecture mediating life-history responses to diet, and it shows that the flies' whole genome transcription response is highly plastic. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Age Differences and Educational Attainment across the Life Span on Three Generations of Wechsler Adult Scales

ERIC Educational Resources Information Center

Kaufman, A. S.; Salthouse, T. A.; Scheiber, C.; Chen, H.

2016-01-01

Patterns of maintenance of ability across the life span have been documented on tests of knowledge ("Gc"), as have patterns of steady decline on measures of reasoning ("Gf/Gv"), working memory ("Gsm"), and speed ("Gs"). Whether these patterns occur at the same rate for adults from different educational…

Age Differences in Five Personality Domains across the Life Span

ERIC Educational Resources Information Center

Allemand, Mathias; Zimprich, Daniel; Hendriks, A. A. Jolijn

2008-01-01

The present study addresses the issue of age differences in 5 personality domains across the life span in a cross-sectional study. In contrast to most previous studies, the present study follows a methodologically more rigorous approach to warrant that age-related differences in personality structure and mean level can be meaningfully compared. It…

Developmental Change in Proactive Interference across the Life Span: Evidence from Two Working Memory Tasks

ERIC Educational Resources Information Center

Loosli, Sandra V.; Rahm, Benjamin; Unterrainer, Josef M.; Weiller, Cornelius; Kaller, Christoph P.

2014-01-01

Working memory (WM) as the ability to temporarily maintain and manipulate various kinds of information is known to be affected by proactive interference (PI) from previously relevant contents, but studies on developmental changes in the susceptibility to PI are scarce. In the present study, we investigated life span development of item-specific…

Life-Span Issues in the Fair and Non-Discriminatory Evaluation of Workers.

ERIC Educational Resources Information Center

Alexander, Ralph A.; Barrett, Gerald V.

Until recently, older workers have not been recognized as a group requiring special attention in the area of fair employment practices. Thus, progress has been slow towards the development of valid and reliable indices of performance which are applicable across the life span. Research shows that many measures of employee evaluation provide no…

Essentialist Reasoning and Knowledge Effects on Biological Reasoning in Young Children

ERIC Educational Resources Information Center

Herrmann, Patricia A.; French, Jason A.; DeHart, Ganie B.; Rosengren, Karl S.

2013-01-01

Biological kinds undergo a variety of changes during their life span, and these changes vary in degree by organism. Understanding that an organism, such as a caterpillar, maintains category identity over its life span despite dramatic changes is a key concept in biological reasoning. At present, we know little about the developmental trajectory of…

Emerging critical roles of Fe-S clusters in DNA replication and repair

PubMed Central

Fuss, Jill O.; Tsai, Chi-Lin; Ishida, Justin P.; Tainer, John A.

2015-01-01

Fe-S clusters are partners in the origin of life that predate cells, acetyl-CoA metabolism, DNA, and the RNA world. The double helix solved the mystery of DNA replication by base pairing for accurate copying. Yet, for genome stability necessary to life, the double helix has equally important implications for damage repair. Here we examine striking advances that uncover Fe-S cluster roles both in copying the genetic sequence by DNA polymerases and in crucial repair processes for genome maintenance, as mutational defects cause cancer and degenerative disease. Moreover, we examine an exciting, controversial role for Fe-S clusters in a third element required for life – the long-range coordination and regulation of replication and repair events. By their ability to delocalize electrons over both Fe and S centers, Fe-S clusters have unbeatable features for protein conformational control and charge transfer via double-stranded DNA that may fundamentally transform our understanding of life, replication, and repair. PMID:25655665

Continuous cell lines from the Muscovy duck as potential replacement for primary cells in the production of avian vaccines.

PubMed

Jordan, Ingo; John, Katrin; Höwing, Kristin; Lohr, Verena; Penzes, Zoltán; Gubucz-Sombor, Erzsébet; Fu, Yan; Gao, Peng; Harder, Timm; Zádori, Zoltán; Sandig, Volker

2016-01-01

Veterinary vaccines contribute to food security, interrupt zoonotic transmissions, and help to maintain overall health in livestock. Although vaccines are usually cost-effective, their adoption depends on a multitude of factors. Because poultry vaccines are usually given to birds with a short life span, very low production cost per dose is one important challenge. Other hurdles are to ensure a consistent and reliable supply of very large number of doses, and to have flexible production processes to accommodate a range of different pathogens and dosage requirements. Most poultry vaccines are currently being produced on primary avian cells derived from chicken or waterfowl embryos. This production system is associated with high costs, logistic complexities, rigid intervals between harvest and production, and supply limitations. We investigated whether the continuous cell lines Cairina retina and CR.pIX may provide a substrate independent of primary cell cultures or embryonated eggs. Viruses examined for replication in these cell lines are strains associated with, or contained in vaccines against egg drop syndrome, Marek's disease, Newcastle disease, avian influenza, infectious bursal disease and Derzsy's disease. Each of the tested viruses required the development of unique conditions for replication that are described here and can be used to generate material for in vivo efficacy studies and to accelerate transfer of the processes to larger production volumes.

Aiding the search: Examining individual differences in multiply-constrained problem solving.

PubMed

Ellis, Derek M; Brewer, Gene A

2018-07-01

Understanding and resolving complex problems is of vital importance in daily life. Problems can be defined by the limitations they place on the problem solver. Multiply-constrained problems are traditionally examined with the compound remote associates task (CRAT). Performance on the CRAT is partially dependent on an individual's working memory capacity (WMC). These findings suggest that executive processes are critical for problem solving and that there are reliable individual differences in multiply-constrained problem solving abilities. The goals of the current study are to replicate and further elucidate the relation between WMC and CRAT performance. To achieve these goals, we manipulated preexposure to CRAT solutions and measured WMC with complex-span tasks. In Experiment 1, we report evidence that preexposure to CRAT solutions improved problem solving accuracy, WMC was correlated with problem solving accuracy, and that WMC did not moderate the effect of preexposure on problem solving accuracy. In Experiment 2, we preexposed participants to correct and incorrect solutions. We replicated Experiment 1 and found that WMC moderates the effect of exposure to CRAT solutions such that high WMC participants benefit more from preexposure to correct solutions than low WMC (although low WMC participants have preexposure benefits as well). Broadly, these results are consistent with theories of working memory and problem solving that suggest a mediating role of attention control processes. Published by Elsevier Inc.

Cell longevity and sustained primary growth in palm stems.

PubMed

Tomlinson, P Barry; Huggett, Brett A

2012-12-01

Longevity, or organismal life span, is determined largely by the period over which constituent cells can function metabolically. Plants, with modular organization (the ability continually to develop new organs and tissues) differ from animals, with unitary organization (a fixed body plan), and this difference is reflected in their respective life spans, potentially much longer in plants than animals. We draw attention to the observation that palm trees, as a group of monocotyledons without secondary growth comparable to that of lignophytes (plants with secondary growth from a bifacial cambium), retain by means of sustained primary growth living cells in their trunks throughout their organismal life span. Does this make palms the longest-lived trees because they can grow as individuals for several centuries? No conventional lignophyte retains living metabolically active differentiated cell types in its trunk for this length of time, even though the tree as a whole can exist for millennia. Does this contrast also imply that the long-lived cells in a palm trunk have exceptional properties, which allows this seeming immortality? We document the long-life of many tall palm species and their inherent long-lived stem cell properties, comparing such plants to conventional trees. We provide a summary of aspects of cell age and life span in animals and plants. Cell replacement is a feature of animal function, whereas conventional trees rely on active growth centers (meristems) to sustain organismal development. However, the long persistence of living cells in palm trunks is seen not as evidence for unique metabolic processes that sustain longevity, but is a consequence of unique constructional features. This conclusion suggests that the life span of plant cells is not necessarily genetically determined.

From menarche to menopause: the fertile life span of celiac women.

PubMed

Santonicola, Antonella; Iovino, Paola; Cappello, Carmelina; Capone, Pietro; Andreozzi, Paolo; Ciacci, Carolina

2011-10-01

We evaluated menopause-associated disorders and fertile life span in women with celiac disease (CD) under untreated conditions and after long-term treatment with a gluten-free diet. The participants were 33 women with CD after menopause (untreated CD group), 25 celiac women consuming a gluten-free diet at least 10 years before menopause (treated CD group), and 45 healthy volunteers (control group). The Menopause Rating Scale questionnaire was used to gather information on menopause-associated disorders. The International Physical Activity Questionnaire was used to acquire information on physical activity. Untreated celiac women had a shorter duration of fertile life span than did the control women because of an older age of menarche and a younger age of menopause (P < 0.01). The scores for hot flushes, muscle/joint problems, and irritability were higher in untreated celiac women than in the control women (higher by 49.4%, 121.4%, and 58.6%, respectively; P < 0.05). In comparison with untreated CD, long-lasting treatment of CD was not associated with a significant difference in the duration of fertile life span, but was only associated with a significant reduction in muscle/joint problems (a reduction of 47.1%; P < 0.05). Late menarche and early menopause causes a shorter fertile period in untreated celiac women compared with control women. A gluten-free diet that started at least 10 years before menopause prolongs the fertile life span of celiac women. The perception of intensity of hot flushes and irritability is more severe in untreated celiac women than in controls. Low physical exercise and/or poorer quality of life frequently reported by untreated celiac women might be the cause of reduced discomfort tolerance, thus increasing the subjective perception of menopausal symptoms.

Use of telomerase to create bioengineered tissues.

PubMed

Shay, Jerry W; Wright, Woodring E

2005-12-01

Telomeres are repetitive DNA (TTAGGG) elements at the ends of chromosomes. Telomerase is a ribonucleoprotein complex that catalyzes the addition of telomeric sequences to the ends of chromosomes. The catalytic protein component of telomerase (hTERT) is expressed only in specific germ line cells, proliferative stem cells of renewal tissues, and cancer cells. The expression of hTERT in normal cells reconstitutes telomerase activity and circumvents the induction of senescence. Telomeres shorten with each cell division, eventually leading to senescence (aging), due to incomplete lagging DNA strand synthesis and end-processing events, and because telomerase activity is not detected in most somatic tissues. There are specific tissues and locations in which replicative senescence likely contributes to the decline in human physiological function with increased age and with chronic illnesses. While expressing hTERT in cells results in the maintenance of telomere length and greatly extended life span, blocking replicative aging systemically would be predicted to increase the potential for tumor formation. However, there are many situations in which the transient rejuvenation of cells could be beneficial. Ectopic expression of hTERT has been shown to immortalize human skin keratinocytes, dermal fibroblasts, muscle satellite (stem), and vascular endothelial, myometrial, retinal-pigmented, and breast epithelial cells. In addition, human bronchial, corneal and skin cells expressing hTERT can be used to form organotypic (3D) cultures (bioengineered tissues) that express differentiation-specific proteins, demonstrating that hTERT by itself does not alter normal physiology. The production of hTERT-engineered tissues offers the possibility of producing tissues to treat a variety of chronic diseases and age-related medical conditions that are due to telomere-based replicative senescence.

Genetic Signatures of Exceptional Longevity in Humans

PubMed Central

Sebastiani, Paola; Solovieff, Nadia; DeWan, Andrew T.; Walsh, Kyle M.; Puca, Annibale; Hartley, Stephen W.; Melista, Efthymia; Andersen, Stacy; Dworkis, Daniel A.; Wilk, Jemma B.; Myers, Richard H.; Steinberg, Martin H.; Montano, Monty; Baldwin, Clinton T.; Hoh, Josephine; Perls, Thomas T.

2012-01-01

Like most complex phenotypes, exceptional longevity is thought to reflect a combined influence of environmental (e.g., lifestyle choices, where we live) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity in 801 centenarians (median age at death 104 years) and 914 genetically matched healthy controls. Using these data, we built a genetic model that includes 281 single nucleotide polymorphisms (SNPs) and discriminated between cases and controls of the discovery set with 89% sensitivity and specificity, and with 58% specificity and 60% sensitivity in an independent cohort of 341 controls and 253 genetically matched nonagenarians and centenarians (median age 100 years). Consistent with the hypothesis that the genetic contribution is largest with the oldest ages, the sensitivity of the model increased in the independent cohort with older and older ages (71% to classify subjects with an age at death>102 and 85% to classify subjects with an age at death>105). For further validation, we applied the model to an additional, unmatched 60 centenarians (median age 107 years) resulting in 78% sensitivity, and 2863 unmatched controls with 61% specificity. The 281 SNPs include the SNP rs2075650 in TOMM40/APOE that reached irrefutable genome wide significance (posterior probability of association = 1) and replicated in the independent cohort. Removal of this SNP from the model reduced the accuracy by only 1%. Further in-silico analysis suggests that 90% of centenarians can be grouped into clusters characterized by different “genetic signatures” of varying predictive values for exceptional longevity. The correlation between 3 signatures and 3 different life spans was replicated in the combined replication sets. The different signatures may help dissect this complex phenotype into sub-phenotypes of exceptional longevity. PMID:22279548

Electromagnetic field therapy delays cellular senescence and death by enhancement of the heat shock response.

PubMed

Perez, Felipe P; Zhou, Ximing; Morisaki, Jorge; Jurivich, Donald

2008-04-01

Hormesis may result when mild repetitive stress increases cellular defense against diverse injuries. This process may also extend in vitro cellular proliferative life span as well as delay and reverse some of the age-dependent changes in both replicative and non-replicative cells. This study evaluated the potential hormetic effect of non-thermal repetitive electromagnetic field shock (REMFS) and its impact on cellular aging and mortality in primary human T lymphocytes and fibroblast cell lines. Unlike previous reports employing electromagnetic radiation, this study used a long wave length, low energy, and non-thermal REMFS (50MHz/0.5W) for various therapeutic regimens. The primary outcomes examined were age-dependent morphological changes in cells over time, cellular death prevention, and stimulation of the heat shock response. REMFS achieved several biological effects that modified the aging process. REMFS extended the total number of population doublings of mouse fibroblasts and contributed to youthful morphology of cells near their replicative lifespan. REMFS also enhanced cellular defenses of human T cells as reflected in lower cell mortality when compared to non-treated T cells. To determine the mechanism of REMFS-induced effects, analysis of the cellular heat shock response revealed Hsp90 release from the heat shock transcription factor (HSF1). Furthermore, REMFS increased HSF1 phosphorylation, enhanced HSF1-DNA binding, and improved Hsp70 expression relative to non-REMFS-treated cells. These results show that non-thermal REMFS activates an anti-aging hormetic effect as well as reduces cell mortality during lethal stress. Because the REMFS configuration employed in this study can potentially be applied to whole body therapy, prospects for translating these data into clinical interventions for Alzheimer's disease and other degenerative conditions with aging are discussed.

Extreme longevity in a deep-sea vestimentiferan tubeworm and its implications for the evolution of life history strategies

NASA Astrophysics Data System (ADS)

Durkin, Alanna; Fisher, Charles R.; Cordes, Erik E.

2017-08-01

The deep sea is home to many species that have longer life spans than their shallow-water counterparts. This trend is primarily related to the decline in metabolic rates with temperature as depth increases. However, at bathyal depths, the cold-seep vestimentiferan tubeworm species Lamellibrachia luymesi and Seepiophila jonesi reach extremely old ages beyond what is predicted by the simple scaling of life span with body size and temperature. Here, we use individual-based models based on in situ growth rates to show that another species of cold-seep tubeworm found in the Gulf of Mexico, Escarpia laminata, also has an extraordinarily long life span, regularly achieving ages of 100-200 years with some individuals older than 300 years. The distribution of results from individual simulations as well as whole population simulations involving mortality and recruitment rates support these age estimates. The low 0.67% mortality rate measurements from collected populations of E. laminata are similar to mortality rates in L. luymesi and S. jonesi and play a role in evolution of the long life span of cold-seep tubeworms. These results support longevity theory, which states that in the absence of extrinsic mortality threats, natural selection will select for individuals that senesce slower and reproduce continually into their old age.

Pomegranate Juice Enhances Healthy Lifespan in Drosophila melanogaster: An Exploratory Study

PubMed Central

Balasubramani, Subramani Paranthaman; Mohan, Jayaram; Chatterjee, Arunita; Patnaik, Esha; Kukkupuni, Subrahmanya Kumar; Nongthomba, Upendra; Venkatasubramanian, Padmavathy

2014-01-01

Exploring innovative ways to ensure healthy aging 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 human beings. PMID:25566518

Health span approximates life span among many supercentenarians: compression of morbidity at the approximate limit of life span.

PubMed

Andersen, Stacy L; Sebastiani, Paola; Dworkis, Daniel A; Feldman, Lori; Perls, Thomas T

2012-04-01

We analyze the relationship between age of survival, morbidity, and disability among centenarians (age 100-104 years), semisupercentenarians (age 105-109 years), and supercentenarians (age 110-119 years). One hundred and four supercentenarians, 430 semisupercentenarians, 884 centenarians, 343 nonagenarians, and 436 controls were prospectively followed for an average of 3 years (range 0-13 years). The older the age group, generally, the later the onset of diseases, such as cancer, cardiovascular disease, dementia, and stroke, as well as of cognitive and functional decline. The hazard ratios for these individual diseases became progressively less with older and older age, and the relative period of time spent with disease was lower with increasing age group. We observed a progressive delay in the age of onset of physical and cognitive function impairment, age-related diseases, and overall morbidity with increasing age. As the limit of human life span was effectively approached with supercentenarians, compression of morbidity was generally observed.

Health Span Approximates Life Span Among Many Supercentenarians: Compression of Morbidity at the Approximate Limit of Life Span

PubMed Central

Andersen, Stacy L.; Sebastiani, Paola; Dworkis, Daniel A.; Feldman, Lori

2012-01-01

We analyze the relationship between age of survival, morbidity, and disability among centenarians (age 100–104 years), semisupercentenarians (age 105–109 years), and supercentenarians (age 110–119 years). One hundred and four supercentenarians, 430 semisupercentenarians, 884 centenarians, 343 nonagenarians, and 436 controls were prospectively followed for an average of 3 years (range 0–13 years). The older the age group, generally, the later the onset of diseases, such as cancer, cardiovascular disease, dementia, and stroke, as well as of cognitive and functional decline. The hazard ratios for these individual diseases became progressively less with older and older age, and the relative period of time spent with disease was lower with increasing age group. We observed a progressive delay in the age of onset of physical and cognitive function impairment, age-related diseases, and overall morbidity with increasing age. As the limit of human life span was effectively approached with supercentenarians, compression of morbidity was generally observed. PMID:22219514

SINGLE STRAND-CONTAINING REPLICATING MOLECULES OF CIRCULAR MITOCHONDRIAL DNA

PubMed Central

Wolstenholme, David R.; Koike, Katsuro; Cochran-Fouts, Patricia

1973-01-01

Mitochondrial DNAs (mtDNAs) from Chang rat solid hepatomas and Novikoff rat ascites hepatomas were examined in the electron microscope after preparation by the aqueous and by the formamide protein monolayer techniques. MtDNAs from both tumors were found to include double-forked circular molecules with a form and size suggesting they were replicative intermediates. These molecules were of two classes. In molecules of one class, all three segments were apparently totally double stranded. Molecules of the second class were distinguished by the fact that one of the segments spanning the region between the forks in which replication had occurred (the daughter segments) was either totally single stranded, or contained a single-stranded region associated with one of the forks. Daughter segments of both totally double-stranded and single strand-containing replicating molecules varied in length from about 3 to about 80% of the circular contour length of the molecule. Similar classes of replicating molecules were found in mtDNA from regenerating rat liver and chick embryos, indicating them to be normal intermediates in the replication of mtDNA All of the mtDNAs examined included partially single-stranded simple (nonforked) circular molecules. A possible scheme for the replication of mtDNA is presented, based on the different molecular forms observed PMID:4345165

Psychosocial stressors and the short life spans of legendary jazz musicians.

PubMed

Patalano, F

2000-04-01

Mean age at death of 168 legendary jazz musicians and 100 renowned classical musicians were compared to examine whether psychosocial stressors such as severe substance abuse, haphazard working conditions, lack of acceptance of jazz as an art form in the United States, marital and family discord, and a vagabond life style may have contributed to shortened life spans for the jazz musicians. Analysis indicated that the jazz musicians died at an earlier age (57.2 yr.) than the classical musicians (73.3 yr.).

Engineering a lunar photolithoautotroph to thrive on the moon - life or simulacrum?

NASA Astrophysics Data System (ADS)

Ellery, A. A.

2018-07-01

Recent work in developing self-replicating machines has approached the problem as an engineering problem, using engineering materials and methods to implement an engineering analogue of a hitherto uniquely biological function. The question is - can anything be learned that might be relevant to an astrobiological context in which the problem is to determine the general form of biology independent of the Earth. Compared with other non-terrestrial biology disciplines, engineered life is more demanding. Engineering a self-replicating machine tackles real environments unlike artificial life which avoids the problem of physical instantiation altogether by examining software models. Engineering a self-replicating machine is also more demanding than synthetic biology as no library of functional components exists. Everything must be constructed de novo. Biological systems already have the capacity to self-replicate but no engineered machine has yet been constructed with the same ability - this is our primary goal. On the basis of the von Neumann analysis of self-replication, self-replication is a by-product of universal construction capability - a universal constructor is a machine that can construct anything (in a functional sense) given the appropriate instructions (DNA/RNA), energy (ATP) and materials (food). In the biological cell, the universal construction mechanism is the ribosome. The ribosome is a biological assembly line for constructing proteins while DNA constitutes a design specification. For a photoautotroph, the energy source is ambient and the food is inorganic. We submit that engineering a self-replicating machine opens up new areas of astrobiology to be explored in the limits of life.

Changes in Acoustic Characteristics of the Voice across the Life Span: Measures from Individuals 4-93 Years of Age

ERIC Educational Resources Information Center

Stathopoulos, Elaine T.; Huber, Jessica E.; Sussman, Joan E.

2011-01-01

Purpose: The purpose of the present investigation was to examine acoustic voice changes across the life span. Previous voice production investigations used small numbers of participants, had limited age ranges, and produced contradictory results. Method: Voice recordings were made from 192 male and female participants 4-93 years of age. Acoustic…

Modeling Life-Span Growth Curves of Cognition Using Longitudinal Data with Multiple Samples and Changing Scales of Measurement

ERIC Educational Resources Information Center

McArdle, John J.; Grimm, Kevin J.; Hamagami, Fumiaki; Bowles, Ryan P.; Meredith, William

2009-01-01

The authors use multiple-sample longitudinal data from different test batteries to examine propositions about changes in constructs over the life span. The data come from 3 classic studies on intellectual abilities in which, in combination, 441 persons were repeatedly measured as many as 16 times over 70 years. They measured cognitive constructs…

The Use of Digital Technologies across the Adult Life Span in Distance Education

ERIC Educational Resources Information Center

Jelfs, Anne; Richardson, John T. E.

2013-01-01

In June 2010, a survey was carried out to explore access to digital technology, attitudes to digital technology and approaches to studying across the adult life span in students taking courses with the UK Open University. In total, 7000 people were surveyed, of whom more than 4000 responded. Nearly all these students had access to a computer and…

Auditory Environment across the Life Span of Cochlear Implant Users: Insights from Data Logging

ERIC Educational Resources Information Center

Busch, Tobias; Vanpoucke, Filiep; van Wieringen, Astrid

2017-01-01

Purpose: We describe the natural auditory environment of people with cochlear implants (CIs), how it changes across the life span, and how it varies between individuals. Method: We performed a retrospective cross-sectional analysis of Cochlear Nucleus 6 CI sound-processor data logs. The logs were obtained from 1,501 people with CIs (ages 0-96…

The Development of Attentional Networks: Cross-Sectional Findings from a Life Span Sample

ERIC Educational Resources Information Center

Waszak, Florian; Li, Shu-Chen; Hommel, Bernhard

2010-01-01

Using a population-based sample of 263 individuals ranging from 6 to 89 years of age, we investigated the gains and losses in the abilities to (a) use exogenous cues to shift attention covertly and (b) ignore conflicting information across the life span. The participants' ability to shift visual attention was tested by a typical Posner-type…

Life-Span Development of Visual Working Memory: When Is Feature Binding Difficult?

ERIC Educational Resources Information Center

Cowan, Nelson; Naveh-Benjamin, Moshe; Kilb, Angela; Saults, J. Scott

2006-01-01

We asked whether the ability to keep in working memory the binding between a visual object and its spatial location changes with development across the life span more than memory for item information. Paired arrays of colored squares were identical or differed in the color of one square, and in the latter case, the changed color was unique on…

Gains and Losses in Creative Personality as Perceived by Adults across the Life Span

ERIC Educational Resources Information Center

Hui, Anna N. N.; Yeung, Dannii Y.; Sue-Chan, Christina; Chan, Kara; Hui, Desmond C. K.; Cheng, Sheung-Tak

2014-01-01

In this study, we used a life span model to study the subjective perception of creative personality (CP) in emerging, young, middle-aged, and older Hong Kong Chinese adults. We also asked participants to estimate the approximate age by which people develop and lose CP across adulthood. We expected an interesting interplay between internalized age…

Extending the Human Life Span: An Exploratory Study of Pro- and Anti-Longevity Attitudes

ERIC Educational Resources Information Center

Kogan, Nathan; Tucker, Jennifer; Porter, Matthew

2011-01-01

Successful efforts by biologists to substantially increase the life span of non-human animals has raised the possibility of extrapolation to humans, which in turn has given rise to bioethical argumentation, pro and con. The present study converts these arguments into pro- and anti-longevity items on a questionnaire and examines the structure and…

Attitudes Toward Death Across the Life Span.

ERIC Educational Resources Information Center

Maiden, Robert; Walker, Gail

To understand the change and development of people's attitudes toward death over the life span, a 62-item attitude questionnaire on death and dying was administered to 90 adults. Participants included five females and five males in each of nine age categories: 18-20, 20-24, 25-29, 30-34, 35-39, 40-49, 50-59, 60-64, and 65 or older. Participants…

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

PubMed Central

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

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

PubMed

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.

Structure, replication efficiency and fragility of yeast ARS elements.

PubMed

Dhar, Manoj K; Sehgal, Shelly; Kaul, Sanjana

2012-05-01

DNA replication in eukaryotes initiates at specific sites known as origins of replication, or replicators. These replication origins occur throughout the genome, though the propensity of their occurrence depends on the type of organism. In eukaryotes, zones of initiation of replication spanning from about 100 to 50,000 base pairs have been reported. The characteristics of eukaryotic replication origins are best understood in the budding yeast Saccharomyces cerevisiae, where some autonomously replicating sequences, or ARS elements, confer origin activity. ARS elements are short DNA sequences of a few hundred base pairs, identified by their efficiency at initiating a replication event when cloned in a plasmid. ARS elements, although structurally diverse, maintain a basic structure composed of three domains, A, B and C. Domain A is comprised of a consensus sequence designated ACS (ARS consensus sequence), while the B domain has the DNA unwinding element and the C domain is important for DNA-protein interactions. Although there are ∼400 ARS elements in the yeast genome, not all of them are active origins of replication. Different groups within the genus Saccharomyces have ARS elements as components of replication origin. The present paper provides a comprehensive review of various aspects of ARSs, starting from their structural conservation to sequence thermodynamics. All significant and conserved functional sequence motifs within different types of ARS elements have been extensively described. Issues like silencing at ARSs, their inherent fragility and factors governing their replication efficiency have also been addressed. Progress in understanding crucial components associated with the replication machinery and timing at these ARS elements is discussed in the section entitled "The replicon revisited". Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Marker chromosome genomic structure and temporal origin implicate a chromoanasynthesis event in a family with pleiotropic psychiatric phenotypes.

PubMed

Grochowski, Christopher M; Gu, Shen; Yuan, Bo; Tcw, Julia; Brennand, Kristen J; Sebat, Jonathan; Malhotra, Dheeraj; McCarthy, Shane; Rudolph, Uwe; Lindstrand, Anna; Chong, Zechen; Levy, Deborah L; Lupski, James R; Carvalho, Claudia M B

2018-04-25

Small supernumerary marker chromosomes (sSMC) are chromosomal fragments difficult to characterize genomically. Here, we detail a proband with schizoaffective disorder and a mother with bipolar disorder with psychotic features who present with a marker chromosome that segregates with disease. We explored the architecture of this marker and investigated its temporal origin. Array comparative genomic hybridization (aCGH) analysis revealed three duplications and three triplications that spanned the short arm of chromosome 9, suggestive of a chromoanasynthesis-like event. Segregation of marker genotypes, phased using sSMC mosaicism in the mother, provided evidence that it was generated during a germline-level event in the proband's maternal grandmother. Whole-genome sequencing (WGS) was performed to resolve the structure and junctions of the chromosomal fragments, revealing further complexities. While structural variations have been previously associated with neuropsychiatric disorders and marker chromosomes, here we detail the precise architecture, human life-cycle genesis, and propose a DNA replicative/repair mechanism underlying formation. © 2018 Wiley Periodicals, Inc.

Fusion, fission, and transport control asymmetric inheritance of mitochondria and protein aggregates

PubMed Central

Böckler, Stefan; Chelius, Xenia; Hock, Nadine; Weiss, Matthias

2017-01-01

Partitioning of cell organelles and cytoplasmic components determines the fate of daughter cells upon asymmetric division. We studied the role of mitochondria in this process using budding yeast as a model. Anterograde mitochondrial transport is mediated by the myosin motor, Myo2. A genetic screen revealed an unexpected interaction of MYO2 and genes required for mitochondrial fusion. Genetic analyses, live-cell microscopy, and simulations in silico showed that fused mitochondria become critical for inheritance and transport across the bud neck in myo2 mutants. Similarly, fused mitochondria are essential for retention in the mother when bud-directed transport is enforced. Inheritance of a less than critical mitochondrial quantity causes a severe decline of replicative life span of daughter cells. Myo2-dependent mitochondrial distribution also is critical for the capture of heat stress–induced cytosolic protein aggregates and their retention in the mother cell. Together, these data suggest that coordination of mitochondrial transport, fusion, and fission is critical for asymmetric division and rejuvenation of daughter cells. PMID:28615194

Sharing the cell's bounty - organelle inheritance in yeast.

PubMed

Knoblach, Barbara; Rachubinski, Richard A

2015-02-15

Eukaryotic cells replicate and partition their organelles between the mother cell and the daughter cell at cytokinesis. Polarized cells, notably the budding yeast Saccharomyces cerevisiae, are well suited for the study of organelle inheritance, as they facilitate an experimental dissection of organelle transport and retention processes. Much progress has been made in defining the molecular players involved in organelle partitioning in yeast. Each organelle uses a distinct set of factors - motor, anchor and adaptor proteins - that ensures its inheritance by future generations of cells. We propose that all organelles, regardless of origin or copy number, are partitioned by the same fundamental mechanism involving division and segregation. Thus, the mother cell keeps, and the daughter cell receives, their fair and equitable share of organelles. This mechanism of partitioning moreover facilitates the segregation of organelle fragments that are not functionally equivalent. In this Commentary, we describe how this principle of organelle population control affects peroxisomes and other organelles, and outline its implications for yeast life span and rejuvenation. © 2015. Published by The Company of Biologists Ltd.

Nicotinamide riboside kinase structures reveal new pathways to NAD+.

PubMed

Tempel, Wolfram; Rabeh, Wael M; Bogan, Katrina L; Belenky, Peter; Wojcik, Marzena; Seidle, Heather F; Nedyalkova, Lyudmila; Yang, Tianle; Sauve, Anthony A; Park, Hee-Won; Brenner, Charles

2007-10-02

The eukaryotic nicotinamide riboside kinase (Nrk) pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to nicotinamide adenine dinucleotide (NAD+) by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize the distinctive carboxamide group of nicotinamide riboside. Indeed, nicotinic acid riboside is a specific substrate of human Nrk enzymes and is utilized in yeast in a novel biosynthetic pathway that depends on Nrk and NAD+ synthetase. Additionally, nicotinic acid riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage. Thus, crystal structures of Nrk1 led to the identification of new pathways to NAD+.

Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network.

PubMed

McConnell, Michael J; Moran, John V; Abyzov, Alexej; Akbarian, Schahram; Bae, Taejeong; Cortes-Ciriano, Isidro; Erwin, Jennifer A; Fasching, Liana; Flasch, Diane A; Freed, Donald; Ganz, Javier; Jaffe, Andrew E; Kwan, Kenneth Y; Kwon, Minseok; Lodato, Michael A; Mills, Ryan E; Paquola, Apua C M; Rodin, Rachel E; Rosenbluh, Chaggai; Sestan, Nenad; Sherman, Maxwell A; Shin, Joo Heon; Song, Saera; Straub, Richard E; Thorpe, Jeremy; Weinberger, Daniel R; Urban, Alexander E; Zhou, Bo; Gage, Fred H; Lehner, Thomas; Senthil, Geetha; Walsh, Christopher A; Chess, Andrew; Courchesne, Eric; Gleeson, Joseph G; Kidd, Jeffrey M; Park, Peter J; Pevsner, Jonathan; Vaccarino, Flora M

2017-04-28

Neuropsychiatric disorders have a complex genetic architecture. Human genetic population-based studies have identified numerous heritable sequence and structural genomic variants associated with susceptibility to neuropsychiatric disease. However, these germline variants do not fully account for disease risk. During brain development, progenitor cells undergo billions of cell divisions to generate the ~80 billion neurons in the brain. The failure to accurately repair DNA damage arising during replication, transcription, and cellular metabolism amid this dramatic cellular expansion can lead to somatic mutations. Somatic mutations that alter subsets of neuronal transcriptomes and proteomes can, in turn, affect cell proliferation and survival and lead to neurodevelopmental disorders. The long life span of individual neurons and the direct relationship between neural circuits and behavior suggest that somatic mutations in small populations of neurons can significantly affect individual neurodevelopment. The Brain Somatic Mosaicism Network has been founded to study somatic mosaicism both in neurotypical human brains and in the context of complex neuropsychiatric disorders. Copyright © 2017, American Association for the Advancement of Science.

DNA replication events during larval silk gland development in the silkworm, Bombyx mori.

PubMed

Zhang, Chun-Dong; Li, Fang-Fang; Chen, Xiang-Yun; Huang, Mao-Hua; Zhang, Jun; Cui, Hongjuan; Pan, Min-Hui; Lu, Cheng

2012-07-01

The silk gland is an important organ in silkworm as it synthesizes silk proteins and is critical to spinning. The genomic DNA content of silk gland cells dramatically increases 200-400 thousand times for the larval life span through the process of endomitosis. Using in vitro culture, DNA synthesis was measured using BrdU labeling during the larval molt and intermolt periods. We found that the cell cycle of endomitosis was activated during the intermolt and was inhibited during the molt phase. The anterior silk gland, middle silk gland, and posterior silk gland cells asynchronously exit the endomitotic cycle after day 6 in 5th instar larvae, which correlated with the reduced expression of the cell cycle-related cdt1, pcna, cyclin E, cdk2 and cdk1 mRNAs in the wandering phase. Additional starvation had no effect on the initiation of silk gland DNA synthesis of the freshly ecdysed larvae. Copyright © 2012 Elsevier Ltd. All rights reserved.

Life-span perspective of personality in dementia.

PubMed

Kolanowski, A M; Whall, A L

1996-01-01

To propose an alternative view of personality change in dementia by presenting existing evidence for the continuity of personality. As the population continues to age, dementing illnesses will account for a greater proportion of morbidity and mortality; the care of these people will have a significant effect on the health care system. Life-span perspective of personality continuity. SCOPE METHOD: Review of current literature on personality in dementia using Medline, 1980-1994; CINAHL, 1990-1994; and Psych Lit., 1980-1994. Although there are systematic shifts in personality with dementia, individuals tend to maintain their unique pattern of premorbid personality traits. The personalities of dementia patients seem to reflect adaptive patterns that served them in the past. Use of a life-span perspective can enhance individualized care for demented patients and advance theory development.

Demography of Genotypes: Failure of the Limited Life-Span Paradigm in Drosophila melanogaster

NASA Astrophysics Data System (ADS)

Curtsinger, James W.; Fukui, Hidenori H.; Townsend, David R.; Vaupel, James W.

1992-10-01

Experimental systems that are amenable to genetic manipulation can be used to address fundamental questions about genetic and nongenetic determinants of longevity. Analysis of large cohorts of ten genotypes of Drosophila melanogaster raised under conditions that favored extended survival has revealed variation between genotypes in both the slope and location of age-specific mortality curves. More detailed examination of a single genotype showed that the mortality trajectory was best fit by a two-stage Gompertz model, with no age-specific increase in mortality rates beyond 30 days after emergence. These results are contrary to the limited life-span paradigm, which postulates well-defined, genotype-specific limits on life-span and brief periods of intense and rapidly accelerating mortality rates at the oldest ages.

Large-scale replication study reveals a limit on probabilistic prediction in language comprehension.

PubMed

Nieuwland, Mante S; Politzer-Ahles, Stephen; Heyselaar, Evelien; Segaert, Katrien; Darley, Emily; Kazanina, Nina; Von Grebmer Zu Wolfsthurn, Sarah; Bartolozzi, Federica; Kogan, Vita; Ito, Aine; Mézière, Diane; Barr, Dale J; Rousselet, Guillaume A; Ferguson, Heather J; Busch-Moreno, Simon; Fu, Xiao; Tuomainen, Jyrki; Kulakova, Eugenia; Husband, E Matthew; Donaldson, David I; Kohút, Zdenko; Rueschemeyer, Shirley-Ann; Huettig, Falk

2018-04-03

Do people routinely pre-activate the meaning and even the phonological form of upcoming words? The most acclaimed evidence for phonological prediction comes from a 2005 Nature Neuroscience publication by DeLong, Urbach and Kutas, who observed a graded modulation of electrical brain potentials (N400) to nouns and preceding articles by the probability that people use a word to continue the sentence fragment ('cloze'). In our direct replication study spanning 9 laboratories ( N =334), pre-registered replication-analyses and exploratory Bayes factor analyses successfully replicated the noun-results but, crucially, not the article-results. Pre-registered single-trial analyses also yielded a statistically significant effect for the nouns but not the articles. Exploratory Bayesian single-trial analyses showed that the article-effect may be non-zero but is likely far smaller than originally reported and too small to observe without very large sample sizes. Our results do not support the view that readers routinely pre-activate the phonological form of predictable words. © 2018, Nieuwland et al.

Large-scale replication study reveals a limit on probabilistic prediction in language comprehension

PubMed Central

Politzer-Ahles, Stephen; Heyselaar, Evelien; Segaert, Katrien; Darley, Emily; Kazanina, Nina; Von Grebmer Zu Wolfsthurn, Sarah; Bartolozzi, Federica; Kogan, Vita; Ito, Aine; Mézière, Diane; Barr, Dale J; Rousselet, Guillaume A; Ferguson, Heather J; Busch-Moreno, Simon; Fu, Xiao; Tuomainen, Jyrki; Kulakova, Eugenia; Husband, E Matthew; Donaldson, David I; Kohút, Zdenko; Rueschemeyer, Shirley-Ann; Huettig, Falk

2018-01-01

Do people routinely pre-activate the meaning and even the phonological form of upcoming words? The most acclaimed evidence for phonological prediction comes from a 2005 Nature Neuroscience publication by DeLong, Urbach and Kutas, who observed a graded modulation of electrical brain potentials (N400) to nouns and preceding articles by the probability that people use a word to continue the sentence fragment (‘cloze’). In our direct replication study spanning 9 laboratories (N=334), pre-registered replication-analyses and exploratory Bayes factor analyses successfully replicated the noun-results but, crucially, not the article-results. Pre-registered single-trial analyses also yielded a statistically significant effect for the nouns but not the articles. Exploratory Bayesian single-trial analyses showed that the article-effect may be non-zero but is likely far smaller than originally reported and too small to observe without very large sample sizes. Our results do not support the view that readers routinely pre-activate the phonological form of predictable words. PMID:29631695

Microscopic Observation of Self-Propagation of Calcifying Nanoparticles (Nanobacteria)

NASA Technical Reports Server (NTRS)

Mathew, Grace; McKay, David S.; Ciftcioglu, Neva

2007-01-01

Biologists typically define living organisms as carbon and water-based cellular forms with :self-replication" as the fundamental trait of the life process. However, this standard dictionary definition of life does not help scientists to categorize self-replicators like viruses, prions, proteons and artificial life. CNP also named nanobacteria were discovered in early 1990s as about 100 nanometer-sized bacteria-like particles with unique apatite mineral-shells around them, and found to be associated with pathological-calcification related diseases. Although CNP have been isolated and cultured from mammalian blood and diseased calcified tissues, and their biomineralizing properties well established, their biological nature and self-replicating capability have always been severely challenged. The terms "self-replication", "self-assembly" or "self-propagation" have been widely used for all systems including nanomachines, crystals, computer viruses and memes. In a simple taxonomy, all biological and non-biological "self replicators", have been classified into "living" or "nonliving" based on the properties of the systems and the amount of support they require to self-replicate. To enhance our understanding about self-replicating nature of CNP, we have investigated their growth in specific culture conditions using conventional inverted light microscope and BioStation IM, Nikon s latest time-lapse imaging system. Their morphological structure was examined using scanning (SEM) and transmission (TEM) electron microscopy. This present study, in conjunction with previous findings of metabolic activity, antibiotic sensitivity, antibody specificity, morphological aspects and infectivity, all concomitantly validate CNP as living self-replicators.

A unique life history among tetrapods: An annual chameleon living mostly as an egg

PubMed Central

Karsten, Kristopher B.; Andriamandimbiarisoa, Laza N.; Fox, Stanley F.; Raxworthy, Christopher J.

2008-01-01

The ≈28,300 species of tetrapods (four-limbed vertebrates) almost exclusively have perennial life spans. Here, we report the discovery of a remarkable annual tetrapod from the arid southwest of Madagascar: the chameleon Furcifer labordi, with a posthatching life span of just 4–5 months. At the start of the active season (November), an age cohort of hatchlings emerges; larger juveniles or adults are not present. These hatchlings grow rapidly, reach sexual maturity in less than 2 months, and reproduce in January–February. After reproduction, senescence appears, and the active season concludes with population-wide adult death. Consequently, during the dry season, the entire population is represented by developing eggs that incubate for 8–9 months before synchronously hatching at the onset of the following rainy season. Remarkably, this chameleon spends more of its short annual life cycle inside the egg than outside of it. Our review of tetrapod longevity (>1,700 species) finds no others with such a short life span. These findings suggest that the notorious rapid death of chameleons in captivity may, for some species, actually represent the natural adult life span. Consequently, a new appraisal may be warranted concerning the viability of chameleon breeding programs, which could have special significance for species of conservation concern. Additionally, because F. labordi is closely related to other perennial species, this chameleon group may prove also to be especially well suited for comparative studies that focus on life history evolution and the ecological, genetic, and/or hormonal determinants of aging, longevity, and senescence. PMID:18591659

A unique life history among tetrapods: an annual chameleon living mostly as an egg.

PubMed

Karsten, Kristopher B; Andriamandimbiarisoa, Laza N; Fox, Stanley F; Raxworthy, Christopher J

2008-07-01

The approximately 28,300 species of tetrapods (four-limbed vertebrates) almost exclusively have perennial life spans. Here, we report the discovery of a remarkable annual tetrapod from the arid southwest of Madagascar: the chameleon Furcifer labordi, with a posthatching life span of just 4-5 months. At the start of the active season (November), an age cohort of hatchlings emerges; larger juveniles or adults are not present. These hatchlings grow rapidly, reach sexual maturity in less than 2 months, and reproduce in January-February. After reproduction, senescence appears, and the active season concludes with population-wide adult death. Consequently, during the dry season, the entire population is represented by developing eggs that incubate for 8-9 months before synchronously hatching at the onset of the following rainy season. Remarkably, this chameleon spends more of its short annual life cycle inside the egg than outside of it. Our review of tetrapod longevity (>1,700 species) finds no others with such a short life span. These findings suggest that the notorious rapid death of chameleons in captivity may, for some species, actually represent the natural adult life span. Consequently, a new appraisal may be warranted concerning the viability of chameleon breeding programs, which could have special significance for species of conservation concern. Additionally, because F. labordi is closely related to other perennial species, this chameleon group may prove also to be especially well suited for comparative studies that focus on life history evolution and the ecological, genetic, and/or hormonal determinants of aging, longevity, and senescence.

Drosophila melanogaster as a model system of aluminum toxicity and aging.

PubMed

Kijak, Ewelina; Rosato, Ezio; Knapczyk, Katarzyna; Pyza, Elżbieta

2014-04-01

The aim of this study was to investigate the toxic effects of aluminum (Al) on the model organism-Drosophila melanogaster. The study is especially concerned with the effects of aluminum on the fruit fly's development, life span, and circadian rhythm in rest and activity. Flies were exposed to aluminum in concentrations from 40 to 280 mg/kg in rearing media or the flies were raised on control medium. Moreover, the life span of insects exposed to aluminum containing 40, 120, or 240 mg/kg of Al in the medium, only during their larval development, during the whole life cycle and only in their adult life was tested. To check if aluminum and aging cause changes in D. melanogaster behavior, the locomotor activity of flies at different ages was recorded. Results showed that aluminum is toxic in concentrations above 160 mg/kg in the rearing medium. Depending on Al concentration and time of exposure, the life span of the flies was shortened. At intermediate concentrations (120 mg/kg), however, Al had a stimulating effect on males increasing their life span and level of locomotor activity. At higher concentration the aluminum exposure increased or decreased the level of locomotor activity of D. melanogaster depending on age of flies. In addition, in the oldest insects reared on aluminum supplemented media and in mid-aged flies reared on the highest concentration of Al the daily rhythm of activity was disrupted. © 2013 Institute of Zoology, Chinese Academy of Sciences.

Quantifying the Structure of Free Association Networks across the Life Span

ERIC Educational Resources Information Center

Dubossarsky, Haim; De Deyne, Simon; Hills, Thomas T.

2017-01-01

We investigate how the mental lexicon changes over the life span using free association data from over 8,000 individuals, ranging from 10 to 84 years of age, with more than 400 cue words per age group. Using network analysis, with words as nodes and edges defined by the strength of shared associations, we find that associative networks evolve in a…

Self-Esteem Development across the Life Span: A Longitudinal Study with a Large Sample from Germany

ERIC Educational Resources Information Center

Orth, Ulrich; Maes, Jürgen; Schmitt, Manfred

2015-01-01

The authors examined the development of self-esteem across the life span. Data came from a German longitudinal study with 3 assessments across 4 years of a sample of 2,509 individuals ages 14 to 89 years. The self-esteem measure used showed strong measurement invariance across assessments and birth cohorts. Latent growth curve analyses indicated…

Delayed accumulation of intestinal coliform bacteria enhances life span and stress resistance in Caenorhabditis elegans fed respiratory deficient E. coli.

PubMed

Gomez, Fernando; Monsalve, Gabriela C; Tse, Vincent; Saiki, Ryoichi; Weng, Emily; Lee, Laura; Srinivasan, Chandra; Frand, Alison R; Clarke, Catherine F

2012-12-20

Studies with the nematode model Caenorhabditis elegans have identified conserved biochemical pathways that act to modulate life span. Life span can also be influenced by the composition of the intestinal microbiome, and C. elegans life span can be dramatically influenced by its diet of Escherichia coli. Although C. elegans is typically fed the standard OP50 strain of E. coli, nematodes fed E. coli strains rendered respiratory deficient, either due to a lack coenzyme Q or the absence of ATP synthase, show significant life span extension. Here we explore the mechanisms accounting for the enhanced nematode life span in response to these diets. The intestinal load of E. coli was monitored by determination of worm-associated colony forming units (cfu/worm or coliform counts) as a function of age. The presence of GFP-expressing E. coli in the worm intestine was also monitored by fluorescence microscopy. Worms fed the standard OP50 E. coli strain have high cfu and GFP-labeled bacteria in their guts at the L4 larval stage, and show saturated coliform counts by day five of adulthood. In contrast, nematodes fed diets of respiratory deficient E. coli lacking coenzyme Q lived significantly longer and failed to accumulate bacteria within the lumen at early ages. Animals fed bacteria deficient in complex V showed intermediate coliform numbers and were not quite as long-lived. The results indicate that respiratory deficient Q-less E. coli are effectively degraded in the early adult worm, either at the pharynx or within the intestine, and do not accumulate in the intestinal tract until day ten of adulthood. The findings of this study suggest that the nematodes fed the respiratory deficient E. coli diet live longer because the delay in bacterial colonization of the gut subjects the worms to less stress compared to worms fed the OP50 E. coli diet. This work suggests that bacterial respiration can act as a virulence factor, influencing the ability of bacteria to colonize and subsequently harm the animal host. Respiratory deficient bacteria may pose a useful model for probing probiotic relationships within the gut microbiome in higher organisms.

Causes and consequences of variation in conifer leaf life-span

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reich, P.B.; Koike, T.; Gower, S.T.

1995-07-01

Species with mutually supporting traits, such as high N{sub mass}, SLA, and A{sub mass}, and short leaf life-span, tend to inhabit either generally resource-rich environments or spatial and/or temporal microhabitats that are resource-rich in otherwise more limited habitats (e.g., {open_quotes}precipitation{close_quotes} ephemerals in warm deserts or spring ephemerals in the understory of temperate deciduous forests). In contrast, species with long leaf life-span often support foliage with low SLA, N{sub mass}, and A{sub mass}, and often grow in low-temperature limited, dry, and/or nutrient-poor environments. The contrast between evergreen and deciduous species, and the implications that emerge from such comparisons, can be consideredmore » a paradigm of modern ecological theory. However, based on the results of Reich et al. (1992) and Gower et al. (1993), coniferous species with foliage that persists for 9-10 years are likely to assimilate and allocate carbon and nutrients differently than other evergreen conifers that retain foliage for 2-3 years. Thus, attempts to contrast ecophysiological or ecosystem characteristics of evergreen versus deciduous life forms may be misleading, and pronounced differences among evergreen conifers may be ignored. Clearly, the deciduous-evergreen contrast, although useful in several ways, should be viewed from the broader perspective of a gradient in leaf life-span.« less

Ageing in a eusocial insect: molecular and physiological characteristics of life span plasticity in the honey bee

PubMed Central

Münch, D.; Amdam, G. V.; Wolschin, F.

2008-01-01

Summary Commonly held views assume that ageing, or senescence, represents an inevitable, passive, and random decline in function that is strongly linked to chronological age. In recent years, genetic intervention of life span regulating pathways, for example, in Drosophila as well as case studies in non-classical animal models, have provided compelling evidence to challenge these views. Rather than comprehensively revisiting studies on the established genetic model systems of ageing, we here focus on an alternative model organism with a wild type (unselected genotype) characterized by a unique diversity in longevity – the honey bee. Honey bee (Apis mellifera) life span varies from a few weeks to more than 2 years. This plasticity is largely controlled by environmental factors. Thereby, although individuals are closely related genetically, distinct life histories can emerge as a function of social environmental change. Another remarkable feature of the honey bee is the occurrence of reverted behavioural ontogeny in the worker (female helper) caste. This behavioural peculiarity is associated with alterations in somatic maintenance functions that are indicative of reverted senescence. Thus, although intraspecific variation in organismal life span is not uncommon, the honey bee holds great promise for gaining insights into regulatory pathways that can shape the time-course of ageing by delaying, halting or even reversing processes of senescence. These aspects provide the setting of our review. We will highlight comparative findings from Drosophila melanogaster and Caenorhabditis elegans in particular, and focus on knowledge spanning from molecular- to behavioural-senescence to elucidate how the honey bee can contribute to novel insights into regulatory mechanisms that underlie plasticity and robustness or irreversibility in ageing. PMID:18728759

Ageing in a eusocial insect: molecular and physiological characteristics of life span plasticity in the honey bee.

PubMed

Münch, D; Amdam, G V; Wolschin, F

2008-01-01

Commonly held views assume that ageing, or senescence, represents an inevitable, passive, and random decline in function that is strongly linked to chronological age. In recent years, genetic intervention of life span regulating pathways, for example, in Drosophila as well as case studies in non-classical animal models, have provided compelling evidence to challenge these views.Rather than comprehensively revisiting studies on the established genetic model systems of ageing, we here focus on an alternative model organism with a wild type (unselected genotype) characterized by a unique diversity in longevity - the honey bee.Honey bee (Apis mellifera) life span varies from a few weeks to more than 2 years. This plasticity is largely controlled by environmental factors. Thereby, although individuals are closely related genetically, distinct life histories can emerge as a function of social environmental change.Another remarkable feature of the honey bee is the occurrence of reverted behavioural ontogeny in the worker (female helper) caste. This behavioural peculiarity is associated with alterations in somatic maintenance functions that are indicative of reverted senescence. Thus, although intraspecific variation in organismal life span is not uncommon, the honey bee holds great promise for gaining insights into regulatory pathways that can shape the time-course of ageing by delaying, halting or even reversing processes of senescence. These aspects provide the setting of our review.We will highlight comparative findings from Drosophila melanogaster and Caenorhabditis elegans in particular, and focus on knowledge spanning from molecular- to behavioural-senescence to elucidate how the honey bee can contribute to novel insights into regulatory mechanisms that underlie plasticity and robustness or irreversibility in ageing.

Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change.

PubMed

Storsve, Andreas B; Fjell, Anders M; Tamnes, Christian K; Westlye, Lars T; Overbye, Knut; Aasland, Hilde W; Walhovd, Kristine B

2014-06-18

Human cortical thickness and surface area are genetically independent, emerge through different neurobiological events during development, and are sensitive to different clinical conditions. However, the relationship between changes in the two over time is unknown. Additionally, longitudinal studies have almost invariably been restricted to older adults, precluding the delineation of adult life span trajectories of change in cortical structure. In this longitudinal study, we investigated changes in cortical thickness, surface area, and volume after an average interval of 3.6 years in 207 well screened healthy adults aged 23-87 years. We hypothesized that the relationships among metrics are dynamic across the life span, that the primary contributor to cortical volume reductions in aging is cortical thinning, and that magnitude of change varies with age and region. Changes over time were seen in cortical area (mean annual percentage change [APC], -0.19), thickness (APC, -0.35), and volume (APC, -0.51) in most regions. Volume changes were primarily explained by changes in thickness rather than area. A negative relationship between change in thickness and surface area was found across several regions, where more thinning was associated with less decrease in area, and vice versa. Accelerating changes with increasing age was seen in temporal and occipital cortices. In contrast, decelerating changes were seen in prefrontal and anterior cingulate cortices. In conclusion, a dynamic relationship between cortical thickness and surface area changes exists throughout the adult life span. The mixture of accelerating and decelerating changes further demonstrates the importance of studying these metrics across the entire adult life span. Copyright © 2014 the authors 0270-6474/14/348488-11$15.00/0.

Inducible knockdown of pregnancy-associated plasma protein-A gene expression in adult female mice extends life span.

PubMed

Bale, Laurie K; West, Sally A; Conover, Cheryl A

2017-08-01

Pregnancy-associated plasma protein-A (PAPP-A) knockout (KO) mice, generated through homologous recombination in embryonic stem cells, have a significantly increased lifespan compared to wild-type littermates. However, it is unknown whether this longevity advantage would pertain to PAPP-A gene deletion in adult animals. In the present study, we used tamoxifen (Tam)-inducible Cre recombinase-mediated excision of the floxed PAPP-A (fPAPP-A) gene in mice at 5 months of age. fPAPP-A mice, which were either positive (pos) or negative (neg) for Tam-Cre, received Tam treatment with quarterly boosters. Only female mice could be used with this experimental design. fPAPP-A/neg and fPAPP-A/pos mice had similar weights at the start of the experiment and showed equivalent weight gain. We found that fPAPP-A/pos mice had a significant extension of life span (P = 0.005). The median life span was increased by 21% for fPAPP-A/pos compared to fPAPP-A/neg mice. Analysis of mortality in life span quartiles indicated that the proportion of deaths of fPAPP-A/pos mice were lower than fPAPP-A/neg mice at young adult ages (P = 0.002 for 601-800 days) and higher than fPAPP-A/neg mice at older ages (P = 0.004 for >1000 days). Thus, survival curves and age-specific mortality indicate that female mice with knockdown of PAPP-A gene expression as adults have an extended healthy life span. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Dietary supplementation with Lovaza and krill oil shortens the life span of long-lived F1 mice.

PubMed

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

2014-06-01

Marine oils rich in ω-3 polyunsaturated fatty acids have been recommended as a preventive treatment for patients at risk for cardiovascular diseases. These oils also are the third most consumed dietary supplement in the USA. However, evidence for their health benefits is equivocal. We tested the daily, isocaloric administration of krill oil (1.17 g oil/kg diet) and Lovaza (Omacor; 4.40 g/kg diet), a pharmaceutical grade fish oil, beginning at 12 months of age, on the life span and mortality-related pathologies of long-lived, male, B6C3F1 mice. The oils were incorporated into the chemically defined American Institute of Nutrition (AIN)-93 M diet. An equivalent volume of soybean oil was removed. Krill oil was 3 % and Lovaza 11 % of the oil in the diets. When their effects were analyzed together, the marine oils significantly shortened life span by 6.6 % (P = 0.0321; log-rank test) relative to controls. Individually, Lovaza and krill oil non-significantly shortened median life span by 9.8 and 4.7 %, respectively. Lovaza increased the number of enlarged seminal vesicles (7.1-fold). Lovaza and krill oil significantly increased lung tumors (4.1- and 8.2-fold) and hemorrhagic diathesis (3.9- and 3.1-fold). Analysis of serum from treated mice found that Lovaza slightly increased blood urea nitrogen, while krill oil modestly increased bilirubin, triglycerides, and blood glucose levels. Taken together, the results do not support the idea that the consumption of isolated ω-3 fatty acid-rich oils will increase the life span or health of initially healthy individuals.

A Modelling Study for Predicting Life of Downhole Tubes Considering Service Environmental Parameters and Stress

PubMed Central

Zhao, Tianliang; Liu, Zhiyong; Du, Cuiwei; Hu, Jianpeng; Li, Xiaogang

2016-01-01

A modelling effort was made to try to predict the life of downhole tubes or casings, synthetically considering the effect of service influencing factors on corrosion rate. Based on the discussed corrosion mechanism and corrosion processes of downhole tubes, a mathematic model was established. For downhole tubes, the influencing factors are environmental parameters and stress, which vary with service duration. Stress and the environmental parameters including water content, partial pressure of H2S and CO2, pH value, total pressure and temperature, were considered to be time-dependent. Based on the model, life-span of an L80 downhole tube in oilfield Halfaya, an oilfield in Iraq, was predicted. The results show that life-span of the L80 downhole tube in Halfaya is 247 months (approximately 20 years) under initial stress of 0.1 yield strength and 641 months (approximately 53 years) under no initial stress, which indicates that an initial stress of 0.1 yield strength will reduce the life-span by more than half. PMID:28773872

Contributions to Engineering Models of Human-Computer Interaction. Volume 1.

DTIC Science & Technology

1988-05-06

for those readers wishing to replicate my results. Volume II is on file in the Carnegie-Mellon library and is available upon request from the author...a 50 mieec 10 10 10 10 170 170 170 Moo, sf 4 170 Mooc Figure 4-20: Schedule chart of the perception-wait algorithm for the detection span task

Empowering Teachers with Low-Intensity Strategies to Support Instruction: Self-Monitoring in an Elementary Resource Classroom

ERIC Educational Resources Information Center

Ennis, Robin Parks; Lane, Kathleen Lynne; Oakes, Wendy Peia

2018-01-01

Self-monitoring is a low-intensity strategy teachers can use to support instruction in classrooms across the grade span in various instructional settings and content areas. This study extended the knowledge base by examining the effectiveness of self-monitoring through a systematic replication with three students with specific learning…

Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides

PubMed Central

Artan, Murat; Jeong, Dae-Eun; Lee, Dongyeop; Kim, Young-Il; Son, Heehwa G.; Husain, Zahabiya; Kim, Jinmahn; Altintas, Ozlem; Kim, Kyuhyung; Alcedo, Joy; Lee, Seung-Jae V.

2016-01-01

Environmental fluctuations influence organismal aging by affecting various regulatory systems. One such system involves sensory neurons, which affect life span in many species. However, how sensory neurons coordinate organismal aging in response to changes in environmental signals remains elusive. Here, we found that a subset of sensory neurons shortens Caenorhabditis elegans’ life span by differentially regulating the expression of a specific insulin-like peptide (ILP), INS-6. Notably, treatment with food-derived cues or optogenetic activation of sensory neurons significantly increases ins-6 expression and decreases life span. INS-6 in turn relays the longevity signals to nonneuronal tissues by decreasing the activity of the transcription factor DAF-16/FOXO. Together, our study delineates a mechanism through which environmental sensory cues regulate aging rates by modulating the activities of specific sensory neurons and ILPs. PMID:27125673

The contribution to immediate serial recall of rehearsal, search speed, access to lexical memory, and phonological coding: an investigation at the construct level.

PubMed

Tehan, Gerald; Fogarty, Gerard; Ryan, Katherine

2004-07-01

Rehearsal speed has traditionally been seen to be the prime determinant of individual differences in memory span. Recent studies, in the main using young children as the participant population, have suggested other contributors to span performance. In the present research, we used structural equation modeling to explore, at the construct level, individual differences in immediate serial recall with respect to rehearsal, search, phonological coding, and speed of access to lexical memory. We replicated standard short-term phenomena; we showed that the variables that influence children's span performance influence adult performance in the same way; and we showed that speed of access to lexical memory and facility with phonological codes appear to be more potent sources of individual differences in immediate memory than is either rehearsal speed or search factors.

MINIGENOMES, TRANSCRIPTION AND REPLICATION COMPETENT VIRUS-LIKE PARTICLES AND BEYOND: REVERSE GENETICS SYSTEMS FOR FILOVIRUSES AND OTHER NEGATIVE STRANDED HEMORRHAGIC FEVER VIRUSES

PubMed Central

Hoenen, Thomas; Groseth, Allison; de Kok-Mercado, Fabian; Kuhn, Jens H.; Wahl-Jensen, Victoria

2012-01-01

Reverse-genetics systems are powerful tools enabling researchers to study the replication cycle of RNA viruses, including filoviruses and other hemorrhagic fever viruses, as well as to discover new antivirals. They include full-length clone systems as well as a number of life cycle modeling systems. Full-length clone systems allow for the generation of infectious, recombinant viruses, and thus are an important tool for studying the virus replication cycle in its entirety. In contrast, life cycle modeling systems such as minigenome and transcription and replication competent virus-like particle systems can be used to simulate and dissect parts of the virus life cycle outside of containment facilities. Minigenome systems are used to model viral genome replication and transcription, whereas transcription and replication competent virus-like particle systems also model morphogenesis and budding as well as infection of target cells. As such, these modeling systems have tremendous potential to further the discovery and screening of new antivirals targeting hemorrhagic fever viruses. This review provides an overview of currently established reverse genetics systems for hemorrhagic fever-causing negative-sense RNA viruses, with a particular emphasis on filoviruses, and the potential application of these systems for antiviral research. PMID:21699921

Reconstructing life history of hominids and humans.

PubMed

Crews, Douglas E; Gerber, Linda M

2003-06-01

Aspects of life history, such as processes and timing of development, age at maturation, and life span are consistently associated with one another across the animal kingdom. Species that develop rapidly tend to mature and reproduce early, have many offspring, and exhibit shorter life spans (r-selection) than those that develop slowly, have extended periods of premature growth, mature later in life, reproduce later and less frequently, have few offspring and/or single births, and exhibit extended life spans (K-selection). In general, primates are among the most K-selected of species. A suite of highly derived life history traits characterizes humans. Among these are physically immature neonates, slowed somatic development both in utero and post-natally, late attainment of reproductive maturity and first birth, and extended post-mature survival. Exactly when, why, and through what types of evolutionary interactions this suite arose is currently the subject of much conjecture and debate. Humankind's biocultural adaptations have helped to structure human life history evolution in unique ways not seen in other animal species. Among all species, life history traits may respond rapidly to alterations in selective pressures through hormonal processes. Selective pressures on life history likely varied widely among hominids and humans over their evolutionary history. This suggests that current patterns of human growth, development, maturation, reproduction, and post-mature survival may be of recent genesis, rather then long-standing adaptations. Thus, life history patterns observed among contemporary human and chimpanzee populations may provide little insight to those that existed earlier in hominid/human evolution.

Severe Acute Respiratory Syndrome Coronavirus Replication Is Severely Impaired by MG132 due to Proteasome-Independent Inhibition of M-Calpain

PubMed Central

Schneider, Martha; Ackermann, Kerstin; Stuart, Melissa; Wex, Claudia; Protzer, Ulrike; Schätzl, Hermann M.

2012-01-01

The ubiquitin-proteasome system (UPS) is involved in the replication of a broad range of viruses. Since replication of the murine hepatitis virus (MHV) is impaired upon proteasomal inhibition, the relevance of the UPS for the replication of the severe acute respiratory syndrome coronavirus (SARS-CoV) was investigated in this study. We demonstrate that the proteasomal inhibitor MG132 strongly inhibits SARS-CoV replication by interfering with early steps of the viral life cycle. Surprisingly, other proteasomal inhibitors (e.g., lactacystin and bortezomib) only marginally affected viral replication, indicating that the effect of MG132 is independent of proteasomal impairment. Induction of autophagy by MG132 treatment was excluded from playing a role, and no changes in SARS-CoV titers were observed during infection of wild-type or autophagy-deficient ATG5−/− mouse embryonic fibroblasts overexpressing the human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2). Since MG132 also inhibits the cysteine protease m-calpain, we addressed the role of calpains in the early SARS-CoV life cycle using calpain inhibitors III (MDL28170) and VI (SJA6017). In fact, m-calpain inhibition with MDL28170 resulted in an even more pronounced inhibition of SARS-CoV replication (>7 orders of magnitude) than did MG132. Additional m-calpain knockdown experiments confirmed the dependence of SARS-CoV replication on the activity of the cysteine protease m-calpain. Taken together, we provide strong experimental evidence that SARS-CoV has unique replication requirements which are independent of functional UPS or autophagy pathways compared to other coronaviruses. Additionally, this work highlights an important role for m-calpain during early steps of the SARS-CoV life cycle. PMID:22787216

Fragmentation, Fusion, and Genetic Homogeneity in a Calcareous Sponge (Porifera, Calcarea).

PubMed

Padua, André; Leocorny, Pedro; Custódio, Márcio Reis; Klautau, Michelle

2016-06-01

Sessile marine invertebrates living on hard substrata usually present strategies such as size variations, longer life spans, fragmentation and fusion to occupy and compete for space. Calcareous sponges are usually small and short-lived, and some species are known to undergo frequent fragmentation and fusion events. However, whether fusion occurs only between genetically identical individuals remains unclear. We investigated the occurrence of chimaeras in the calcareous sponge Clathrina aurea by following the dynamics of fragmentation and fusion of 66 individuals in the field for up to 18 months and determined size variations and the life span of each individual. Microsatellites were used to determine whether fusion events occur among genetically different individuals. Growth and shrinkage of individuals were frequently observed, showing that size cannot be associated with age in C. aurea. The life span of the species ranged from 1 to 16 months (mean: 4.7 months). Short life spans and variable growth rates have been observed in other species of the class Calcarea. Fragmentation and fusion events were observed, but fusion events always occurred between genetically identical individuals, as has been suggested by graft experiments in adult Demospongiae and other Calcarea. These results suggest that at least C. aurea adults may have some mechanism to avoid chimaerism. © 2016 Wiley Periodicals, Inc.

Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice.

PubMed

Arriola Apelo, Sebastian I; Pumper, Cassidy P; Baar, Emma L; Cummings, Nicole E; Lamming, Dudley W

2016-07-01

Inhibition of the mTOR (mechanistic target of rapamycin) signaling pathway by the FDA-approved drug rapamycin promotes life span in numerous model organisms and delays age-related disease in mice. However, the utilization of rapamycin as a therapy for age-related diseases will likely prove challenging due to the serious metabolic and immunological side effects of rapamycin in humans. We recently identified an intermittent rapamycin treatment regimen-2mg/kg administered every 5 days-with a reduced impact on glucose homeostasis and the immune system as compared with chronic treatment; however, the ability of this regimen to extend life span has not been determined. Here, we report for the first time that an intermittent rapamycin treatment regimen starting as late as 20 months of age can extend the life span of female C57BL/6J mice. Our work demonstrates that the anti-aging potential of rapamycin is separable from many of its negative side effects and suggests that carefully designed dosing regimens may permit the safer use of rapamycin and its analogs for the treatment of age-related diseases in humans. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Control of Viremia and Prevention of AIDS following Immunotherapy of SIV-Infected Macaques with Peptide-Pulsed Blood

PubMed Central

De Rose, Robert; Fernandez, Caroline S.; Smith, Miranda Z.; Batten, C. Jane; Alcântara, Sheilajen; Peut, Vivienne; Rollman, Erik; Loh, Liyen; Mason, Rosemarie D.; Wilson, Kim; Law, Matthew G.; Handley, Amanda J.; Kent, Stephen J.

2008-01-01

Effective immunotherapies for HIV are needed. Drug therapies are life-long with significant toxicities. Dendritic-cell based immunotherapy approaches are promising but impractical for widespread use. A simple immunotherapy, reinfusing fresh autologous blood cells exposed to overlapping SIV peptides for 1 hour ex vivo, was assessed for the control of SIVmac251 replication in 36 pigtail macaques. An initial set of four immunizations was administered under antiretroviral cover and a booster set of three immunizations administered 6 months later. Vaccinated animals were randomized to receive Gag peptides alone or peptides spanning all nine SIV proteins. High-level, SIV-specific CD4 and CD8 T-cell immunity was induced following immunization, both during antiretroviral cover and without. Virus levels were durably ∼10-fold lower for 1 year in immunized animals compared to controls, and a significant delay in AIDS-related mortality resulted. Broader immunity resulted following immunizations with peptides spanning all nine SIV proteins, but the responses to Gag were weaker in comparison to animals only immunized with Gag. No difference in viral outcome occurred in animals immunized with all SIV proteins compared to animals immunized against Gag alone. Peptide-pulsed blood cells are an immunogenic and effective immunotherapy in SIV-infected macaques. Our results suggest Gag alone is an effective antigen for T-cell immunotherapy. Fresh blood cells pulsed with overlapping Gag peptides is proceeding into trials in HIV-infected humans. PMID:18451982

In silico ribozyme evolution in a metabolically coupled RNA population.

PubMed

Könnyű, Balázs; Szilágyi, András; Czárán, Tamás

2015-05-27

The RNA World hypothesis offers a plausible bridge from no-life to life on prebiotic Earth, by assuming that RNA, the only known molecule type capable of playing genetic and catalytic roles at the same time, could have been the first evolvable entity on the evolutionary path to the first living cell. We have developed the Metabolically Coupled Replicator System (MCRS), a spatially explicit simulation modelling approach to prebiotic RNA-World evolution on mineral surfaces, in which we incorporate the most important experimental facts and theoretical considerations to comply with recent knowledge on RNA and prebiotic evolution. In this paper the MCRS model framework has been extended in order to investigate the dynamical and evolutionary consequences of adding an important physico-chemical detail, namely explicit replicator structure - nucleotide sequence and 2D folding calculated from thermodynamical criteria - and their possible mutational changes, to the assumptions of a previously less detailed toy model. For each mutable nucleotide sequence the corresponding 2D folded structure with minimum free energy is calculated, which in turn is used to determine the fitness components (degradation rate, replicability and metabolic enzyme activity) of the replicator. We show that the community of such replicators providing the monomer supply for their own replication by evolving metabolic enzyme activities features an improved propensity for stable coexistence and structural adaptation. These evolutionary advantages are due to the emergent uniformity of metabolic replicator fitnesses imposed on the community by local group selection and attained through replicator trait convergence, i.e., the tendency of replicator lengths, ribozyme activities and population sizes to become similar between the coevolving replicator species that are otherwise both structurally and functionally different. In the most general terms it is the surprisingly high extra viability of the metabolic replicator system that the present model adds to the MCRS concept of the origin of life. Surface-bound, metabolically coupled RNA replicators tend to evolve different, enzymatically active sites within thermodynamically stable secondary structures, and the system as a whole evolves towards the robust coexistence of a complete set of such ribozymes driving the metabolism producing monomers for their own replication.

Calcein represses human papillomavirus 16 E1-E2 mediated DNA replication via blocking their binding to the viral origin of replication.

PubMed

Das, Dipon; Smith, Nathan W; Wang, Xu; Richardson, Stacie L; Hartman, Matthew C T; Morgan, Iain M

2017-08-01

Human papillomaviruses are causative agents in several human diseases ranging from genital warts to ano-genital and oropharyngeal cancers. Currently only symptoms of HPV induced disease are treated; there are no antivirals available that directly target the viral life cycle. Previously, we determined that the cellular protein TopBP1 interacts with the HPV16 replication/transcription factor E2. This E2-TopBP1 interaction is essential for optimal E1-E2 DNA replication and for the viral life cycle. The drug calcein disrupts the interaction of TopBP1 with itself and other host proteins to promote cell death. Here we demonstrate that calcein blocks HPV16 E1-E2 DNA replication via blocking the viral replication complex forming at the origin of replication. This occurs at non-toxic levels of calcein and demonstrates specificity as it does not block the ability of E2 to regulate transcription. We propose that calcein or derivatives could be developed as an anti-HPV therapeutic. Copyright © 2017 Elsevier Inc. All rights reserved.

Shorter Life Span of Microorganisms and Plants as a Consequence of Shielded Magnetic Environment

NASA Astrophysics Data System (ADS)

Dobrota, C.; Piso, I. M.; Bathory, D.

The geomagnetic field is an essential environmental factor for life and health on this planet. In order to survey how magnetic fields affect the life span and the nitrogenase (an iron-sulphur enzyme) activity of Azotobacter chroococcum as well as the life span, the main organic synthesis and the water balance of plants (22 species), the biological tests were incubated under shielded magnetic field and also in normal geo-magnetic environment. The shielding level was about 10-6 of the terrestrial magnetic field.Life cycles of all organisms require the co-ordinated control of a complex set of interlocked physiological processes and metabolic pathways. Such processes are likely to be regulated by a large number of genes. Our researches suggest that the main point in biological structures, which seems to be affected by the low magnetic environment, is the water molecule. Magnetic field induces a molecular alignment. Under shielded conditions, unstructured water molecules with fewer hydrogen bonds, which are producing a more reactive environment, are occurring. As compared to control, the life span of both microorganisms and plants was shorter in shielded environment. A higher nitrogenase affinity for the substrate was recorded in normal geo-magnetic field compared to low magnetic field. The synthesis of carbohydrates, lipids, proteins and enzymes was modified under experimental conditions. The stomatal conductance was higher between 158 and 300% in shielded environment indicating an important water loss from the plant cells.Our results support the idea that the shielded magnetic environment induces different reactions depending on the time of exposure and on the main metabolic pathways of the cells.

Mechanisms by which HPV Induces a Replication Competent Environment in Differentiating Keratinocytes

PubMed Central

Moody, Cary A.

2017-01-01

Human papillomaviruses (HPV) are the causative agents of cervical cancer and are also associated with other genital malignancies, as well as an increasing number of head and neck cancers. HPVs have evolved their life cycle to contend with the different cell states found in the stratified epithelium. Initial infection and viral genome maintenance occurs in the proliferating basal cells of the stratified epithelium, where cellular replication machinery is abundant. However, the productive phase of the viral life cycle, including productive replication, late gene expression and virion production, occurs upon epithelial differentiation, in cells that normally exit the cell cycle. This review outlines how HPV interfaces with specific cellular signaling pathways and factors to provide a replication-competent environment in differentiating cells. PMID:28925973

Disentangling the mental health impact of childhood abuse and neglect: A replication and extension study in a Brazilian sample of high-risk youth.

PubMed

de Oliveira, Irismar Reis; Matos-Ragazzo, Ana Cristina; Zhang, Yuning; Vasconcelos, Nina Maia; Velasquez, Michella Lopes; Reis, Daniela; Ribeiro, Monica Gonçalves; da Rocha, Marina Monzani; Rosario, Maria Conceição; Stallard, Paul; Cecil, Charlotte A M

2018-06-01

Childhood maltreatment is a key predictor of mental health problems across the life span. Yet, how maltreatment types independently and jointly influence the risk for psychiatric problems remains unclear. The aim of the study was two-fold: first, to replicate recent findings regarding the impact of maltreatment types on youth psychiatric symptoms, based on a Brazilian sample of high-risk adolescents (n = 347; age range = 11-17 yrs), and second, to extend existing findings by examining whether this relationship is mediated by bullying victimization and/or perpetration. Measures included self-report ratings of childhood maltreatment and peer victimization, as well as multi-informant reports of internalizing and externalizing symptoms. Consistent with prior research, we found that: (i) maltreatment types often co-occurred; (ii) there was a linear association between number of maltreatment types experienced and symptom severity (i.e. cumulative effect); and (iii) emotional abuse emerged as the most consistent independent predictor of poor mental health across domains, raters, and gender. Additionally, this study extends previous findings by showing that the influence of maltreatment on psychiatric outcomes is partially mediated by peer victimization, but not by bullying perpetration. In conclusion, these findings expand our understanding of the heterogeneity in individual responses to maltreatment as well as highlighting emotional abuse as an important predictor of poor mental health. Copyright © 2018. Published by Elsevier Ltd.

Exome-wide Association Study Identifies CLEC3B Missense Variant p.S106G as Being Associated With Extreme Longevity in East Asian Populations

PubMed Central

Tanisawa, Kumpei; Arai, Yasumichi; Hirose, Nobuyoshi; Shimokata, Hiroshi; Yamada, Yoshiji; Kawai, Hisashi; Kojima, Motonaga; Obuchi, Shuichi; Hirano, Hirohiko; Yoshida, Hideyo; Suzuki, Hiroyuki; Fujiwara, Yoshinori; Ihara, Kazushige; Sugaya, Maki; Arai, Tomio; Mori, Seijiro; Sawabe, Motoji; Sato, Noriko; Muramatsu, Masaaki; Higuchi, Mitsuru; Liu, Yao-Wen; Kong, Qing-Peng

2017-01-01

Abstract Life span is a complex trait regulated by multiple genetic and environmental factors; however, the genetic determinants of extreme longevity have been largely unknown. To identify the functional coding variants associated with extreme longevity, we performed an exome-wide association study (EWAS) on a Japanese population by using an Illumina HumanExome Beadchip and a focused replication study on a Chinese population. The EWAS on two independent Japanese cohorts consisting of 530 nonagenarians/centenarians demonstrated that the G allele of CLEC3B missense variant p.S106G was associated with extreme longevity at the exome-wide level of significance (p = 2.33×10–7, odds ratio [OR] = 1.50). The CLEC3B gene encodes tetranectin, a protein implicated in the mineralization process in osteogenesis as well as in the prognosis and metastasis of cancer. The replication study consisting of 448 Chinese nonagenarians/centenarians showed that the G allele of CLEC3B p.S106G was also associated with extreme longevity (p = .027, OR = 1.51), and the p value of this variant reached 1.87×10–8 in the meta-analysis of Japanese and Chinese populations. In conclusion, the present study identified the CLEC3B p.S106G as a novel longevity-associated variant, raising the novel hypothesis that tetranectin, encoded by CLEC3B, plays a role in human longevity and aging. PMID:27154906

A peptide targeted against phosphoprotein and leader RNA interaction inhibits growth of Chandipura virus -- an emerging rhabdovirus.

PubMed

Roy, Arunava; Chakraborty, Prasenjit; Polley, Smarajit; Chattopadhyay, Dhrubajyoti; Roy, Siddhartha

2013-11-01

The fatal illness caused by Chandipura virus (CHPV), an emerging pathogen, presently lacks any therapeutic option. Previous research suggested that interaction between the virally encoded phosphoprotein (P) and the positive sense leader RNA (le-RNA) may play an important role in the viral lifecycle. In this report, we have identified a β-sheet/loop motif in the C-terminal domain of the CHPV P protein as essential for this interaction. A synthetic peptide encompassing this motif and spanning a continuous stretch of 36 amino acids (Pep208-243) was found to bind the le-RNA in vitro and inhibit CHPV growth in infected cells. Furthermore, a stretch of three amino acid residues at position 217-219 was identified as essential for this interaction, both in vitro and in infected cells. siRNA knockdown-rescue experiments demonstrated that these three amino acid residues are crucial for the leader RNA binding function of P protein in the CHPV life cycle. Mutations of these three amino acid residues render the peptide completely ineffective against CHPV. Effect of inhibition of phosphoprotein-leader RNA interaction on viral replication was assayed. Peptide Pep208-243 tagged with a cell penetrating peptide was found to inhibit CHPV replication as ascertained by real time RT-PCR. The specific inhibition of viral growth observed using this peptide suggests a new possibility for designing of anti-viral agents against Mononegavirale group of human viruses. Copyright © 2013. Published by Elsevier B.V.

Relationships of leaf dark respiration to leaf nitrogen, specific leaf area and leaf life-span: a test across biomes and functional groups

Treesearch

Peter B. Reich; Michael B. Walters; David S. Ellsworth; [and others; [Editor’s note: James M.. Vose is the SRS co-author for this publication.

1998-01-01

Based on prior evidence of coordinated multiple leaf trait scaling, the authors hypothesized that variation among species in leaf dark respiration rate (Rd) should scale with variation in traits such as leaf nitrogen (N), leaf life-span, specific leaf area (SLA), and net photosynthetic capacity (Amax). However, it is not known whether such scaling, if it exists, is...

[Effect of pineal peptide on parameters of the biological age and life span in mice].

PubMed

Anisimov, V N; Khavinson, V Kh; Zavarzina, N Iu; Zabezhinskiĭ, M A; Zimina, O A; Popovich, I G; Shtylik, A V; Arutiunian, A V; Oparina, T I; Prokopenko, V M

2001-01-01

Female CBA mice were injected with s.c. synthetic tetrapeptide Epithalon from a 6-month age until death. The drug failed to affect the body weight or food consumption, physical activity or behavioural parameters. However, it slowed down the age-related switching off of the estrus function, decreased body temperature, decelerated free redical processes, prolonged the mice life span with an accompanying drop in spontaneous tumour incidence.

Spatial abilities across the adult life span.

PubMed

Borella, Erika; Meneghetti, Chiara; Ronconi, Lucia; De Beni, Rossana

2014-02-01

The study investigates age-related effects across the adult life span on spatial abilities (testing subabilities based on a distinction between spatial visualization, mental rotation, and perspective taking) and spatial self-assessments. The sample consisted of 454 participants (223 women and 231 men) from 20 to 91 years of age. Results showed nonlinear age-related effects for spatial visualization and perspective taking but linear effects for mental rotation; few or no age-related effects were found for spatial self-assessments. Working memory accounted for only a small proportion of the variance in all spatial tasks and had no effect on spatial self-assessments. Overall, our findings suggest that the influence of age on spatial skills across the adult life span is considerable, but the effects of age change as a function of the spatial task considered, and the effect on spatial self-assessment is more marginal.

Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides.

PubMed

Artan, Murat; Jeong, Dae-Eun; Lee, Dongyeop; Kim, Young-Il; Son, Heehwa G; Husain, Zahabiya; Kim, Jinmahn; Altintas, Ozlem; Kim, Kyuhyung; Alcedo, Joy; Lee, Seung-Jae V

2016-05-01

Environmental fluctuations influence organismal aging by affecting various regulatory systems. One such system involves sensory neurons, which affect life span in many species. However, how sensory neurons coordinate organismal aging in response to changes in environmental signals remains elusive. Here, we found that a subset of sensory neurons shortens Caenorhabditis elegans' life span by differentially regulating the expression of a specific insulin-like peptide (ILP), INS-6. Notably, treatment with food-derived cues or optogenetic activation of sensory neurons significantly increases ins-6 expression and decreases life span. INS-6 in turn relays the longevity signals to nonneuronal tissues by decreasing the activity of the transcription factor DAF-16/FOXO. Together, our study delineates a mechanism through which environmental sensory cues regulate aging rates by modulating the activities of specific sensory neurons and ILPs. © 2016 Artan et al.; Published by Cold Spring Harbor Laboratory Press.

Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

PubMed Central

Koch, Karoline; Havermann, Susannah; Büchter, Christian

2014-01-01

Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research. PMID:24895670

Basic traits predict the prevalence of personality disorder across the life span: the example of psychopathy.

PubMed

Vachon, David D; Lynam, Donald R; Widiger, Thomas A; Miller, Joshua D; McCrae, Robert R; Costa, Paul T

2013-05-01

Personality disorders (PDs) may be better understood in terms of dimensions of general personality functioning rather than as discrete categorical conditions. Personality-trait descriptions of PDs are robust across methods and settings, and PD assessments based on trait measures show good construct validity. The study reported here extends research showing that basic traits (e.g., impulsiveness, warmth, straightforwardness, modesty, and deliberation) can re-create the epidemiological characteristics associated with PDs. Specifically, we used normative changes in absolute trait levels to simulate age-related differences in the prevalence of psychopathy in a forensic setting. Results demonstrated that trait information predicts the rate of decline for psychopathy over the life span; discriminates the decline of psychopathy from that of a similar disorder, antisocial PD; and accurately predicts the differential decline of subfactors of psychopathy. These findings suggest that basic traits provide a parsimonious account of PD prevalence across the life span.

daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans.

PubMed

Lin, K; Dorman, J B; Rodan, A; Kenyon, C

1997-11-14

The wild-type Caenorhabditis elegans nematode ages rapidly, undergoing development, senescence, and death in less than 3 weeks. In contrast, mutants with reduced activity of the gene daf-2, a homolog of the insulin and insulin-like growth factor receptors, age more slowly than normal and live more than twice as long. These mutants are active and fully fertile and have normal metabolic rates. The life-span extension caused by daf-2 mutations requires the activity of the gene daf-16. daf-16 appears to play a unique role in life-span regulation and encodes a member of the hepatocyte nuclear factor 3 (HNF-3)/forkhead family of transcriptional regulators. In humans, insulin down-regulates the expression of certain genes by antagonizing the activity of HNF-3, raising the possibility that aspects of this regulatory system have been conserved.

NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice.

PubMed

Zhang, Hongbo; Ryu, Dongryeol; Wu, Yibo; Gariani, Karim; Wang, Xu; Luan, Peiling; D'Amico, Davide; Ropelle, Eduardo R; Lutolf, Matthias P; Aebersold, Ruedi; Schoonjans, Kristina; Menzies, Keir J; Auwerx, Johan

2016-06-17

Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD(+) precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmd(mdx)/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD(+) may reprogram dysfunctional SCs and improve life span in mammals. Copyright © 2016, American Association for the Advancement of Science.

Quality of College Life (QCL) of Students: Further Validation of a Measure of Well-Being

ERIC Educational Resources Information Center

Sirgy, M. Joseph; Lee, Dong-Jin; Grzeskowiak, Stephan; Yu, Grace B.; Webb, Dave; El-Hasan, Karma; Vega, Jose Jesus Garcia; Ekici, Ahmet; Johar, J. S.; Krishen, Anjala; Kangal, Ayca; Swoboda, Bernhard; Claiborne, C. B.; Maggino, Filomena; Rahtz, Don; Canton, Alicia; Kuruuzum, Ayse

2010-01-01

This paper reports a study designed to further validate a measure of quality of college life (QCL) of university students (Sirgy, Grzeskowiak, Rahtz, "Soc Indic Res" 80(2), 343-360, 2007). Two studies were conducted: a replication study and an extension study. The replication study involved surveys of 10 different college campuses in different…

Partner preferences across the life span: online dating by older adults.

PubMed

Alterovitz, Sheyna Sears-Roberts; Mendelsohn, Gerald A

2009-06-01

Stereotypes of older adults as withdrawn or asexual fail to recognize that romantic relationships in later life are increasingly common. The authors analyzed 600 Internet personal ads from 4 age groups: 20-34, 40-54, 60-74, and 75+ years. Predictions from evolutionary theory held true in later life, when reproduction is no longer a concern. Across the life span, men sought physical attractiveness and offered status-related information more than women; women were more selective than men and sought status more than men. With age, men desired women increasingly younger than themselves, whereas women desired older men until ages 75 and over, when they sought men younger than themselves. (c) 2009 APA, all rights reserved.

Accumulation of linear mitochondrial DNA fragments in the nucleus shortens the chronological life span of yeast.

PubMed

Cheng, Xin; Ivessa, Andreas S

2012-10-01

Translocation of mitochondrial DNA (mtDNA) fragments to the nucleus and insertion of those fragments into nuclear DNA has been observed in several organisms ranging from yeast to plants and mammals. Disruption of specific nuclear genes by de novo insertions of mtDNA fragments has even been linked to the initiation of several human diseases. Recently, we demonstrated that baker's yeast strains with high rates of mtDNA fragments migrating to the nucleus (yme1-1 mutant) exhibit short chronological life spans (CLS). The yeast CLS is determined by the survival of non-dividing cell populations. Here, we show that lack of the non-homologous-end-joining enzyme DNA ligase IV (DNL4) can rescue the short CLS of the yme1-1 mutant. In fission yeast, DNA ligase IV has been shown to be required for the capture of mtDNA fragments during the repair of double-stranded DNA breaks in nuclear DNA. In further analyses using pulse field gel and 2D gel electrophoresis we demonstrate that linear mtDNA fragments with likely nuclear localization accumulate in the yme1-1 mutant. The accumulation of the linear mtDNA fragments in the yme1-1 mutant is suppressed when Dnl4 is absent. We propose that the linear nuclear mtDNA fragments accelerate the aging process in the yme1-1 mutant cells by possibly affecting nuclear processes including DNA replication, recombination, and repair as well as transcription of nuclear genes. We speculate further that Dnl4 protein has besides its function as a ligase also a role in DNA protection. Dnl4 protein may stabilize the linear mtDNA fragments in the nucleus by binding to their physical ends. In the absence of Dnl4 protein the linear fragments are therefore unprotected and possibly degraded by nuclear nucleases. Copyright © 2012 Elsevier GmbH. All rights reserved.

Balancing Life Roles to Achieve Career Happiness and Life Satisfaction.

ERIC Educational Resources Information Center

Peronne, Kristin Marie

2000-01-01

A study guided by Super's Life Span, Life Space approach included a survey of 119 women and 66 men about sacrifices made in life and work roles to achieve balance and satisfaction. Differences in sacrifices and satisfaction were related to the combination of life roles they occupied. (SK)

Life span and reproductive cost explain interspecific variation in the optimal onset of reproduction.

PubMed

Mourocq, Emeline; Bize, Pierre; Bouwhuis, Sandra; Bradley, Russell; Charmantier, Anne; de la Cruz, Carlos; Drobniak, Szymon M; Espie, Richard H M; Herényi, Márton; Hötker, Hermann; Krüger, Oliver; Marzluff, John; Møller, Anders P; Nakagawa, Shinichi; Phillips, Richard A; Radford, Andrew N; Roulin, Alexandre; Török, János; Valencia, Juliana; van de Pol, Martijn; Warkentin, Ian G; Winney, Isabel S; Wood, Andrew G; Griesser, Michael

2016-02-01

Fitness can be profoundly influenced by the age at first reproduction (AFR), but to date the AFR-fitness relationship only has been investigated intraspecifically. Here, we investigated the relationship between AFR and average lifetime reproductive success (LRS) across 34 bird species. We assessed differences in the deviation of the Optimal AFR (i.e., the species-specific AFR associated with the highest LRS) from the age at sexual maturity, considering potential effects of life history as well as social and ecological factors. Most individuals adopted the species-specific Optimal AFR and both the mean and Optimal AFR of species correlated positively with life span. Interspecific deviations of the Optimal AFR were associated with indices reflecting a change in LRS or survival as a function of AFR: a delayed AFR was beneficial in species where early AFR was associated with a decrease in subsequent survival or reproductive output. Overall, our results suggest that a delayed onset of reproduction beyond maturity is an optimal strategy explained by a long life span and costs of early reproduction. By providing the first empirical confirmations of key predictions of life-history theory across species, this study contributes to a better understanding of life-history evolution. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Self-esteem development across the life span: a longitudinal study with a large sample from Germany.

PubMed

Orth, Ulrich; Maes, Jürgen; Schmitt, Manfred

2015-02-01

The authors examined the development of self-esteem across the life span. Data came from a German longitudinal study with 3 assessments across 4 years of a sample of 2,509 individuals ages 14 to 89 years. The self-esteem measure used showed strong measurement invariance across assessments and birth cohorts. Latent growth curve analyses indicated that self-esteem follows a quadratic trajectory across the life span, increasing during adolescence, young adulthood, and middle adulthood, reaching a peak at age 60 years, and then declining in old age. No cohort effects on average levels of self-esteem or on the shape of the trajectory were found. Moreover, the trajectory did not differ across gender, level of education, or for individuals who had lived continuously in West versus East Germany (i.e., the 2 parts of Germany that had been separate states from 1949 to 1990). However, the results suggested that employment status, household income, and satisfaction in the domains of work, relationships, and health contribute to a more positive life span trajectory of self-esteem. The findings have significant implications, because they call attention to developmental stages in which individuals may be vulnerable because of low self-esteem (such as adolescence and old age) and to factors that predict successful versus problematic developmental trajectories. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Template Directed Replication Supports the Maintenance of the Metabolically Coupled Replicator System

NASA Astrophysics Data System (ADS)

Könnyű, Balázs; Czárán, Tamás

2015-06-01

The RNA World scenario of prebiotic chemical evolution is among the most plausible conceptual framework available today for modelling the origin of life. RNA offers genetic and catalytic (metabolic) functionality embodied in a single chemical entity, and a metabolically cooperating community of RNA molecules would constitute a viable infrabiological subsystem with a potential to evolve into proto-cellular life. Our Metabolically Coupled Replicator System (MCRS) model is a spatially explicit computer simulation implementation of the RNA-World scenario, in which replicable ribozymes cooperate in supplying each other with monomers for their own replication. MCRS has been repeatedly demonstrated to be viable and evolvable, with different versions of the model improved in depth (chemical detail of metabolism) or in extension (additional functions of RNA molecules). One of the dynamically relevant extensions of the MCRS approach to prebiotic RNA evolution is the explicit inclusion of template replication into its assumptions, which we have studied in the present version. We found that this modification has not changed the behaviour of the system in the qualitative sense, just the range of the parameter space which is optimal for the coexistence of metabolically cooperating replicators has shifted in terms of metabolite mobility. The system also remains resistant and tolerant to parasitic replicators.

Self-Enhancement of Hepatitis C Virus Replication by Promotion of Specific Sphingolipid Biosynthesis

PubMed Central

Hirata, Yuichi; Ikeda, Kazutaka; Sudoh, Masayuki; Tokunaga, Yuko; Suzuki, Akemi; Weng, Leiyun; Ohta, Masatoshi; Tobita, Yoshimi; Okano, Ken; Ozeki, Kazuhisa; Kawasaki, Kenichi; Tsukuda, Takuo; Katsume, Asao; Aoki, Yuko; Umehara, Takuya; Sekiguchi, Satoshi; Toyoda, Tetsuya; Shimotohno, Kunitada; Soga, Tomoyoshi; Nishijima, Masahiro; Taguchi, Ryo; Kohara, Michinori

2012-01-01

Lipids are key components in the viral life cycle that affect host-pathogen interactions. In this study, we investigated the effect of HCV infection on sphingolipid metabolism, especially on endogenous SM levels, and the relationship between HCV replication and endogenous SM molecular species. We demonstrated that HCV induces the expression of the genes (SGMS1 and 2) encoding human SM synthases 1 and 2. We observed associated increases of both total and individual sphingolipid molecular species, as assessed in human hepatocytes and in the detergent-resistant membrane (DRM) fraction in which HCV replicates. SGMS1 expression had a correlation with HCV replication. Inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase (SPT) inhibitor, NA808, suppressed HCV-RNA production while also interfering with sphingolipid metabolism. Further, we identified the SM molecular species that comprise the DRM fraction and demonstrated that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication. Our results reveal that HCV alters sphingolipid metabolism to promote viral replication, providing new insights into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle. PMID:22916015

Self-enhancement of hepatitis C virus replication by promotion of specific sphingolipid biosynthesis.

PubMed

Hirata, Yuichi; Ikeda, Kazutaka; Sudoh, Masayuki; Tokunaga, Yuko; Suzuki, Akemi; Weng, Leiyun; Ohta, Masatoshi; Tobita, Yoshimi; Okano, Ken; Ozeki, Kazuhisa; Kawasaki, Kenichi; Tsukuda, Takuo; Katsume, Asao; Aoki, Yuko; Umehara, Takuya; Sekiguchi, Satoshi; Toyoda, Tetsuya; Shimotohno, Kunitada; Soga, Tomoyoshi; Nishijima, Masahiro; Taguchi, Ryo; Kohara, Michinori

2012-01-01

Lipids are key components in the viral life cycle that affect host-pathogen interactions. In this study, we investigated the effect of HCV infection on sphingolipid metabolism, especially on endogenous SM levels, and the relationship between HCV replication and endogenous SM molecular species. We demonstrated that HCV induces the expression of the genes (SGMS1 and 2) encoding human SM synthases 1 and 2. We observed associated increases of both total and individual sphingolipid molecular species, as assessed in human hepatocytes and in the detergent-resistant membrane (DRM) fraction in which HCV replicates. SGMS1 expression had a correlation with HCV replication. Inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase (SPT) inhibitor, NA808, suppressed HCV-RNA production while also interfering with sphingolipid metabolism. Further, we identified the SM molecular species that comprise the DRM fraction and demonstrated that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication. Our results reveal that HCV alters sphingolipid metabolism to promote viral replication, providing new insights into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle.

The life span-prolonging effect of sirtuin-1 is mediated by autophagy.

PubMed

Morselli, Eugenia; Maiuri, Maria Chiara; Markaki, Maria; Megalou, Evgenia; Pasparaki, Angela; Palikaras, Konstantinos; Criollo, Alfredo; Galluzzi, Lorenzo; Malik, Shoaib Ahmad; Vitale, Ilio; Michaud, Mickael; Madeo, Frank; Tavernarakis, Nektarios; Kroemer, Guido

2010-01-01

The life span of various model organisms can be extended by caloric restriction as well as by autophagy-inducing pharmacological agents. Life span-prolonging effects have also been observed in yeast cells, nematodes and flies upon the overexpression of the deacetylase Sirtuin-1. Intrigued by these observations and by the established link between caloric restriction and Sirtuin-1 activation, we decided to investigate the putative implication of Sirtuin-1 in the response of human cancer cells and Caenorhabditis elegans to multiple triggers of autophagy. Our data indicate that the activation of Sirtuin-1 (by the pharmacological agent resveratrol and/or genetic means) per se ignites autophagy, and that Sirtuin-1 is required for the autophagic response to nutrient deprivation, in both human and nematode cells, but not for autophagy triggered by downstream signals such as the inhibition of mTOR or p53. Since the life spanextending effects of Sirtuin-1 activators are lost in autophagy-deficient C. elegans, our results suggest that caloric restriction and resveratrol extend longevity, at least in experimental settings, by activating autophagy.

Are viruses alive? The replicator paradigm sheds decisive light on an old but misguided question

PubMed Central

Koonin, Eugene V.; Starokadomskyy, Petro

2016-01-01

The question whether or not “viruses are alive” has caused considerable debate over many years. Yet, the question is effectively without substance because the answer depends entirely on the definition of life or the state of “being alive” that is bound to be arbitrary. In contrast, the status of viruses among biological entities is readily defined within the replicator paradigm. All biological replicators form a continuum along the selfishness-cooperativity axis, from the completely selfish to fully cooperative forms. Within this range, typical, lytic viruses represent the selfish extreme whereas temperate viruses and various mobile elements occupy positions closer to the middle of the range. Selfish replicators not only belong to the biological realm but are intrinsic to any evolving system of replicators. No such system can evolve without the emergence of parasites, and moreover, parasites drive the evolution of biological complexity at multiple levels. The history of life is a story of parasite-host coevolution that includes both the incessant arms race and various forms of cooperation. All organisms are communities of interacting, coevolving replicators of different classes. A complete theory of replicator coevolution remains to be developed, but it appears likely that not only the differentiation between selfish and cooperative replicators but the emergence of the entire range of replication strategies, from selfish to cooperative, is intrinsic to biological evolution. PMID:26965225

Protein domains connect cell cycle stimulation directly to initiation of DNA replication.

PubMed Central

Gjørup, O V; Rose, P E; Holman, P S; Bockus, B J; Schaffhausen, B S

1994-01-01

Polyoma large T antigen (LT) is the only viral gene product required for viral DNA replication. LT can be divided into two domains, one N-terminal (NT) spanning residues 1-260 and one C-terminal (CT) comprising approximately residues 264-785. NT is known to immortalize primary cells in a manner dependent on binding of pRB/p107. Here a CT construct comprising residues 264-785 was shown to have independent function in DNA replication. CT is entirely sufficient for driving viral DNA replication in vivo in growing mouse cells at a level approaching that of full-length LT. In contrast, CT is strikingly deficient for replication in serum-starved cells. However, this deficiency can be complemented by coexpression of NT. BrdUrd incorporation in transfected, starved cells showed that NT was sufficient for inducing S phase, suggesting a mechanism for complementation. By contrast, CT was unable to induce S phase when tested in the same assay. NT also promotes phosphorylation of sites in CT that are likely to be important for replication. Other DNA tumor virus gene products such as adenovirus E1A 12S and human papillomavirus 16 E7 could also complement CT for replication. Although NT, E1A 12S, and E7 all bind the retinoblastoma gene product (pRB) and p107, genetic analysis demonstrates an additional function, independent of that binding, is responsible for complementation. Images PMID:7991595

Spatio-temporal organization of replication in bacteria and eukaryotes (nucleoids and nuclei).

PubMed

Jackson, Dean; Wang, Xindan; Rudner, David Z

2012-08-01

Here we discuss the spatio-temporal organization of replication in eubacteria and eukaryotes. Although there are significant differences in how replication is organized in cells that contain nuclei from those that do not, you will see that organization of replication in all organisms is principally dictated by the structured arrangement of the chromosome. We will begin with how replication is organized in eubacteria with particular emphasis on three well studied model organisms. We will then discuss spatial and temporal organization of replication in eukaryotes highlighting the similarities and differences between these two domains of life.

Spatio-Temporal Organization of Replication in Bacteria and Eukaryotes (Nucleoids and Nuclei)

PubMed Central

Jackson, Dean; Wang, Xindan; Rudner, David Z.

2012-01-01

Here we discuss the spatio-temporal organization of replication in eubacteria and eukaryotes. Although there are significant differences in how replication is organized in cells that contain nuclei from those that do not, you will see that organization of replication in all organisms is principally dictated by the structured arrangement of the chromosome. We will begin with how replication is organized in eubacteria with particular emphasis on three well studied model organisms. We will then discuss spatial and temporal organization of replication in eukaryotes highlighting the similarities and differences between these two domains of life. PMID:22855726

Physical Performance Across the Adult Life Span: Correlates With Age and Physical Activity.

PubMed

Hall, Katherine S; Cohen, Harvey J; Pieper, Carl F; Fillenbaum, Gerda G; Kraus, William E; Huffman, Kim M; Cornish, Melissa A; Shiloh, Andrew; Flynn, Christy; Sloane, Richard; Newby, L Kristin; Morey, Miriam C

2017-04-01

A number of large-scale population studies have provided valuable information about physical performance in aged individuals; however, there is little information about trajectories of function and associations with age across the adult life span. We developed a mobility-focused physical performance screener designed to be appropriate for the adult life span. The physical performance battery includes measures of mobility, strength, endurance, and balance. Physical activity (PA) was assessed with accelerometry. We examined age-related trends in physical performance and PA, and the relationship between physical performance and PA across the age range (30-90+), by decade, in 775 participants enrolled in the study 2012-2014. Physical performance was worse with increasing age decade. Although men performed better than women across all ages, the decrement by age group was similar between genders. Worsening physical performance was observed as early as the fifth decade for chair stands and balance and in the sixth decade for gait speed and aerobic endurance. The number and strength of significant associations between physical performance and PA increased with greater age: the greatest number of significant associations was seen in the 60-79 age groups, with fewer reported in the 30-59 and 80-90+ age groups. More PA was associated with better physical function. These results emphasize the importance of a life span approach to studies of function and aging. This work points to the need for a physical performance screener that spans across adulthood as a clinical tool for identifying functional decline. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Deficiency mapping of quantitative trait loci affecting longevity in Drosophila melanogaster.

PubMed Central

Pasyukova, E G; Vieira, C; Mackay, T F

2000-01-01

In a previous study, sex-specific quantitative trait loci (QTL) affecting adult longevity were mapped by linkage to polymorphic roo transposable element markers, in a population of recombinant inbred lines derived from the Oregon and 2b strains of Drosophila melanogaster. Two life span QTL were each located on chromosomes 2 and 3, within sections 33E-46C and 65D-85F on the cytological map, respectively. We used quantitative deficiency complementation mapping to further resolve the locations of life span QTL within these regions. The Oregon and 2b strains were each crossed to 47 deficiencies spanning cytological regions 32F-44E and 64C-76B, and quantitative failure of the QTL alleles to complement the deficiencies was assessed. We initially detected a minimum of five and four QTL in the chromosome 2 and 3 regions, respectively, illustrating that multiple linked factors contribute to each QTL detected by recombination mapping. The QTL locations inferred from deficiency mapping did not generally correspond to those of candidate genes affecting oxidative and thermal stress or glucose metabolism. The chromosome 2 QTL in the 35B-E region was further resolved to a minimum of three tightly linked QTL, containing six genetically defined loci, 24 genes, and predicted genes that are positional candidates corresponding to life span QTL. This region was also associated with quantitative variation in life span in a sample of 10 genotypes collected from nature. Quantitative deficiency complementation is an efficient method for fine-scale QTL mapping in Drosophila and can be further improved by controlling the background genotype of the strains to be tested. PMID:11063689

Proteotoxicity and the contrasting effects of oxaloacetate and glycerol on Caenorhabditis elegans life span: a role for methylglyoxal?

PubMed

Hipkiss, Alan R

2010-10-01

Because accumulation of altered proteins is the most common biochemical symptom of aging, it is at least possible that such proteotoxicity may cause aging and influence life span. The life span of the nematode worm Caenorhabditis elegans is strongly influenced by changes in the intracellular concentration of methylglyoxal (MG), a putative source of much age-related proteotoxicity and organelle, cellular, and molecular dysfunction. Glycerol has recently been shown to shorten, whereas oxaloacetate has been found to extend, life span in C. elegans. It is suggested here that glycerol and oxaloacetate exert opposing effects on MG formation in C. elegans. It is proposed that, if not secreted by aquaporin, glycerol is converted to glycerol phosphate and then to dihydroxyacetone phosphate (DHAP) via a reaction requiring nicotinamide adenine dinucleotide (NAD(+)). This inhibits operation of the glycerol phosphate cycle in which DHAP is converted into glycerol phosphate, which concomitantly regenerates NAD(+) from NADH, thereby ensuring glycolytic oxidation of glyceraldehyde-3-phosphate (G3P). Because DHAP and G3P spontaneously decompose into MG, and NAD(+) is required for conversion of G3P into phosphoglycerate, the glycerol-induced increased DHAP formation and decreased NAD(+) availability will increase the potential for MG generation. In contrast, oxaloacetate may decrease MG generation by stimulating the operation of the malate-oxaloacetate shuttle, in which oxaloacetate is converted to malate, which regenerates NAD(+) from NADH. By the ensuing G3P oxidation, increased NAD(+) availability will decrease the potential for MG formation. It should be noted that mitochondria are involved in the operation of the above cycle/shuttles and that increased NAD(+) availability also stimulates those sirtuin activities that increase mitogenesis and mitochondrial activity via effects on signal transduction and gene expression, which frequently accompany dietary restriction-induced life span extension.

The Social Context of Managing Diabetes across the Life Span

PubMed Central

Wiebe, Deborah J.; Helgeson, Vicki; Berg, Cynthia A.

2016-01-01

Diabetes self-management is crucial to maintaining quality of life and preventing long-term complications, and occurs daily in the context of close interpersonal relationships. This article examines how social relationships are central to meeting the complex demands of managing type 1 and type 2 diabetes across the life span. The social context of diabetes management includes multiple resources, including family (parents, spouses), peers, romantic partners, and health care providers. We discuss how these social resources change across the life span, focusing on childhood and adolescence, emerging adulthood, and adulthood and aging. We review how diabetes both affects and is affected by key social relationships at each developmental period. Despite high variability in how the social context is conceptualized and measured across studies, findings converge on the characteristics of social relationships that facilitate or undermine diabetes management across the life span. These characteristics are consistent with both Interpersonal Theory and Self-Determination Theory, two organizing frameworks that we utilize to explore social behaviors that are related to diabetes management. Involvement and support from one’s social partners, particularly family members, is consistently associated with good diabetes outcomes when characterized by warmth, collaboration and acceptance. Under-involvement and interactions characterized by conflict and criticism are consistently associated with poor diabetes outcomes. Intrusive involvement that contains elements of social control may undermine diabetes management, particularly when it impinges on self-efficacy. Implications for future research directions and for interventions that promote the effective use of the social context to improve diabetes self-management are discussed. PMID:27690482

Production dynamics of intensively managed loblolly pine stands in the southern United States: a synthesis of seven long-term experiments

Treesearch

Eric J. Jokela; Philip M. Dougherty; Timothy A. Martin

2004-01-01

Results from seven long-term experiments in the southern US were summarized to understand production dynamics of intensively managed loblolly pine plantations. Replicated studies that spanned a wide range of soil and climatic conditions were established (North Carolina-NC; Georgia-GA (three sites); Florida-F%; Louisiana-LA; Oklahoma--OK). A11 experiments received some...

The Impact of Recent Federal Administrative Rules on Army Dental Care. Volume 1. A Cost Analysis of Bloodborne Pathogens: A Report of Consultation

DTIC Science & Technology

1992-12-31

procedure codes 9973 and 9974), and the unit cost to the Fort Sam Houston DENTAC ($.79). Expenditures on dental handpieces were estimated using the guidance...life span after which it is due for replacement. The effects of steam sterilization on dental handpieces decreases their life span substantially... handpieces should be sterilized between patients. ADA 18 May, 1992. 12. Reddy, T.G. Director, Dental Services, US Army Health Services Command

Blood volume and red cell life span (M113), part C

NASA Technical Reports Server (NTRS)

Johnson, P. C., Jr.

1973-01-01

Prechamber, in-chamber, and postchamber blood samples taken from Skylab simulation crewmembers did not indicate significant shortening of the red cell life span during the mission. This does not suggest that the space simulation environment could not be associated with red cell enzyme changes. It does show that any changes in enzymes were not sufficiently great to significantly shorten red cell survival. There was no evidence of bone marrow erythropoetic suppression nor was there any evidence of increased red cell destruction.

Rapamycin: the cure for all that ails.

PubMed

Hasty, Paul

2010-02-01

Target of rapamycin (TOR) signaling stimulates cell growth by regulating protein synthesis in response to a variety of stimuli in a wide range of species and is inhibited by rapamycin, a naturally occurring antifungal compound produced by bacteria and discovered on Easter Island or in the local vernacular, Rapa Nui (rapamycin's namesake). Recently, rapamycin was shown to extend life span for mice, even when administered late in life, suggesting that inhibiting the mammalian TOR pathway may improve health span for people.

Relating Life-Span Research to the Development of Gifted and Talented Children. Abstracts of Selected Papers [from] The Annual Esther Katz Rosen Symposium on the Psychological Development of Gifted Children (3rd, Lawrence, Kansas, February 19-20, 1993).

ERIC Educational Resources Information Center

Kansas Univ., Lawrence.

This monograph presents abstracts of 29 papers that relate life-span research to the development of gifted and talented children. Sample topics include: attitudes about rural schools and programs for the gifted; social competence, self-esteem, and parent-child time and interaction in an advantaged subculture; helping families of gifted children…

Personality, self-rated health, and subjective age in a life-span sample: the moderating role of chronological age.

PubMed

Stephan, Yannick; Demulier, Virginie; Terracciano, Antonio

2012-12-01

The present study tested whether chronological age moderates the association between subjective age and self-rated health and personality in a community-dwelling life-span sample (N = 1,016; age range: 18-91 years). Self-rated health, extraversion, and openness to experience were associated with a younger subjective age at older ages. Conscientious individuals felt more mature early in life. Conscientiousness, neuroticism, and agreeableness were not related to subjective age at older ages. These findings suggest that with aging self-rated health and personality traits are increasingly important for subjective age. 2013 APA, all rights reserved

Effect of petroleum-derived substances on life history traits of black bean aphid (Aphis fabae Scop.) and on the growth and chemical composition of broad bean.

PubMed

Rusin, Milena; Gospodarek, Janina; Nadgórska-Socha, Aleksandra; Barczyk, Gabriela

2017-04-01

The aim of the study was to determine the effects of various petroleum-derived substances, namely petrol, diesel fuel and spent engine oil, on life history traits and population dynamics of the black bean aphid Aphis fabae Scop. and on growth and chemical composition of its host plant Vicia faba L. Each substance was tested separately, using two concentrations (9 g kg -1 and 18 g kg -1 ). The experiment was conducted in four replications (four pots with five plants in each pot per treatment). Plants were cultivated in both control and contaminated soils. After six weeks from soil contamination and five weeks from sowing the seeds, observations of the effect of petroleum-derived substances on traits of three successive generations of aphids were conducted. Aphids were inoculated separately on leaves using cylindrical cages hermetically closed on both sides. Contamination of aphid occurred through its host plant. Results showed that all tested substances adversely affected A. fabae life history traits and population dynamics: extension of the prereproductive period, reduction of fecundity and life span, reduction of the population intrinsic growth rate. In broad bean, leaf, roots, and shoot growth was also impaired in most conditions, whereas nutrient and heavy metal content varied according to substances, their concentration, as well as plant part analysed. Results indicate that soil contamination with petroleum-derived substances entails far-reaching changes not only in organisms directly exposed to these pollutants (plants), but also indirectly in herbivores (aphids) and consequently provides information about potential negative effects on further links of the food chain, i.e., for predators and parasitoids.

Recent developments in the effort to cure HIV infection: going beyond N = 1.

PubMed

Siliciano, Janet D; Siliciano, Robert F

2016-02-01

Combination antiretroviral therapy (ART) can suppress plasma HIV to undetectable levels, allowing HIV-infected individuals who are treated early a nearly normal life span. Despite the clear ability of ART to prevent morbidity and mortality, it is not curative. Even in individuals who have full suppression of viral replication on ART, there are resting memory CD4+ T cells that harbor stably integrated HIV genomes, which are capable of producing infectious virus upon T cell activation. This latent viral reservoir is considered the primary obstacle to the development of an HIV cure, and recent efforts in multiple areas of HIV research have been brought to bear on the development of strategies to eradicate or develop a functional cure for HIV. Reviews in this series detail progress in our understanding of the molecular and cellular mechanisms of viral latency, efforts to accurately assess the size and composition of the latent reservoir, the characterization and development of HIV-targeted broadly neutralizing antibodies and cytolytic T lymphocytes, and animal models for the study HIV latency and therapeutic strategies.

Autism and exergaming: effects on repetitive behaviors and cognition.

PubMed

Anderson-Hanley, Cay; Tureck, Kimberly; Schneiderman, Robyn L

2011-01-01

Autism is a neurodevelopmental disorder that leads to impairment in social skills and delay in language development, and results in repetitive behaviors and restricted interests that impede academic and social involvement. Physical exercise has been shown to decrease repetitive behaviors in autistic children and improve cognitive function across the life-span. Exergaming combines physical and mental exercise simultaneously by linking physical activity movements to video game control and may yield better compliance with exercise. In this investigation, two pilot studies explored the potential behavioral and cognitive benefits of exergaming. In Pilot I, twelve children with autism spectrum disorders completed a control task and an acute bout of Dance Dance Revolution (DDR); in Pilot II, ten additional youths completed an acute bout of cyber cycling. Repetitive behaviors and executive function were measured before and after each activity. Repetitive behaviors significantly decreased, while performance on Digits Backwards improved following the exergaming conditions compared with the control condition. Additional research is needed to replicate these findings, and to explore the application of exergaming for the management of behavioral disturbance and to increase cognitive control in children on the autism spectrum.

[Telomerase activity in uveal melanomas].

PubMed

Rohrbach, J M; Riedinger, C; Wild, M; Partsch, M

2000-05-01

The maximum number of cell divisions of a certain cell population is genetically fixed so that aging cells become non-dividing (senescent) at least. This replicative life span, also known as "Hayflick limit", is probably defined by a "critical" length of the telomeres. Telomeres are special DNA-sequences located at the four ends of the chromosomes which are shortened with each cell cycle. Cells of most, but not all malignant tumours have been shown to reactivate the enzyme telomerase so that telomeres can be reconstructed, "Hayflick limit" can be overcome, and unlimited cell division can be established. This study was undertaken to elucidate whether telomerase reactivation is used by uveal melanoma cells. Fresh tumour tissue was removed from 10 untreated uveal melanomas after enucleation. Telomerase activity was determined using a PCR ELISA according to the Telomeric Repeat Amplification Protocol (TRAP). Normal tissue of the skin and the conjunctiva served as control. Telomerase activity was detectable in 90% of the investigated uveal melanomas. All control specimens were telomerase negative. Uveal melanoma growth seems to depend on telomerase reactivation. Thus, telomerase inhibition could offer a new principle for uveal melanoma therapy in the future.

Autism and exergaming: effects on repetitive behaviors and cognition

PubMed Central

Anderson-Hanley, Cay; Tureck, Kimberly; Schneiderman, Robyn L

2011-01-01

Autism is a neurodevelopmental disorder that leads to impairment in social skills and delay in language development, and results in repetitive behaviors and restricted interests that impede academic and social involvement. Physical exercise has been shown to decrease repetitive behaviors in autistic children and improve cognitive function across the life-span. Exergaming combines physical and mental exercise simultaneously by linking physical activity movements to video game control and may yield better compliance with exercise. In this investigation, two pilot studies explored the potential behavioral and cognitive benefits of exergaming. In Pilot I, twelve children with autism spectrum disorders completed a control task and an acute bout of Dance Dance Revolution (DDR); in Pilot II, ten additional youths completed an acute bout of cyber cycling. Repetitive behaviors and executive function were measured before and after each activity. Repetitive behaviors significantly decreased, while performance on Digits Backwards improved following the exergaming conditions compared with the control condition. Additional research is needed to replicate these findings, and to explore the application of exergaming for the management of behavioral disturbance and to increase cognitive control in children on the autism spectrum. PMID:22114543

Orexin (hypocretin) gene transfer diminishes narcoleptic sleep behavior in mice

PubMed Central

Liu, Meng; Thankachan, Stephen; Kaur, Satvinder; Begum, Suraiya; Blanco-Centurion, Carlos; Sakurai, Takeshi; Yanagisawa, Masashi; Neve, Rachael; Shiromani, Priyattam J.

2008-01-01

Gene transfer has proven to be an effective neurobiological tool in a number of neurodegenerative diseases, but it is not known if it can correct a sleep disorder. Narcolepsy is a neurodegenerative sleep disorder linked to the loss of neurons containing the neuropeptide orexin, also known as hypocretin. Here, a replication-defective herpes simplex virus-1 amplicon-based vector was constructed to transfer the gene for mouse prepro-orexin into mice with a genetic deletion of the orexin gene. After in vitro tests confirmed successful gene transfer into cells, the gene vector was delivered to the lateral hypothalamus of orexin knockout (KO) mice where the orexin peptide was robustly expressed in the somata and processes of numerous neurons, and the peptide product was detected in the cerebrospinal fluid. During the 4-day life-span of the vector the incidence of cataplexy declined by 60%, and the levels of rapid eye movement sleep during the second half of the night were similar to levels in wild-type mice, indicating that narcoleptic sleep–wake behavior in orexin KO mice can be improved by targeted gene transfer. PMID:18973565

The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity.

PubMed

Cantó, Carles; Houtkooper, Riekelt H; Pirinen, Eija; Youn, Dou Y; Oosterveer, Maaike H; Cen, Yana; Fernandez-Marcos, Pablo J; Yamamoto, Hiroyasu; Andreux, Pénélope A; Cettour-Rose, Philippe; Gademann, Karl; Rinsch, Chris; Schoonjans, Kristina; Sauve, Anthony A; Auwerx, Johan

2012-06-06

As NAD(+) is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38-both NAD(+) consumers-increases NAD(+) bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD(+) precursor with the ability to increase NAD(+) levels, Sir2-dependent gene silencing, and replicative life span in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD(+) levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high-fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin NR could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function. Copyright © 2012 Elsevier Inc. All rights reserved.

Erythrocyte and blood antibacterial defense.

PubMed

Minasyan, Hayk

2014-06-01

It is an axiom that blood cellular immunity is provided by leukocytes. As to erythrocytes, it is generally accepted that their main function is respiration. Our research provides objective video and photo evidence regarding erythrocyte bactericidal function. Phase-contrast immersion vital microscopy of the blood of patients with bacteremia was performed, and the process of bacteria entrapping and killing by erythrocytes was shot by means of video camera. Video evidence demonstrates that human erythrocytes take active part in blood bactericidal action and can repeatedly engulf and kill bacteria of different species and size. Erythrocytes are extremely important integral part of human blood cellular immunity. a) are more numerous; b) are able to entrap and kill microorganisms repeatedly without being injured; c) are more resistant to infection and better withstand the attacks of pathogens; d) have longer life span and are produced faster; e) are inauspicious media for proliferation of microbes and do not support replication of chlamidiae, mycoplasmas, rickettsiae, viruses, etc.; and f) are more effective and uncompromised bacterial killers. Blood cellular immunity theory and traditional view regarding the function of erythrocytes in human blood should be revised.

The life story of hydrogen peroxide II: a periodic pH and thermochemical drive for the RNA world

PubMed Central

Ball, Rowena; Brindley, John

2015-01-01

It is now accepted that primordial non-cellular RNA communities must have been subject to a periodic drive in order to replicate and prosper. We have proposed the oxidation of thiosulfate by hydrogen peroxide as this drive. This reaction system behaves as (i) a thermochemical and (ii) a pH oscillator, and in this work, we unify (i) and (ii) for the first time. We report thermally self-consistent, dynamical simulations in which the system transitions smoothly from nearly isothermal pH to fully developed thermo-pH oscillatory regimes. We use this oscillator to drive simulated replication of a 39-bp RNA species. Production of replicated duplex under thermo-pH drive was significantly enhanced compared with that under purely thermochemical drive, effectively allowing longer strands to replicate. Longer strands are fitter, with more potential to evolve enzyme activity and resist degradation. We affirm that concern over the alleged toxicity of hydrogen peroxide to life is largely misplaced in the current context, we survey its occurrence in the solar system to motivate its inclusion as a biosignature in the search for life on other worlds and highlight that pH oscillations in a spatially extended, bounded system manifest as the fundamental driving force of life: a proton gradient. PMID:26202683

Mars, clays and the origins of life

NASA Technical Reports Server (NTRS)

Hartman, Hyman

1989-01-01

To detect life in the Martian soil, tests were designed to look for respiration and photosynthesis. Both tests (labeled release, LR, and pyrolytic release, PR) for life in the Martian soils were positive. However, when the measurement for organic molecules in the soil of Mars was made, none were found. The interpretation given is that the inorganic constituents of the soil of Mars were responsible for these observations. The inorganic analysis of the soil was best fitted by a mixture of minerals: 60 to 80 percent clay, iron oxide, quartz, and soluble salts such as halite (NaCl). The minerals most successful in simulating the PR and LR experiments are iron-rich clays. There is a theory that considers clays as the first organisms capable of replication, mutation, and catalysis, and hence of evolving. Clays are formed when liquid water causes the weathering of rocks. The distribution of ions such as aluminum, magnesium, and iron play the role of bases in the DNA. The information was stored in the distribution of ions in the octahedral and tetrahedral molecules, but that they could, like RNA and DNA, replicate. When the clays replicated, each sheet of clay would be a template for a new sheet. The ion substitutions in one clay sheet would give rise to a complementary or similar pattern on the clay synthesized on its surface. It was theorized that it was on the surface of replicating iron-rich clays that carbon dioxide would be fixed in the light into organic acids such as formic or oxalic acid. If Mars had liquid water during a warm period in its past, clay formation would have been abundant. These clays would have replicated and evolved until the liquid water was removed due to cooling of Mars. It is entirely possible that the Viking mission detected life on Mars, but it was clay life that awaits the return of water to continue its evolution into life based on organic molecules.

Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley

Here, evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). Design, Setting, and Participants A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n=644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro inmore » the laboratory for DNA damage response. The study included African and Asian elephants (n=8), patients with LFS (n=10), and age-matched human controls (n=11). Human samples were collected at the University of Utah between June 2014 and July 2015. Exposures Ionizing radiation and doxorubicin. Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95% CI, 0%-5%]; African wild dog, 8% [95% CI, 0%-16%]; lion, 2% [95% CI, 0%-7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95% CI, 3.14%-6.49%), compared with humans, who have 11% to 25% cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95% CI, 1.93%-3.48%] vs human controls, 7.17% [95% CI, 5.91%-8.44%] vs elephants, 14.64% [95% CI, 10.91%-18.37%]; P<.001; doxorubicin exposure: human controls, 8.10% [95% CI, 6.55%-9.66%] vs elephants, 24.77% [95% CI, 23.0%-26.53%]; P<.001). Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.« less

Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans

DOE PAGES

Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley; ...

2015-10-08

Here, evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). Design, Setting, and Participants A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n=644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro inmore » the laboratory for DNA damage response. The study included African and Asian elephants (n=8), patients with LFS (n=10), and age-matched human controls (n=11). Human samples were collected at the University of Utah between June 2014 and July 2015. Exposures Ionizing radiation and doxorubicin. Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95% CI, 0%-5%]; African wild dog, 8% [95% CI, 0%-16%]; lion, 2% [95% CI, 0%-7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95% CI, 3.14%-6.49%), compared with humans, who have 11% to 25% cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95% CI, 1.93%-3.48%] vs human controls, 7.17% [95% CI, 5.91%-8.44%] vs elephants, 14.64% [95% CI, 10.91%-18.37%]; P<.001; doxorubicin exposure: human controls, 8.10% [95% CI, 6.55%-9.66%] vs elephants, 24.77% [95% CI, 23.0%-26.53%]; P<.001). Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.« less

Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans.

PubMed

Abegglen, Lisa M; Caulin, Aleah F; Chan, Ashley; Lee, Kristy; Robinson, Rosann; Campbell, Michael S; Kiso, Wendy K; Schmitt, Dennis L; Waddell, Peter J; Bhaskara, Srividya; Jensen, Shane T; Maley, Carlo C; Schiffman, Joshua D

2015-11-03

Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. Ionizing radiation and doxorubicin. Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95% CI, 0%-5%]; African wild dog, 8% [95% CI, 0%-16%]; lion, 2% [95% CI, 0%-7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95% CI, 3.14%-6.49%), compared with humans, who have 11% to 25% cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95% CI, 1.93%-3.48%] vs human controls, 7.17% [95% CI, 5.91%-8.44%] vs elephants, 14.64% [95% CI, 10.91%-18.37%]; P < .001; doxorubicin exposure: human controls, 8.10% [95% CI, 6.55%-9.66%] vs elephants, 24.77% [95% CI, 23.0%-26.53%]; P < .001). Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.

Phosphorylation of the Bacillus subtilis Replication Controller YabA Plays a Role in Regulation of Sporulation and Biofilm Formation

PubMed Central

García García, Tránsito; Ventroux, Magali; Derouiche, Abderahmane; Bidnenko, Vladimir; Correia Santos, Sara; Henry, Céline; Mijakovic, Ivan; Noirot-Gros, Marie-Françoise; Poncet, Sandrine

2018-01-01

Bacillus subtilis cells can adopt different life-styles in response to various environmental cues, including planktonic cells during vegetative growth, sessile cells during biofilm formation and sporulation. While switching life-styles, bacteria must coordinate the progression of their cell cycle with their physiological status. Our current understanding of the regulatory pathways controlling the decision-making processes and triggering developmental switches highlights a key role of protein phosphorylation. The regulatory mechanisms that integrate the bacterial chromosome replication status with sporulation involve checkpoint proteins that target the replication initiator DnaA or the kinase phosphorelay controlling the master regulator Spo0A. B. subtilis YabA is known to interact with DnaA to prevent over-initiation of replication during vegetative growth. Here, we report that YabA is phosphorylated by YabT, a Ser/Thr kinase expressed during sporulation and biofilm formation. The phosphorylation of YabA has no effect on replication initiation control but hyper-phosphorylation of YabA leads to an increase in sporulation efficiency and a strong inhibition of biofilm formation. We also provide evidence that YabA phosphorylation affects the level of Spo0A-P in cells. These results indicate that YabA is a multifunctional protein with a dual role in regulating replication initiation and life-style switching, thereby providing a potential mechanism for cross-talk and coordination of cellular processes during adaptation to environmental change. PMID:29619013

Phosphorylation of the Bacillus subtilis Replication Controller YabA Plays a Role in Regulation of Sporulation and Biofilm Formation.

PubMed

García García, Tránsito; Ventroux, Magali; Derouiche, Abderahmane; Bidnenko, Vladimir; Correia Santos, Sara; Henry, Céline; Mijakovic, Ivan; Noirot-Gros, Marie-Françoise; Poncet, Sandrine

2018-01-01

Bacillus subtilis cells can adopt different life-styles in response to various environmental cues, including planktonic cells during vegetative growth, sessile cells during biofilm formation and sporulation. While switching life-styles, bacteria must coordinate the progression of their cell cycle with their physiological status. Our current understanding of the regulatory pathways controlling the decision-making processes and triggering developmental switches highlights a key role of protein phosphorylation. The regulatory mechanisms that integrate the bacterial chromosome replication status with sporulation involve checkpoint proteins that target the replication initiator DnaA or the kinase phosphorelay controlling the master regulator Spo0A. B. subtilis YabA is known to interact with DnaA to prevent over-initiation of replication during vegetative growth. Here, we report that YabA is phosphorylated by YabT, a Ser/Thr kinase expressed during sporulation and biofilm formation. The phosphorylation of YabA has no effect on replication initiation control but hyper-phosphorylation of YabA leads to an increase in sporulation efficiency and a strong inhibition of biofilm formation. We also provide evidence that YabA phosphorylation affects the level of Spo0A-P in cells. These results indicate that YabA is a multifunctional protein with a dual role in regulating replication initiation and life-style switching, thereby providing a potential mechanism for cross-talk and coordination of cellular processes during adaptation to environmental change.

National prevalence of posttraumatic stress disorder among sexually revictimized adolescent, college, and adult household-residing women.

PubMed

Walsh, Kate; Danielson, Carla Kmett; McCauley, Jenna L; Saunders, Benjamin E; Kilpatrick, Dean G; Resnick, Heidi S

2012-09-01

Despite empirical links between sexual revictimization (ie, experiencing 2 or more sexual assaults) and posttraumatic stress disorder (PTSD), to our knowledge, no epidemiological studies document the prevalence of sexual revictimization and PTSD. Establishing estimates is essential to determine the scope, public health impact, and psychiatric sequelae of sexual revictimization. To estimate the prevalence of sexual revictimization and PTSD among 3 national female samples (adolescent, college, and adult household probability). Surveys were used to collect data from the National Women's Study-Replication (2006; college) as well as household probability samples from the National Survey of Adolescents-Replication (2005) and the National Women's Study-Replication (2006; household probability). Households and college campuses across the United States. One thousand seven hundred sixty-three adolescent girls, 2000 college women, and 3001 household-residing adult women. Behaviorally specific questions assessed unwanted sexual acts occurring over the life span owing to the use of force, threat of force, or incapacitation via drug or alcohol use. Posttraumatic stress disorder was assessed with a module validated against the criterion standard Structured Clinical Interview for DSM-IV. About 53% of victimized adolescents, 50% of victimized college women, and 58.8% of victimized household-residing women reported sexual revictimization. Current PTSD was reported by 20% of revictimized adolescents, 40% of revictimized college women, and 27.2% of revictimized household-residing women. Compared with nonvictims, odds of meeting past 6-month PTSD were 4.3 to 8.2 times higher for revictimized respondents and 2.4 to 3.5 times higher for single victims. Population prevalence estimates suggest that 769 000 adolescent girls, 625 000 college women, and 13.4 million women in US households reported sexual revictimization. Further, 154 000 sexually revictimized adolescents, 250 000 sexually revictimized college women, and 3.6 million sexually revictimized household women met criteria for past 6-month PTSD. Findings highlight the importance of screening for sexual revictimization and PTSD in pediatric, college, and primary care settings.

The Tölz Temporal Topography Study: mapping the visual field across the life span. Part II: cognitive factors shaping visual field maps.

PubMed

Poggel, Dorothe A; Treutwein, Bernhard; Calmanti, Claudia; Strasburger, Hans

2012-08-01

Part I described the topography of visual performance over the life span. Performance decline was explained only partly by deterioration of the optical apparatus. Part II therefore examines the influence of higher visual and cognitive functions. Visual field maps for 95 healthy observers of static perimetry, double-pulse resolution (DPR), reaction times, and contrast thresholds, were correlated with measures of visual attention (alertness, divided attention, spatial cueing), visual search, and the size of the attention focus. Correlations with the attentional variables were substantial, particularly for variables of temporal processing. DPR thresholds depended on the size of the attention focus. The extraction of cognitive variables from the correlations between topographical variables and participant age substantially reduced those correlations. There is a systematic top-down influence on the aging of visual functions, particularly of temporal variables, that largely explains performance decline and the change of the topography over the life span.

Effects of High Magneto-Gravitational Environment on Silkworm Embryogenesis

NASA Astrophysics Data System (ADS)

Tian, Zongcheng; Li, Muwang; Qian, Airong; Xu, Huiyun; Wang, Zhe; Di, Shengmeng; Yang, Pengfei; Hu, Lifang; Ding, Chong; Zhang, Wei; Luo, Mingzhi; Han, Jing; Gao, Xiang; Huang, Yongping; Shang, Peng

2010-04-01

The objective of this research was to observe whether silkworm embryos can survive in a high magneto-gravitational environment (HMGE) and what significant phenotype changes can be produced. The hatching rate, hatching time, life span, growth velocity and cocoon weight of silkworm were measured after silkworm embryos were exposed to HMGE (0 g, 12 T; 1 g, 16 T; and 2 g, 12 T) for a period of time. Compared with the control group, 0 g exposure resulted in a lower hatching rate and a shorter life span. Statistically insignificant morphological changes had been observed for larvae growth velocity, incidence of abnormal markings and weight of cocoons. These results suggest that the effect of HMGE on silkworm embryogenesis is not lethal. Bio-effects of silkworm embryogenesis at 0 g in a HMGE were similar with those of space flight. The hatching time, life span and hatching rates of silkworm may be potential phenotype markers related to exposure in a weightless environment.

Review of certain low-level ionizing radiation studies in mice and guinea pigs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Congdon, C.C.

1987-05-01

Starting in the early 1940s, Egon Lorenz and collaborators at the National Cancer Institute began an extended study of chronic low-level ionizing radiation effects in what was then the tolerance range for man. Observations on life span, body weight and radiation carcinogenesis, among others, were made in mice, guinea pigs and rabbits. At the then-permissible exposure level, 0.1 R** per 8-h day until natural death, experimental mice and guinea pigs had a slightly greater mean life span compared to control animals. In addition, there was marked weight gain during the growth phase in both species. Increased tumor incidence was alsomore » observed at the 0.1-R level in mice. The primary hypothesis for increased median life span has been rebound regenerative hyperplasia during the early part of the exposure; in the presence of continuing injury, there is physiological enhancement of defense mechanisms against intercurrent infection. The body weight gain has not been explained. 32 references.« less

Spermidine: a novel autophagy inducer and longevity elixir.

PubMed

Madeo, Frank; Eisenberg, Tobias; Büttner, Sabrina; Ruckenstuhl, Christoph; Kroemer, Guido

2010-01-01

Spermidine is a ubiquitous polycation that is synthesized from putrescine and serves as a precursor of spermine. Putrescine, spermidine and spermine all are polyamines that participate in multiple known and unknown biological processes. Exogenous supply of spermidine prolongs the life span of several model organisms including yeast (Saccharomyces cerevisiae), nematodes (Caenorhabditis elegans) and flies (Drosophila melanogaster) and significantly reduces age-related oxidative protein damage in mice, indicating that this agent may act as a universal anti-aging drug. Spermidine induces autophagy in cultured yeast and mammalian cells, as well as in nematodes and flies. Genetic inactivation of genes essential for autophagy abolishes the life span-prolonging effect of spermidine in yeast, nematodes and flies. These findings complement expanding evidence that autophagy mediates cytoprotection against a variety of noxious agents and can confer longevity when induced at the whole-organism level. We hypothesize that increased autophagic turnover of cytoplasmic organelles or long-lived proteins is involved in most if not all life span-prolonging therapies.

Conditional inhibition of autophagy genes in adult Drosophila impairs immunity without compromising longevity.

PubMed

Ren, Chunli; Finkel, Steven E; Tower, John

2009-03-01

Immune function declines with age in Drosophila and humans, and autophagy is implicated in immune function. In addition, autophagy genes are required for life span extension caused by reduced insulin/IGF1-like signaling and dietary restriction in Caenorhabditiselegans. To test if the autophagy pathway might be limiting for immunity and/or life span in adult Drosophila, the Geneswitch system was used to cause conditional inactivation of the autophagy genes Atg5, Atg7 and Atg12 by RNAi. Conditional inhibition of Atg genes in adult flies reduced lysotracker staining of adult tissues, and reduced resistance to injected Escherichia coli, as evidenced by increased bacterial titers and reduced fly survival. However, survival of uninjected flies was unaffected by Atg gene inactivation. The data indicate that Atg gene activity is required for normal immune function in adult flies, and suggest that neither autophagy nor immune function are limiting for adult life span under typical laboratory conditions.

Variation in Age and Size in Fennoscandian Three-Spined Sticklebacks (Gasterosteus aculeatus)

PubMed Central

DeFaveri, Jacquelin; Merilä, Juha

2013-01-01

Average age and maximum life span of breeding adult three-spined sticklebacks (Gasterosteus aculeatus) were determined in eight Fennoscandian localities with the aid of skeletochronology. The average age varied from 1.8 to 3.6 years, and maximum life span from three to six years depending on the locality. On average, fish from marine populations were significantly older than those from freshwater populations, but variation within habitat types was large. We also found significant differences in mean body size among different habitat types and populations, but only the population differences remained significant after accounting for variation due to age effects. These results show that generation length and longevity in three-spined sticklebacks can vary significantly from one locality to another, and that population differences in mean body size cannot be explained as a simple consequence of differences in population age structure. We also describe a nanistic population from northern Finland exhibiting long life span and small body size. PMID:24260496

Variation in age and size in Fennoscandian three-spined sticklebacks (Gasterosteus aculeatus).

PubMed

DeFaveri, Jacquelin; Merilä, Juha

2013-01-01

Average age and maximum life span of breeding adult three-spined sticklebacks (Gasterosteus aculeatus) were determined in eight Fennoscandian localities with the aid of skeletochronology. The average age varied from 1.8 to 3.6 years, and maximum life span from three to six years depending on the locality. On average, fish from marine populations were significantly older than those from freshwater populations, but variation within habitat types was large. We also found significant differences in mean body size among different habitat types and populations, but only the population differences remained significant after accounting for variation due to age effects. These results show that generation length and longevity in three-spined sticklebacks can vary significantly from one locality to another, and that population differences in mean body size cannot be explained as a simple consequence of differences in population age structure. We also describe a nanistic population from northern Finland exhibiting long life span and small body size.

All about Animal Life Cycles. Animal Life for Children. [Videotape].

ERIC Educational Resources Information Center

2000

While watching the development from tadpole to frog, caterpillar to butterfly, and pup to wolf, children learn about the life cycles of animals, the different stages of development, and the average life spans of a variety of creatures. This videotape correlates to the following National Science Education Standards for Life Science: characteristics…

Bütschli dynamic droplet system.

PubMed

Armstrong, Rachel; Hanczyc, Martin

2013-01-01

Dynamical oil-water systems such as droplets display lifelike properties and may lend themselves to chemical programming to perform useful work, specifically with respect to the built environment. We present Bütschli water-in-oil droplets as a model for further investigation into the development of a technology with living properties. Otto Bütschli first described the system in 1898, when he used alkaline water droplets in olive oil to initiate a saponification reaction. This simple recipe produced structures that moved and exhibited characteristics that resembled, at least superficially, the amoeba. We reconstructed the Bütschli system and observed its life span under a light microscope, observing chemical patterns and droplet behaviors in nearly three hundred replicate experiments. Self-organizing patterns were observed, and during this dynamic, embodied phase the droplets provided a means of introducing temporal and spatial order in the system with the potential for chemical programmability. The authors propose that the discrete formation of dynamic droplets, characterized by their lifelike behavior patterns, during a variable window of time (from 30 s to 30 min after the addition of alkaline water to the oil phase), qualify this system as an example of living technology. The analysis of the Bütschli droplets suggests that a set of conditions may precede the emergence of lifelike characteristics and exemplifies the richness of this rudimentary chemical system, not only for artificial life investigations but also for possible real-world applications in architectural practice.

Replication of poliovirus RNA and subgenomic RNA transcripts in transfected cells.

PubMed Central

Collis, P S; O'Donnell, B J; Barton, D J; Rogers, J A; Flanegan, J B

1992-01-01

Full-length and subgenomic poliovirus RNAs were transcribed in vitro and transfected into HeLa cells to study viral RNA replication in vivo. RNAs with deletion mutations were analyzed for the ability to replicate in either the absence or the presence of helper RNA by using a cotransfection procedure and Northern (RNA) blot analysis. An advantage of this approach was that viral RNA replication and genetic complementation could be characterized without first isolating conditional-lethal mutants. A subgenomic RNA with a large in-frame deletion in the capsid coding region (P1) replicated more efficiently than full-length viral RNA transcripts. In cotransfection experiments, both the full-length and subgenomic RNAs replicated at slightly reduced levels and appeared to interfere with each other's replication. In contrast, a subgenomic RNA with a similarly sized out-of-frame deletion in P1 did not replicate in transfected cells, either alone or in the presence of helper RNA. Similar results were observed with an RNA transcript containing a large in-frame deletion spanning the P1, P2, and P3 coding regions. A mutant RNA with an in-frame deletion in the P1-2A coding sequence was self-replicating but at a significantly reduced level. The replication of this RNA was fully complemented after cotransfection with a helper RNA that provided 2A in trans. A P1-2A-2B in-frame deletion, however, totally blocked RNA replication and was not complemented. Control experiments showed that all of the expected viral proteins were both synthesized and processed when the RNA transcripts were translated in vitro. Thus, our results indicated that 2A was a trans-acting protein and that 2B and perhaps other viral proteins were cis acting during poliovirus RNA replication in vivo. Our data support a model for poliovirus RNA replication which directly links the translation of a molecule of plus-strand RNA with the formation of a replication complex for minus-strand RNA synthesis. Images PMID:1328676

Holistic life-span health outcomes among elite intercollegiate student-athletes.

PubMed

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 < .001; d = 1.05; pCID = 85%; OR = 5.8, 95% CI = 2.0, 16) and current students (P < .001; d = 2.25; pCID >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 cardiopulmonary health, and differences in life-span psychosocial health and HRQL profiles compared with NAs. These data provide timely evidence regarding a compelling public issue and highlight the need for further study of life-span health among modern athletes.

Holistic Life-Span Health Outcomes Among Elite Intercollegiate Student–Athletes

PubMed Central

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

Context: 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. Objective: To assess holistic life-span health and health-related quality-of-life (HRQL) among current and former National Collegiate Athletic Association student–athletes (SAs). Design: Cross-sectional study. Setting: A large Division I university. Patients or Other Participants: 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. Main Outcome Measure(s): 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. Results: 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 < .001; d = 1.05; pCID = 85%; OR = 5.8, 95% CI = 2.0, 16) and current students (P < .001; d = 2.25; pCID >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. Conclusions: The SAs demonstrated significant, clinically meaningful evidence of greater joint health concerns later in life, comparable cardiopulmonary health, and differences in life-span psychosocial health and HRQL profiles compared with NAs. These data provide timely evidence regarding a compelling public issue and highlight the need for further study of life-span health among modern athletes. PMID:25117874

Ecology and Evolution in the RNA World Dynamics and Stability of Prebiotic Replicator Systems.

PubMed

Szilágyi, András; Zachar, István; Scheuring, István; Kun, Ádám; Könnyű, Balázs; Czárán, Tamás

2017-11-27

As of today, the most credible scientific paradigm pertaining to the origin of life on Earth is undoubtedly the RNA World scenario. It is built on the assumption that catalytically active replicators (most probably RNA-like macromolecules) may have been responsible for booting up life almost four billion years ago. The many different incarnations of nucleotide sequence (string) replicator models proposed recently are all attempts to explain on this basis how the genetic information transfer and the functional diversity of prebiotic replicator systems may have emerged, persisted and evolved into the first living cell. We have postulated three necessary conditions for an RNA World model system to be a dynamically feasible representation of prebiotic chemical evolution: (1) it must maintain and transfer a sufficient diversity of information reliably and indefinitely, (2) it must be ecologically stable and (3) it must be evolutionarily stable. In this review, we discuss the best-known prebiotic scenarios and the corresponding models of string-replicator dynamics and assess them against these criteria. We suggest that the most popular of prebiotic replicator systems, the hypercycle, is probably the worst performer in almost all of these respects, whereas a few other model concepts (parabolic replicator, open chaotic flows, stochastic corrector, metabolically coupled replicator system) are promising candidates for development into coherent models that may become experimentally accessible in the future.

Ecology and Evolution in the RNA World Dynamics and Stability of Prebiotic Replicator Systems

PubMed Central

Szilágyi, András; Kun, Ádám; Könnyű, Balázs; Czárán, Tamás

2017-01-01

As of today, the most credible scientific paradigm pertaining to the origin of life on Earth is undoubtedly the RNA World scenario. It is built on the assumption that catalytically active replicators (most probably RNA-like macromolecules) may have been responsible for booting up life almost four billion years ago. The many different incarnations of nucleotide sequence (string) replicator models proposed recently are all attempts to explain on this basis how the genetic information transfer and the functional diversity of prebiotic replicator systems may have emerged, persisted and evolved into the first living cell. We have postulated three necessary conditions for an RNA World model system to be a dynamically feasible representation of prebiotic chemical evolution: (1) it must maintain and transfer a sufficient diversity of information reliably and indefinitely, (2) it must be ecologically stable and (3) it must be evolutionarily stable. In this review, we discuss the best-known prebiotic scenarios and the corresponding models of string-replicator dynamics and assess them against these criteria. We suggest that the most popular of prebiotic replicator systems, the hypercycle, is probably the worst performer in almost all of these respects, whereas a few other model concepts (parabolic replicator, open chaotic flows, stochastic corrector, metabolically coupled replicator system) are promising candidates for development into coherent models that may become experimentally accessible in the future. PMID:29186916

"Pull and push back" concepts of longevity and life span extension.

PubMed

Muradian, Khachik

2013-12-01

The negative relation between metabolism and life span is a fundamental gerontological discovery well documented in a variety of ontogenetic and phylogenetic models. But how the long-lived species and populations sustain lower metabolic rate and, in more general terms, what is the efficient way to decline the metabolism? The suggested 'pull and push back' hypothesis assumes that decreased Po2 (hypoxia) and/or increased [Formula: see text] (hypercapnia) may create preconditions for the declined metabolic and aging rates. However, wider implementation of such ideas is compromised because of little advances in modification of the metabolic rate. Artificial atmosphere with controlled [Formula: see text] and [Formula: see text] could be a promising approach because of the minimal external invasions and involvement of the backward and forward loops ensuring physiological self-regulation of the metabolic perturbations. General considerations and existing data indicate that manipulations of [Formula: see text] may be more efficient in life span extension than [Formula: see text]. Thus, maximum life span of mammals positively correlates with the blood [Formula: see text] and HCO3 (-) but not with [Formula: see text]. Yet, proportional decease of the body [Formula: see text] and increase of [Formula: see text] seems the most optimal regime ensuring lower losses of the energy equivalents. Furthermore, especially rewarding results could be expected when such changes are modeled without major external invasions using the animals' inner capacity to consume O2 and generate CO2, as it is typical for the extreme longevity.

Down regulation of miR-124 in both Werner syndrome DNA helicase mutant mice and mutant Caenorhabditis elegans wrn-1 reveals the importance of this microRNA in accelerated aging

PubMed Central

Dallaire, Alexandra; Garand, Chantal; Paquet, Eric R.; Mitchell, Sarah J.; de Cabo, Rafael; Simard, Martin J.

2012-01-01

Small non-coding microRNAs are believed to be involved in the mechanism of aging but nothing is known on the impact of microRNAs in the progeroid disorder Werner syndrome (WS). WS is a premature aging disorder caused by mutations in a RecQ-like DNA helicase. Mice lacking the helicase domain of the WRN ortholog exhibit many phenotypic features of WS, including a pro-oxidant status and a shorter mean life span. Caenorhabditis elegans (C. elegans) with a nonfunctional wrn-1 DNA helicase also exhibit a shorter life span. Thus, both models are relevant to study the expression of microRNAs involved in WS. In this study, we show that miR-124 expression is lost in the liver of Wrn helicase mutant mice. Interestingly, the expression of this conserved miR-124 in whole wrn-1 mutant worms is also significantly reduced. The loss of mir-124 in C. elegans increases reactive oxygen species formation and accumulation of the aging marker lipofuscin, reduces whole body ATP levels and results in a reduction in life span. Finally, supplementation of vitamin C normalizes the median life span of wrn-1 and mir-124 mutant worms. These results suggest that biological pathways involving WRN and miR-124 are conserved in the aging process across different species. PMID:23075628

Elevated CO2 and O3 effects on fine-root survivorship in ponderosa pine mesocosms.

PubMed

Phillips, Donald L; Johnson, Mark G; Tingey, David T; Storm, Marjorie J

2009-07-01

Atmospheric carbon dioxide (CO(2)) and ozone (O(3)) concentrations are rising, which may have opposing effects on tree C balance and allocation to fine roots. More information is needed on interactive CO(2) and O(3) effects on roots, particularly fine-root life span, a critical demographic parameter and determinant of soil C and N pools and cycling rates. We conducted a study in which ponderosa pine (Pinus ponderosa) seedlings were exposed to two levels of CO(2) and O(3) in sun-lit controlled-environment mesocosms for 3 years. Minirhizotrons were used to monitor individual fine roots in three soil horizons every 28 days. Proportional hazards regression was used to analyze effects of CO(2), O(3), diameter, depth, and season of root initiation on fine-root survivorship. More fine roots were produced in the elevated CO(2) treatment than in ambient CO(2). Elevated CO(2), increasing root diameter, and increasing root depth all significantly increased fine-root survivorship and median life span. Life span was slightly, but not significantly, lower in elevated O(3), and increased O(3) did not reduce the effect of elevated CO(2). Median life spans varied from 140 to 448 days depending on the season of root initiation. These results indicate the potential for elevated CO(2) to increase the number of fine roots and their residence time in the soil, which is also affected by root diameter, root depth, and phenology.

Loss of the clock protein PER2 shortens the erythrocyte life span in mice.

PubMed

Sun, Qi; Zhao, Yue; Yang, Yunxia; Yang, Xiao; Li, Minghui; Xu, Xi; Wen, Dan; Wang, Junsong; Zhang, Jianfa

2017-07-28

Cell proliferation and release from the bone marrow have been demonstrated to be controlled by circadian rhythms in both humans and mice. However, it is unclear whether local circadian clocks in the bone marrow influence physiological functions and life span of erythrocytes. Here, we report that loss of the clock gene Per2 significantly decreased erythrocyte life span. Mice deficient in Per2 were more susceptible to acute stresses in the erythrocytes, becoming severely anemic upon phenylhydrazine, osmotic, and H 2 O 2 challenges. 1 H NMR-based metabolomics analysis revealed that the Per2 depletion causes significant changes in metabolic profiles of erythrocytes, including increased lactate and decreased ATP levels compared with wild-type mice. The lower ATP levels were associated with hyperfunction of Na + /K + -ATPase activity in Per2 -null erythrocytes, and inhibition of Na + /K + -ATPase activity by ouabain efficiently rescued ATP levels. Per2 -null mice displayed increased levels of Na + /K + -ATPase α1 (ATP1A1) in the erythrocyte membrane, and transfection of Per2 cDNA into the erythroleukemic cell line TF-1 inhibited Atp1a1 expression. Furthermore, we observed that PER2 regulates Atp1a1 transcription through interacting with trans-acting transcription factor 1 (SP1). Our findings reveal that Per2 function in the bone marrow is required for the regulation of life span in circulating erythrocytes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Successful immortalization of mesenchymal progenitor cells derived from human placenta and the differentiation abilities of immortalized cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Xiaohong; Soda, Yasushi; Takahashi, Kenji

2006-12-29

We reported previously that mesenchymal progenitor cells derived from chorionic villi of the human placenta could differentiate into osteoblasts, adipocytes, and chondrocytes under proper induction conditions and that these cells should be useful for allogeneic regenerative medicine, including cartilage tissue engineering. However, similar to human mesenchymal stem cells (hMSCs), though these placental cells can be isolated easily, they are difficult to study in detail because of their limited life span in vitro. To overcome this problem, we attempted to prolong the life span of human placenta-derived mesenchymal cells (hPDMCs) by modifying hTERT and Bmi-1, and investigated whether these modified hPDMCsmore » retained their differentiation capability and multipotency. Our results indicated that the combination of hTERT and Bmi-1 was highly efficient in prolonging the life span of hPDMCs with differentiation capability to osteogenic, adipogenic, and chondrogenic cells in vitro. Clonal cell lines with directional differentiation ability were established from the immortalized parental hPDMC/hTERT + Bmi-1. Interestingly, hPDMC/Bmi-1 showed extended proliferation after long-term growth arrest and telomerase was activated in the immortal hPDMC/Bmi-1 cells. However, the differentiation potential was lost in these cells. This study reports a method to extend the life span of hPDMCs with hTERT and Bmi-1 that should become a useful tool for the study of mesenchymal stem cells.« less

The challenges in moving from ageing to successful longevity.

PubMed

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

2014-01-01

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

Development of the Life Story in Early Adolescence

ERIC Educational Resources Information Center

Steiner, Kristina L.; Pillemer, David B.

2018-01-01

Life span developmental psychology proposes that the ability to create a coherent life narrative does not develop until early adolescence. Using a novel methodology, 10-, 12-, and 14-year-old participants were asked to tell their life stories aloud to a researcher. Later, participants separated their transcribed narratives into self-identified…

Perceptions of Life Changes: An Alternate Measure of Aging through Time.

ERIC Educational Resources Information Center

Suggs, Patricia K.; Kivett, Vira R.

Retrospective strategies measuring perceived life changes over time can further the advancement of life span developmental research. Researchers have neglected the individual's perception of his/her life changes over time. This study attempts to determine discriminators of change over time as operationalized by perceptions of change. Subjects…

Experimentally guided models reveal replication principles that shape the mutation distribution of RNA viruses

PubMed Central

Schulte, Michael B; Draghi, Jeremy A; Plotkin, Joshua B; Andino, Raul

2015-01-01

Life history theory posits that the sequence and timing of events in an organism's lifespan are fine-tuned by evolution to maximize the production of viable offspring. In a virus, a life history strategy is largely manifested in its replication mode. Here, we develop a stochastic mathematical model to infer the replication mode shaping the structure and mutation distribution of a poliovirus population in an intact single infected cell. We measure production of RNA and poliovirus particles through the infection cycle, and use these data to infer the parameters of our model. We find that on average the viral progeny produced from each cell are approximately five generations removed from the infecting virus. Multiple generations within a single cell infection provide opportunities for significant accumulation of mutations per viral genome and for intracellular selection. DOI: http://dx.doi.org/10.7554/eLife.03753.001 PMID:25635405

Development of mRNA-specific RT-PCR for the detection of koi herpesvirus (KHV) replication stage.

PubMed

Yuasa, Kei; Kurita, Jun; Kawana, Morihiko; Kiryu, Ikunari; Oseko, Norihisa; Sano, Motohiko

2012-08-13

An mRNA-specific reverse transcription (RT)-PCR primer set spanning the exon junction of a spliced putative terminase gene in the koi herpesvirus (KHV) was developed to detect the replicating stage of the virus. The proposed RT-PCR amplified a target gene from the RNA template, but not from a DNA template extracted from common carp brain (CCB) cells infected with KHV. In addition, the RT-PCR did not amplify the target gene of templates extracted from specific cell lines infected with either CyHV-1 or CyHV-2. RT-PCR detected mRNA from the scales of koi experimentally infected with KHV at 24 h post exposure (hpe). However, unlike conventional PCR, RT-PCR could not detect KHV DNA in fish at 0 hpe. The results indicate that the RT-PCR developed in this study is mRNA-specific and that the assay can detect the replicating stage of KHV from both fish and cultured cells infected with the virus.

From Children to Adults: Motor Performance across the Life-Span

PubMed Central

Leversen, Jonas S. R.; Haga, Monika; Sigmundsson, Hermundur

2012-01-01

The life-span approach to development provides a theoretical framework to examine the general principles of life-long development. This study aims to investigate motor performance across the life span. It also aims to investigate if the correlations between motor tasks increase with aging. A cross-sectional design was used to describe the effects of aging on motor performance across age groups representing individuals from childhood to young adult to old age. Five different motor tasks were used to study changes in motor performance within 338 participants (7–79 yrs). Results showed that motor performance increases from childhood (7–9) to young adulthood (19–25) and decreases from young adulthood (19–25) to old age (66–80). These results are mirroring results from cognitive research. Correlation increased with increasing age between two fine motor tasks and two gross motor tasks. We suggest that the findings might be explained, in part, by the structural changes that have been reported to occur in the developing and aging brain and that the theory of Neural Darwinism can be used as a framework to explain why these changes occur. PMID:22719958

Inbreeding Depression and Male Survivorship in Drosophila: Implications for Senescence Theory

PubMed Central

Swindell, William R.; Bouzat, Juan L.

2006-01-01

The extent to which inbreeding depression affects longevity and patterns of survivorship is an important issue from several research perspectives, including evolutionary biology, conservation biology, and the genetic analysis of quantitative traits. However, few previous inbreeding depression studies have considered longevity as a focal life-history trait. We maintained laboratory populations of Drosophila melanogaster at census population sizes of 2 and 10 male-female pairs for up to 66 generations and performed repeated assays of male survivorship throughout this time period. On average, significant levels of inbreeding depression were observed for median life span and age-specific mortality. For age-specific mortality, the severity of inbreeding depression increased over the life span. We found that a baseline inbreeding load of 0.307 lethal equivalents per gamete affected age-specific mortality, and that this value increased at a rate of 0.046 per day of the life span. With respect to some survivorship parameters, the differentiation of lineages was nonlinear with respect to the inbreeding coefficient, which suggested that nonadditive genetic variation contributed to variation among lineages. These findings provide insights into the genetic basis of longevity as a quantitative trait and have implications regarding the mutation-accumulation evolutionary explanation of senescence. PMID:16204222

A Low Protein Diet Increases the Hypoxic Tolerance in Drosophila

PubMed Central

Vigne, Paul; Frelin, Christian

2006-01-01

Dietary restriction is well known to increase the life span of a variety of organisms from yeast to mammals, but the relationships between nutrition and the hypoxic tolerance have not yet been considered. Hypoxia is a major cause of cell death in myocardial infarction and stroke. Here we forced hypoxia-related death by exposing one-day-old male Drosophila to chronic hypoxia (5% O2) and analysed their survival. Chronic hypoxia reduced the average life span from 33.6 days to 6.3 days when flies were fed on a rich diet. A demographic analysis indicated that chronic hypoxia increased the slope of the mortality trajectory and not the short-term risk of death. Dietary restriction produced by food dilution, by yeast restriction, or by amino acid restriction partially reversed the deleterious action of hypoxia. It increased the life span of hypoxic flies up to seven days, which represented about 25% of the life time of an hypoxic fly. Maximum survival of hypoxic flies required only dietary sucrose, and it was insensitive to drugs such as rapamycin and resveratrol, which increase longevity of normoxic animals. The results thus uncover a new link between protein nutrition, nutrient signalling, and resistance to hypoxic stresses. PMID:17183686

Development of "material-specific" hemispheric specialization from beginning to end.

PubMed

Gingras, Benjamin; Braun, Claude M J

2018-07-01

Disparity of verbal and performance intelligence (VIQ, PIQ) on the Wechsler scales of intelligence is a conceptually cluttered and empirically weak measure of hemispheric specialization (HS). However, in the context of life span research, it is the only measure that can be exploited meta-analytically with the lesion method from prenatal life to late senescence. We assembled 1917 cases with a unilateral cortical focal brain lesion occurring at all ages and a post-lesion VIQ and PIQ. Lesion locus, volume and side were documented for each case, as well as age at lesion onset, age at first symptoms and age at the IQ test, presence/absence of epilepsy, lesion aetiology, gender, date of publication or of transfer of medical file. With and without covariate adjustment, HS was significant across the life span though its pattern changed. HS increased linearly and highly significantly until late senescence. Only in early adulthood did VIQ appear to vacate the right temporal lobe and occupy the left and PIQ vacate the left parietal lobe and occupy the right until late senescence. Biomaturational factors are more important in the ontogeny of material-specific HS over the whole life span than previously established.

Rapamycin Increases Mortality in db/db Mice, a Mouse Model of Type 2 Diabetes.

PubMed

Sataranatarajan, Kavithalakshmi; Ikeno, Yuji; Bokov, Alex; Feliers, Denis; Yalamanchili, Himabindu; Lee, Hak Joo; Mariappan, Meenalakshmi M; Tabatabai-Mir, Hooman; Diaz, Vivian; Prasad, Sanjay; Javors, Martin A; Ghosh Choudhury, Goutam; Hubbard, Gene B; Barnes, Jeffrey L; Richardson, Arlan; Kasinath, Balakuntalam S

2016-07-01

We examined the effect of rapamycin on the life span of a mouse model of type 2 diabetes, db/db mice. At 4 months of age, male and female C57BLKSJ-lepr (db/db) mice (db/db) were placed on either a control diet, lacking rapamycin or a diet containing rapamycin and maintained on these diets over their life span. Rapamycin was found to reduce the life span of the db/db mice. The median survival of male db/db mice fed the control and rapamycin diets was 349 and 302 days, respectively, and the median survival of female db/db mice fed the control and rapamycin diets was 487 and 411 days, respectively. Adjusting for gender differences, rapamycin increased the mortality risk 1.7-fold in both male and female db/db mice. End-of-life pathological data showed that suppurative inflammation was the main cause of death in the db/db mice, which is enhanced slightly by rapamycin treatment. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Recent Insights into the HIV/AIDS Pandemic

PubMed Central

Becerra, Juan C.; Bildstein, Lukas S.; Gach, Johannes S.

2016-01-01

Etiology, transmission and protection: Transmission of HIV, the causative agent of AIDS, occurs predominantly through bodily fluids. Factors that significantly alter the risk of HIV transmission include male circumcision, condom use, high viral load, and the presence of other sexually transmitted diseases. Pathology/Symptomatology: HIV infects preferentially CD4+ T lymphocytes, and Monocytes. Because of their central role in regulating the immune response, depletion of CD4+ T cells renders the infected individual incapable of adequately responding to microorganisms otherwise inconsequential. Epidemiology, incidence and prevalence: New HIV infections affect predominantly young heterosexual women and homosexual men. While the mortality rates of AIDS related causes have decreased globally in recent years due to the use of highly active antiretroviral therapy (HAART) treatment, a vaccine remains an elusive goal. Treatment and curability: For those afflicted HIV infection remains a serious illness. Nonetheless, the use of advanced therapeutics have transformed a dire scenario into a chronic condition with near average life spans. When to apply those remedies appears to be as important as the remedies themselves. The high rate of HIV replication and the ability to generate variants are central to the viral survival strategy and major barriers to be overcome. Molecular mechanisms of infection: In this review, we assemble new details on the molecular events from the attachment of the virus, to the assembly and release of the viral progeny. Yet, much remains to be learned as understanding of the molecular mechanisms used in viral replication and the measures engaged in the evasion of immune surveillance will be important to develop effective interventions to address the global HIV pandemic. PMID:28357381

Interim results of quality-control sampling of surface water for the Upper Colorado River National Water-Quality Assessment Study Unit, water years 1995-96

USGS Publications Warehouse

Spahr, N.E.; Boulger, R.W.

1997-01-01

Quality-control samples provide part of the information needed to estimate the bias and variability that result from sample collection, processing, and analysis. Quality-control samples of surface water collected for the Upper Colorado River National Water-Quality Assessment study unit for water years 1995?96 are presented and analyzed in this report. The types of quality-control samples collected include pre-processing split replicates, concurrent replicates, sequential replicates, post-processing split replicates, and field blanks. Analysis of the pre-processing split replicates, concurrent replicates, sequential replicates, and post-processing split replicates is based on differences between analytical results of the environmental samples and analytical results of the quality-control samples. Results of these comparisons indicate that variability introduced by sample collection, processing, and handling is low and will not affect interpretation of the environmental data. The differences for most water-quality constituents is on the order of plus or minus 1 or 2 lowest rounding units. A lowest rounding unit is equivalent to the magnitude of the least significant figure reported for analytical results. The use of lowest rounding units avoids some of the difficulty in comparing differences between pairs of samples when concentrations span orders of magnitude and provides a measure of the practical significance of the effect of variability. Analysis of field-blank quality-control samples indicates that with the exception of chloride and silica, no systematic contamination of samples is apparent. Chloride contamination probably was the result of incomplete rinsing of the dilute cleaning solution from the outlet ports of the decaport sample splitter. Silica contamination seems to have been introduced by the blank water. Sampling and processing procedures for water year 1997 have been modified as a result of these analyses.

Getting older isn’t all that bad: Better decisions and coping when facing ’sunk costs’

PubMed Central

de Bruin, Wändi Bruine; Strough, JoNell; Parker, Andrew M.

2014-01-01

Because people of all ages face decisions that affect their quality of life, decision-making competence is important across the life span. According to theories of rational decision making, one crucial decision skill involves the ability to discontinue failing commitments despite irrecoverable investments also referred to as ‘sunk costs.’ We find that older adults are better than younger adults at making decisions to discontinue such failing commitments especially when irrecoverable losses are large, as well as at coping with the associated irrecoverable losses. Our results are relevant to interventions that aim to promote better decision-making competence across the life span. PMID:25244483

Getting older isn't all that bad: better decisions and coping when facing "sunk costs".

PubMed

Bruine de Bruin, Wändi; Strough, JoNell; Parker, Andrew M

2014-09-01

Because people of all ages face decisions that affect their quality of life, decision-making competence is important across the life span. According to theories of rational decision making, one crucial decision skill involves the ability to discontinue failing commitments despite irrecoverable investments also referred to as "sunk costs." We find that older adults are better than younger adults at making decisions to discontinue such failing commitments especially when irrecoverable losses are large, as well as at coping with the associated irrecoverable losses. Our results are relevant to interventions that aim to promote better decision-making competence across the life span. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Social and demographic correlates of loneliness in late life.

PubMed

Revenson, T A; Johnson, J L

1984-02-01

Although loneliness is often viewed as a serious problem of old age, few studies have addressed either its measurement or prevalence among older populations. The present study analyzed survey data from newspaper questionnaires circulated in three North American cities (N = 2,026) in order to examine the prevalence of loneliness across the life-span and some of its correlates in late life. Loneliness decreased across the adult life-span, with respondents age 65 and older the least lonely; elders were also more satisfied with their social relationships. Neither gender nor living alone was related to loneliness for older people. The data also partially confirm the desolation hypothesis, suggesting that desolation, or the loss of an intimate attachment, rather than isolation per se is a major correlate of loneliness in late life. Further, recency of loss was strongly related to increased loneliness. Directions for future research and intervention are discussed.

Expert Panel Recommendations on Lower Urinary Tract Health of Women Across Their Life Span

PubMed Central

Losada, Liliana; Amundsen, Cindy L.; Ashton-Miller, James; Chai, Toby; Close, Clare; Damaser, Margot; DiSanto, Michael; Dmochowski, Roger; Fraser, Matthew O.; Kielb, Stephanie J.; Kuchel, George; Mueller, Elizabeth R.; Parker-Autry, Candace; Wolfe, Alan J.

2016-01-01

Abstract Urologic and kidney problems are common in women across their life span and affect their daily life, including physical activity, sexual relations, social life, and future health. Urological health in women is still understudied and the underlying mechanisms of female urological dysfunctions are not fully understood. The Society for Women's Health Research (SWHR®) recognized the need to have a roundtable discussion where researchers and clinicians would define the current state of knowledge, gaps, and recommendations for future research directions to transform women's urological health. This report summarizes the discussions, which focused on epidemiology, clinical presentation, basic science, prevention strategies, and efficacy of current therapies. Experts around the table agreed on a set of research, education, and policy recommendations that have the potential to dramatically increase awareness and improve women's urological health at all stages of life. PMID:27285829

How do subvocal rehearsal and general attentional resources contribute to verbal short-term memory span?

PubMed Central

Morra, Sergio

2015-01-01

Whether rehearsal has a causal role in verbal STM has been controversial in the literature. Recent theories of working memory emphasize a role of attentional resources, but leave unclear how they contribute to verbal STM. Two experiments (with 49 and 102 adult participants, respectively) followed up previous studies with children, aiming to clarify the contributions of attentional capacity and rehearsal to verbal STM. Word length and presentation modality were manipulated. Experiment 1 focused on order errors, Experiment 2 on predicting individual differences in span from attentional capacity and articulation rate. Structural equation modeling showed clearly a major role of attentional capacity as a predictor of verbal STM span; but was inconclusive on whether rehearsal efficiency is an additional cause or a consequence of verbal STM. The effects of word length and modality on STM were replicated; a significant interaction was also found, showing a larger modality effect for long than short words, which replicates a previous finding on children. Item errors occurred more often with long words and correlated negatively with articulation rate. This set of findings seems to point to a role of rehearsal in maintaining item information. The probability of order errors per position increased linearly with list length. A revised version of a neo-Piagetian model was fit to the data of Experiment 2. That model was based on two parameters: attentional capacity (independently measured) and a free parameter representing loss of partly-activated information. The model could partly account for the results, but underestimated STM performance of the participants with smaller attentional capacity. It is concluded that modeling of verbal STM should consider individual and developmental differences in attentional capacity, rehearsal rate, and (perhaps) order representation. PMID:25798114

How do subvocal rehearsal and general attentional resources contribute to verbal short-term memory span?

PubMed

Morra, Sergio

2015-01-01

Whether rehearsal has a causal role in verbal STM has been controversial in the literature. Recent theories of working memory emphasize a role of attentional resources, but leave unclear how they contribute to verbal STM. Two experiments (with 49 and 102 adult participants, respectively) followed up previous studies with children, aiming to clarify the contributions of attentional capacity and rehearsal to verbal STM. Word length and presentation modality were manipulated. Experiment 1 focused on order errors, Experiment 2 on predicting individual differences in span from attentional capacity and articulation rate. Structural equation modeling showed clearly a major role of attentional capacity as a predictor of verbal STM span; but was inconclusive on whether rehearsal efficiency is an additional cause or a consequence of verbal STM. The effects of word length and modality on STM were replicated; a significant interaction was also found, showing a larger modality effect for long than short words, which replicates a previous finding on children. Item errors occurred more often with long words and correlated negatively with articulation rate. This set of findings seems to point to a role of rehearsal in maintaining item information. The probability of order errors per position increased linearly with list length. A revised version of a neo-Piagetian model was fit to the data of Experiment 2. That model was based on two parameters: attentional capacity (independently measured) and a free parameter representing loss of partly-activated information. The model could partly account for the results, but underestimated STM performance of the participants with smaller attentional capacity. It is concluded that modeling of verbal STM should consider individual and developmental differences in attentional capacity, rehearsal rate, and (perhaps) order representation.

SUMO1 depletion prevents lipid droplet accumulation and HCV replication.

PubMed

Akil, Abdellah; Wedeh, Ghaith; Zahid Mustafa, Mohammad; Gassama-Diagne, Ama

2016-01-01

Infection by hepatitis C virus (HCV) is a major public-health problem. Chronic infection often leads to cirrhosis, steatosis, and hepatocellular carcinoma. The life cycle of HCV depends on the host cell machinery and involves intimate interaction between viral and host proteins. However, the role of host proteins in the life cycle of HCV remains poorly understood. Here, we identify the small ubiquitin-related modifier (SUMO1) as a key host factor required for HCV replication. We performed a series of cell biology and biochemistry experiments using the HCV JFH-1 (Japanese fulminate hepatitis 1) genotype 2a strain, which produces infectious particles and recapitulates all the steps of the HCV life cycle. We observed that SUMO1 is upregulated in Huh7.5 infected cells. Reciprocally, SUMO1 was found to regulate the expression of viral core protein. Moreover, knockdown of SUMO1 using specific siRNA influenced the accumulation of lipid droplets and reduced HCV replication as measured by qRT-PCR. Thus, we identify SUMO1 as a key host factor required for HCV replication. To our knowledge, this is the first report showing that SUMO1 regulates lipid droplets in the context of viral infection. Our report provides a meaningful insight into how HCV replicates and interacts with host proteins and is of significant importance for the field of HCV and RNA viruses.

Sensitivity of spring phenology to warming across temporal and spatial climate gradients in two independent databases

USGS Publications Warehouse

Cook, Benjamin I.; Wolkovich, Elizabeth M.; Davies, T. Jonathan; Ault, Toby R.; Betancourt, Julio L.; Allen, Jenica M.; Bolmgren, Kjell; Cleland, Elsa E.; Crimmins, Theresa M.; Kraft, Nathan J.B.; Lancaster, Lesley T.; Mazer, Susan J.; McCabe, Gregory J.; McGill, Brian J.; Parmesan, Camille; Pau, Stephanie; Regetz, James; Salamin, Nicolas; Schwartz, Mark D.; Travers, Steven E.

2012-01-01

Disparate ecological datasets are often organized into databases post hoc and then analyzed and interpreted in ways that may diverge from the purposes of the original data collections. Few studies, however, have attempted to quantify how biases inherent in these data (for example, species richness, replication, climate) affect their suitability for addressing broad scientific questions, especially in under-represented systems (for example, deserts, tropical forests) and wild communities. Here, we quantitatively compare the sensitivity of species first flowering and leafing dates to spring warmth in two phenological databases from the Northern Hemisphere. One—PEP725—has high replication within and across sites, but has low species diversity and spans a limited climate gradient. The other—NECTAR—includes many more species and a wider range of climates, but has fewer sites and low replication of species across sites. PEP725, despite low species diversity and relatively low seasonality, accurately captures the magnitude and seasonality of warming responses at climatically similar NECTAR sites, with most species showing earlier phenological events in response to warming. In NECTAR, the prevalence of temperature responders significantly declines with increasing mean annual temperature, a pattern that cannot be detected across the limited climate gradient spanned by the PEP725 flowering and leafing data. Our results showcase broad areas of agreement between the two databases, despite significant differences in species richness and geographic coverage, while also noting areas where including data across broader climate gradients may provide added value. Such comparisons help to identify gaps in our observations and knowledge base that can be addressed by ongoing monitoring and research efforts. Resolving these issues will be critical for improving predictions in understudied and under-sampled systems outside of the temperature seasonal mid-latitudes.

Sensitivity of spring phenology to warming across temporal and spatial climate gradients in two independent databases

NASA Astrophysics Data System (ADS)

Cook, B. I.; Wolkovich, E. M.; Davies, J.; Ault, T. R.; Betancourt, J. L.; Allen, J.; Bolmgren, K.; Cleland, E. E.; Crimmins, T. M.; Kraft, N.; Lancaster, L.; Mazer, S.; McCabe, G. J.; McGill, B.; Parmesan, C.; Pau, S.; Regetz, J.; Salamin, N.; Schwartz, M. D.; Travers, S.

2012-12-01

Disparate ecological datasets are often organized into databases post-hoc and then analyzed and interpreted in ways that may diverge from the purposes of the original data collections. Few studies, however, have attempted to quantify how biases inherent in these data (e.g., species richness, replication, climate) affect their suitability for addressing broad scientific questions, especially in under-represented systems (e.g., deserts, tropical forests) and wild communities. Here, we quantitatively compare the sensitivity of species first flowering and leafing dates to spring warmth in two phenological databases from the Northern Hemisphere. One—PEP725—has high replication within and across sites, but has low species diversity and spans a limited climate gradient. The other—NECTAR—includes many more species and a wider range of climates, but has fewer sites and low replication of species across sites. PEP725, despite low species diversity and relatively low seasonality, accurately captures the magnitude and seasonality of warming responses at climatically similar NECTAR sites, with most species showing earlier phenological events in response to warming. In NECTAR, the prevalence of temperature responders significantly declines with increasing mean annual temperature, a pattern that cannot be detected across the limited climate gradient spanned by the PEP725 flowering and leafing data. Our results showcase broad areas of agreement between the two databases, despite significant differences in species richness and geographic coverage, while also noting areas where including data across broader climate gradients may provide added value. Such comparisons help to identify gaps in our observations and knowledge base that can be addressed by ongoing monitoring and research efforts. Resolving these issues will be critical for improving predictions in understudied and undersampled systems outside of the temperature seasonal midlatitudes.

A virocentric perspective on the evolution of life

PubMed Central

Koonin, Eugene V.; Dolja, Valerian V.

2015-01-01

Viruses and/or virus-like selfish elements are associated with all cellular life forms and are the most abundant biological entities on Earth, with the number of virus particles in many environments exceeding the number of cells by one to two orders of magnitude. The genetic diversity of viruses is commensurately enormous and might substantially exceed the diversity of cellular organisms. Unlike cellular organisms with their uniform replication-expression scheme, viruses possess either RNA or DNA genomes and exploit all conceivable replication-expression strategies. Although viruses extensively exchange genes with their hosts, there exists a set of viral hallmark genes that are shared by extremely diverse groups of viruses to the exclusion of cellular life forms. Coevolution of viruses and host defense systems is a key aspect in the evolution of both viruses and cells, and viral genes are often recruited for cellular functions. Together with the fundamental inevitability of the emergence of genomic parasites in any evolving replicator system, these multiple lines of evidence reveal the central role of viruses in the entire evolution of life. PMID:23850169

Facilitating Career Development through Super's Life Career Rainbow.

ERIC Educational Resources Information Center

Okocha, Aneneosa A.

Super's life-span life-space theory offers a developmental framework for career counseling. This paper provides a brief overview of Super's theory of Life Career Rainbow (LCR) segment. The LCR feature is useful for identifying the stage of a client's career development and in formulating goals for counseling. The assessment is accomplished by…

Integrating Varieties of Life Course Concepts

PubMed Central

2012-01-01

A body of work referred to as the “life course” framework (also known as “life course theory,” the “life course paradigm,” and the “life course perspective”) has been increasingly used to motivate and justify the examination of the relationships among variables in social and behavioral science, particularly in the study of population health and aging. Yet, there is very little agreement on what some of these concepts mean, and there is hardly any agreement on what the “life course” is. This article focuses on the different ways in which the concept of “life course” is used in the contemporary study of aging and human development, particularly with regard to health and well-being. Clarification is given for how “life course” is distinguished from “life span” and “life cycle,” among other “life” words. This work reviews the conceptual literature on the life course, beginning with its formative years in the 1960s and 1970s, through to the present time. Detailed research of several literatures across disciplines revealed five different uses of the term “life course”: (a) life course as time or age, (b) life course as life stages, (c) life course as events, transitions, and trajectories, (d) life course as life-span human development, and (e) life course as early life influences (and their cumulation) on later adult outcomes. To the extent the concept of life course has a multiplicity of meanings that are at variance with one another, this is problematic, as communication is thereby hindered. On the other hand, to the extent the concept of life course involves a rich tapestry of different emphases, this is a good thing, and the diversity of meanings should be retained. This paper proposes a conceptual integration based in part on Riley’s age stratification model that resolves the various meanings of life course into one general framework. Coupled with a demographic conceptualization of the life course, this framework embeds the concept of “life course” within a broader perspective of life-span development. This framework is proposed as an integrated perspective for studying the causes and consequences of “life course events and transitions” and understanding the manner by which “life events” and the role transitions they signify influence the life-span development of outcomes of interest across stages of the life cycle. PMID:22399576

Evolution of Replication Machines

PubMed Central

Yao, Nina Y.; O'Donnell, Mike E.

2016-01-01

The machines that decode and regulate genetic information require the translation, transcription and replication pathways essential to all living cells. Thus, it might be expected that all cells share the same basic machinery for these pathways that were inherited from the primordial ancestor cell from which they evolved. A clear example of this is found in the translation machinery that converts RNA sequence to protein. The translation process requires numerous structural and catalytic RNAs and proteins, the central factors of which are homologous in all three domains of life, bacteria, archaea and eukarya. Likewise, the central actor in transcription, RNA polymerase, shows homology among the catalytic subunits in bacteria, archaea and eukarya. In contrast, while some “gears” of the genome replication machinery are homologous in all domains of life, most components of the replication machine appear to be unrelated between bacteria and those of archaea and eukarya. This review will compare and contrast the central proteins of the “replisome” machines that duplicate DNA in bacteria, archaea and eukarya, with an eye to understanding the issues surrounding the evolution of the DNA replication apparatus. PMID:27160337

Evolution of monogamy, paternal investment, and female life history in Peromyscus.

PubMed

Jašarević, Eldin; Bailey, Drew H; Crossland, Janet P; Dawson, Wallace D; Szalai, Gabor; Ellersieck, Mark R; Rosenfeld, Cheryl S; Geary, David C

2013-02-01

The timing of reproductive development and associated trade-offs in quantity versus quality of offspring produced across the life span are well documented in a wide range of species. The relation of these aspects of maternal life history to monogamy and paternal investment in offspring is not well studied in mammals, due in part to the rarity of the latter. By using five large, captive-bred populations of Peromyscus species that range from promiscuous mating with little paternal investment (P. maniculatus bairdii) to social and genetic monogamy with substantial paternal investment (P. californicus insignis), we modeled the interaction between monogamy and female life history. Monogamy and high paternal investment were associated with smaller litter size, delayed maternal reproduction that extended over a longer reproductive life span, and larger, higher quality offspring. The results suggest monogamy and paternal investment can alter the evolution of female life-history trajectories in mammals. PsycINFO Database Record (c) 2013 APA, all rights reserved

Life-span Socioeconomic Trajectory, Nativity, and Cognitive Aging in Mexican Americans: The Sacramento Area Latino Study on Aging

PubMed Central

Zeki Al-Hazzouri, Adina; Aiello, Allison E.

2011-01-01

Objectives. Early life circumstances influence health across the life span. Migration and ethnicity may modify the lifetime trajectory of socioeconomic status (SES) and lead to heterogeneity in cognitive aging in later life. Methods. We examined the effects of both lifetime socioeconomic trajectory and cumulative disadvantage from childhood through adulthood on late life cognitive performance in a 9-year cohort of 1,789 Mexican Americans aged 60–100 years in 1998–1999. Results. Compared with those with low SES sustained over the life course, we found that those with more advantaged lifetime SES trajectories experienced fewer declines on a test of global cognitive function and a short-term verbal memory test. These associations are larger in first- and second-generation immigrant families. Discussion. Heterogeneity of cognitive aging among diverse race/ethnic groups may be influenced by intergenerational changes in SES, cultural norms, and behaviors and changes in health related to changes in the social and physical environment. PMID:21743044

Life-span socioeconomic trajectory, nativity, and cognitive aging in Mexican Americans: the Sacramento Area Latino Study on Aging.

PubMed

Haan, Mary N; Zeki Al-Hazzouri, Adina; Aiello, Allison E

2011-07-01

Early life circumstances influence health across the life span. Migration and ethnicity may modify the lifetime trajectory of socioeconomic status (SES) and lead to heterogeneity in cognitive aging in later life. We examined the effects of both lifetime socioeconomic trajectory and cumulative disadvantage from childhood through adulthood on late life cognitive performance in a 9-year cohort of 1,789 Mexican Americans aged 60-100 years in 1998-1999. Compared with those with low SES sustained over the life course, we found that those with more advantaged lifetime SES trajectories experienced fewer declines on a test of global cognitive function and a short-term verbal memory test. These associations are larger in first- and second-generation immigrant families. Heterogeneity of cognitive aging among diverse race/ethnic groups may be influenced by intergenerational changes in SES, cultural norms, and behaviors and changes in health related to changes in the social and physical environment.

17. DETAIL OF SOUTH PORTAL, SHOWING "TREE OF LIFE" RAILING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

17. DETAIL OF SOUTH PORTAL, SHOWING "TREE OF LIFE" RAILING DETAIL AS WELL AS BUILDER'S PLATE. - Falls Bridge, Spanning Schuylkill River, connecting East & West River Drives, Philadelphia, Philadelphia County, PA

Modeling the Ebolavirus Life Cycle with Transcription and Replication-Competent Viruslike Particle Assays.

PubMed

Biedenkopf, Nadine; Hoenen, Thomas

2017-01-01

Ebolaviruses are the causative agent of a severe hemorrhagic fever with high case fatality rates, for which no approved specific therapy is available. As biosafety level 4 (BSL4) agents, work with live ebolaviruses is restricted to maximum containment laboratories. Transcription and replication-competent viruslike particle (trVLP) systems are reverse genetics-based life cycle modeling systems that allow researchers to model virtually the entire ebolavirus life cycle outside of a maximum containment laboratory. These systems can be used to dissect the virus life cycle, and thus increase our understanding of virus biology, as well as for more applied uses such as the screening and development of novel antivirals, and thus represent powerful tools for work on ebolaviruses.

Analysis of the temporal program of replication initiation in yeast chromosomes.

PubMed

Friedman, K L; Raghuraman, M K; Fangman, W L; Brewer, B J

1995-01-01

The multiple origins of eukaryotic chromosomes vary in the time of their initiation during S phase. In the chromosomes of Saccharomyces cerevisiae the presence of a functional telomere causes nearby origins to delay initiation until the second half of S phase. The key feature of telomeres that causes the replication delay is the telomeric sequence (C(1-3)A/G(1-3)T) itself and not the proximity of the origin to a DNA end. A second group of late replicating origins has been found at an internal position on chromosome XIV. Four origins, spanning approximately 140 kb, initiate replication in the second half of S phase. At least two of these internal origins maintain their late replication time on circular plasmids. Each of these origins can be separated into two functional elements: those sequences that provide origin function and those that impose late activation. Because the assay for determining replication time is costly and laborious, it has not been possible to analyze in detail these 'late' elements. We report here the development of two new assays for determining replication time. The first exploits the expression of the Escherichia coli dam methylase in yeast and the characteristic period of hemimethylation that transiently follows the passage of a replication fork. The second uses quantitative hybridization to detect two-fold differences in the amount of specific restriction fragments as a function of progress through S phase. The novel aspect of this assay is the creation in vivo of a non-replicating DNA sequence by site-specific pop-out recombination. This non-replicating fragment acts as an internal control for copy number within and between samples. Both of these techniques are rapid and much less costly than the more conventional density transfer experiments that require CsCl gradients to detect replicated DNA. With these techniques it should be possible to identify the sequences responsible for late initiation, to search for other late replicating regions in the genome, and to begin to analyze the effect that altering the temporal program has on chromosome function.

Life Satisfaction, Self-Esteem, and Subjective Age in Women across the Life Span

ERIC Educational Resources Information Center

Borzumato-Gainey, Christine; Kennedy, Alison; McCabe, Beth; Degges-White, Suzanne

2009-01-01

A study of 320 women, ages 21 to 69, explored the relations among relationship status, subjective age, self-esteem, and life satisfaction. Women in married or partnered relationships had higher levels of life satisfaction than did single women. Women in their 30s and 40s had significantly lower levels of life satisfaction than did other age…

Two-carbon metabolites, polyphenols and vitamins influence yeast chronological life span in winemaking conditions

PubMed Central

2012-01-01

Background Viability in a non dividing state is referred to as chronological life span (CLS). Most grape juice fermentation happens when Saccharomyces cerevisiae yeast cells have stopped dividing; therefore, CLS is an important factor toward winemaking success. Results We have studied both the physical and chemical determinants influencing yeast CLS. Low pH and heat shorten the maximum wine yeast life span, while hyperosmotic shock extends it. Ethanol plays an important negative role in aging under winemaking conditions, but additional metabolites produced by fermentative metabolism, such as acetaldehyde and acetate, have also a strong impact on longevity. Grape polyphenols quercetin and resveratrol have negative impacts on CLS under winemaking conditions, an unexpected behavior for these potential anti-oxidants. We observed that quercetin inhibits alcohol and aldehyde dehydrogenase activities, and that resveratrol performs a pro-oxidant role during grape juice fermentation. Vitamins nicotinic acid and nicotinamide are precursors of NAD+, and their addition reduces mean longevity during fermentation, suggesting a metabolic unbalance negative for CLS. Moreover, vitamin mix supplementation at the end of fermentation shortens CLS and enhances cell lysis, while amino acids increase life span. Conclusions Wine S. cerevisiae strains are able to sense changes in the environmental conditions and adapt their longevity to them. Yeast death is influenced by the conditions present at the end of wine fermentation, particularly by the concentration of two-carbon metabolites produced by the fermentative metabolism, such as ethanol, acetic acid and acetaldehyde, and also by the grape juice composition, particularly its vitamin content. PMID:22873488

Normative personality trait development in adulthood: A 6-year cohort-sequential growth model.

PubMed

Milojev, Petar; Sibley, Chris G

2017-03-01

The present study investigated patterns of normative change in personality traits across the adult life span (19 through 74 years of age). We examined change in extraversion, agreeableness, conscientiousness, neuroticism, openness to experience and honesty-humility using data from the first 6 annual waves of the New Zealand Attitudes and Values Study (N = 10,416; 61.1% female, average age = 49.46). We present a cohort-sequential latent growth model assessing patterns of mean-level change due to both aging and cohort effects. Extraversion decreased as people aged, with the most pronounced declines occurring in young adulthood, and then again in old age. Agreeableness, indexed with a measure focusing on empathy, decreased in young adulthood and remained relatively unchanged thereafter. Conscientiousness increased among young adults then leveled off and remained fairly consistent for the rest of the adult life span. Neuroticism and openness to experience decreased as people aged. However, the models suggest that these latter effects may also be partially due to cohort differences, as older people showed lower levels of neuroticism and openness to experience more generally. Honesty-humility showed a pronounced and consistent increase across the adult life span. These analyses of large-scale longitudinal national probability panel data indicate that different dimensions of personality follow distinct developmental processes throughout adulthood. Our findings also highlight the importance of young adulthood (up to about the age of 30) in personality trait development, as well as continuing change throughout the adult life span. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Dietary consumption of monosodium L-glutamate induces adaptive response and reduction in the life span of Drosophila melanogaster.

PubMed

Abolaji, Amos O; Olaiya, Charles O; Oluwadahunsi, Oluwagbenga J; Farombi, Ebenezer O

2017-04-01

Adaptive response is the ability of an organism to better counterattack stress-induced damage in response to a number of different cytotoxic agents. Monosodium L-glutamate (MSG), the sodium salt of amino acid glutamate, is commonly used as a food additive. We investigated the effects of MSG on the life span and antioxidant response in Drosophila melanogaster (D. melanogaster). Both genders (1 to 3 days old) of flies were fed with diet containing MSG (0.1, 0.5, and 2.5-g/kg diet) for 5 days to assess selected antioxidant and oxidative stress markers, while flies for longevity were fed for lifetime. Thereafter, the longevity assay, hydrogen peroxide (H 2 O 2 ), and reactive oxygen and nitrogen species levels were determined. Also, catalase, glutathione S-transferase and acetylcholinesterase activities, and total thiol content were evaluated in the flies. We found that MSG reduced the life span of the flies by up to 23% after continuous exposure. Also, MSG increased reactive oxygen and nitrogen species and H 2 O 2 generations and total thiol content as well as the activities of catalase and glutathione S-transferase in D. melanogaster (P < .05). In conclusion, consumption of MSG for 5 days by D. melanogaster induced adaptive response, but long-term exposure reduced life span of flies. This study may therefore have public health significance in humans, and thus, moderate consumption of MSG is advocated by the authors. Copyright © 2017 John Wiley & Sons, Ltd.

Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms.

PubMed

Patel, Sonal A; Chaudhari, Amol; Gupta, Richa; Velingkaar, Nikkhil; Kondratov, Roman V

2016-04-01

Calorie restriction (CR) increases longevity in many species by unknown mechanisms. The circadian clock was proposed as a potential mediator of CR. Deficiency of the core component of the circadian clock-transcriptional factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1)-results in accelerated aging. Here we investigated the role of BMAL1 in mechanisms of CR. The 30% CR diet increased the life span of wild-type (WT) mice by 20% compared to mice on anad libitum(AL) diet but failed to increase life span ofBmal1(-/-)mice. BMAL1 deficiency impaired CR-mediated changes in the plasma levels of IGF-1 and insulin. We detected a statistically significantly reduction of IGF-1 in CRvs.AL by 50 to 70% in WT mice at several daily time points tested, while inBmal1(-/-)the reduction was not significant. Insulin levels in WT were reduced by 5 to 9%, whileBmal1(-/-)induced it by 10 to 35% at all time points tested. CR up-regulated the daily average expression ofBmal1(by 150%) and its downstream target genesPeriods(by 470% forPer1and by 130% forPer2). We propose that BMAL1 is an important mediator of CR, and activation of BMAL1 might link CR mechanisms with biologic clocks.-Patel, S. A., Chaudhari, A., Gupta, R., Velingkaar, N., Kondratov, R. V. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms. © FASEB.

Physical Activity Throughout the Adult Life Span and Domain-Specific Cognitive Function in Old Age: A Systematic Review of Cross-Sectional and Longitudinal Data.

PubMed

Engeroff, Tobias; Ingmann, Tobias; Banzer, Winfried

2018-06-01

A growing body of literature suggests that physical activity might alleviate the age-related neurodegeneration and decline of cognitive function. However, most of this evidence is based on data investigating the association of exercise interventions or current physical activity behavior with cognitive function in elderly subjects. We performed a systematic review and hypothesize that physical activity during the adult life span is connected with maintained domain-specific cognitive functions during late adulthood defined as age 60+ years. We performed a systematic literature search up to November 2017 in PubMed, Web of Science, and Google Scholar without language limitations for studies analyzing the association of leisure physical activity during the adult life span (age 18+ years) and domain-specific cognitive functions in older adults (age 60+ years). The literature review yielded 14,294 articles and after applying inclusion and exclusion criteria, nine cross-sectional and 14 longitudinal studies were included. Moderate- and vigorous-intensity leisure physical activity was associated with global cognitive function and specific cognitive domains including executive functions and memory but not attention or working memory. Most studies assessed mid- to late-adulthood physical activity, thus information concerning the influence of young adult life-span physical activity is currently lacking. Observational evidence that moderate- and vigorous-intensity leisure physical activity is beneficially associated with maintained cognitive functions during old age is accumulating. Further studies are necessary to confirm a causal link by assessing objective physical activity data and the decline of cognitive functions at multiple time points during old age.

Telomerase-mediated life-span extension of human primary fibroblasts by human artificial chromosome (HAC) vector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shitara, Shingo; Kakeda, Minoru; Nagata, Keiko

2008-05-09

Telomerase-mediated life-span extension enables the expansion of normal cells without malignant transformation, and thus has been thought to be useful in cell therapies. Currently, integrating vectors including the retrovirus are used for human telomerase reverse transcriptase (hTERT)-mediated expansion of normal cells; however, the use of these vectors potentially causes unexpected insertional mutagenesis and/or activation of oncogenes. Here, we established normal human fibroblast (hPF) clones retaining non-integrating human artificial chromosome (HAC) vectors harboring the hTERT expression cassette. In hTERT-HAC/hPF clones, we observed the telomerase activity and the suppression of senescent-associated SA-{beta}-galactosidase activity. Furthermore, the hTERT-HAC/hPF clones continued growing beyond 120 daysmore » after cloning, whereas the hPF clones retaining the silent hTERT-HAC senesced within 70 days. Thus, hTERT-HAC-mediated episomal expression of hTERT allows the extension of the life-span of human primary cells, implying that gene delivery by non-integrating HAC vectors can be used to control cellular proliferative capacity of primary cultured cells.« less

Life-span development of visual working memory: when is feature binding difficult?

PubMed

Cowan, Nelson; Naveh-Benjamin, Moshe; Kilb, Angela; Saults, J Scott

2006-11-01

We asked whether the ability to keep in working memory the binding between a visual object and its spatial location changes with development across the life span more than memory for item information. Paired arrays of colored squares were identical or differed in the color of one square, and in the latter case, the changed color was unique on that trial (item change) or was duplicated elsewhere in the array (color-location binding change). Children (8-10 and 11-12 years old) and older adults (65-85 years old) showed deficits relative to young adults. These were only partly simulated by dividing attention in young adults. The older adults had an additional deficiency, specifically in binding information, which was evident only when item- and binding-change trials were mixed together. In that situation, the older adults often overlooked the more subtle, binding-type changes. Some working memory processes related to binding undergo life-span development in an inverted-U shape, whereas other, bias- and salience-related processes that influence the use of binding information seem to develop monotonically.

Taste bud cell dynamics during normal and sodium-restricted development.

PubMed

Hendricks, Susan J; Brunjes, Peter C; Hill, David L

2004-04-26

Taste bud volume increases over the postnatal period to match the number of neurons providing innervation. To clarify age-related changes in fungiform taste bud volume, the current study investigated developmental changes in taste bud cell number, proliferation rate, and life span. Taste bud growth can largely be accounted for by addition of cytokeratin-19-positive taste bud cells. Examination of taste bud cell kinetics with 3H-thymidine autoradiography revealed that cell life span and turnover periods were not altered during normal development but that cells were produced more rapidly in young rats, a prominent modification that could lead to increased taste bud size. By comparison, dietary sodium restriction instituted during pre- and postnatal development results in small taste buds at adulthood as a result of fewer cytokeratin-19-positive cells. The dietary manipulation also had profound influences on taste bud growth kinetics, including an increased latency for cells to enter the taste bud and longer life span and turnover periods. These studies provide fundamental, new information about taste bud development under normal conditions and after environmental manipulations that impact nerve/target matching. Copyright 2004 Wiley-Liss, Inc.

Lung glutathione reductase induction in aging catalase-depleted frogs correlates with early survival throughout the life span.

PubMed

Perez-Campo, R; Lopez-Torres, M; Rojas, C; Cadenas, S; Barja de Quiroga, G

1993-02-01

A comprehensive experimental study on free radical-related parameters was performed in the lung throughout the life span of 220 initially young or old frogs. No age related differences were found transversely or longitudinally for lung superoxide dismutase, catalase, Se-dependent and -independent glutathione peroxidases, glutathione reductase, GSH, GSSG, or GSSG/GSH ratio. Continuous catalase depletion with aminotriazole led to glutathione reductase induction in the lung after 14.5 months of experimentation. This was accompanied by a great increase in survival rate of treated animals in relation to controls (especially in the old group). After 26.5 months of experimentation, glutathione reductase induction was lost and GSSG/GSH values tended to increase. This was followed by a 3-month long period of acute decrease in survival rate of treated animals. It is suggested that a high antioxidant/prooxidant balance is of protective value against causes of early death and can possibly be used in the future (when appropriately controlled) to increase the number of healthy years of the normal life span.

Age trends for failures of sustained attention.

PubMed

Carriere, Jonathan S A; Cheyne, J Allan; Solman, Grayden J F; Smilek, Daniel

2010-09-01

Recent research has revealed an age-related reduction in errors in a sustained attention task, suggesting that sustained attention abilities improve with age. Such results seem paradoxical in light of the well-documented age-related declines in cognitive performance. In the present study, performance on the sustained attention to response task (SART) was assessed in a supplemented archival sample of 638 individuals between 14 and 77 years old. SART errors and response speed appeared to decline in a linear fashion as a function of age throughout the age span studied. In contrast, other measures of sustained attention (reaction time coefficient of variation), anticipation, and omissions) showed a decrease early in life and then remained unchanged for the rest of the life span. Thus, sustained attention shows improvements with maturation in early adulthood but then does not change with aging in older adults. On the other hand, aging across the entire life span leads to a more strategic (i.e., slower) response style that reduces the overt and critical consequences (i.e., SART errors) of momentary task disengagement. (c) 2010 APA, all rights reserved.

Does telomere elongation lead to a longer lifespan if cancer is considered?

NASA Astrophysics Data System (ADS)

Masa, Michael; Cebrat, Stanisław; Stauffer, Dietrich

2006-05-01

As cell proliferation is limited due to the loss of telomere repeats in DNA of normal somatic cells during division, telomere attrition can possibly play an important role in determining the maximum life span of organisms as well as contribute to the process of biological ageing. With computer simulations of cell culture development in organisms, which consist of tissues of normal somatic cells with finite growth, we obtain an increase of life span and life expectancy for longer telomeric DNA in the zygote. By additionally considering a two-mutation model for carcinogenesis and indefinite proliferation by the activation of telomerase, we demonstrate that the risk of dying due to cancer can outweigh the positive effect of longer telomeres on the longevity.

Shaping the Flavivirus Replication Complex: It's Curvaceous!

PubMed

Aktepe, Turgut E; Mackenzie, Jason M

2018-06-22

Flavivirus replication is intimately involved with remodelled membrane organelles that are compartmentalised for different functions during their life cycle. Recent advances in lipid analyses and gene depletion have identified a number of host components that enable efficient virus replication in infected cells. Here we describe the current understanding on the role and contribution of host lipids and membrane bending proteins to flavivirus replication, with a particular focus on the components that bend and shape the membrane bilayer to induce the flavivirus-induced organelles characteristic of infection. This article is protected by copyright. All rights reserved.

The Effects of Role Congruence and Role Conflict on Work, Marital, and Life Satisfaction

ERIC Educational Resources Information Center

Perrone, Kristin M.; Webb, L. Kay; Blalock, Rachel H.

2005-01-01

The impact of role congruence and role conflict on work, marital, and life satisfaction was studied using Super's life-span, life-space theory. A conceptual model of relationships between these variables was proposed, and gender differences were examined. Participants were 35 male and 60 female college graduates who completed surveys by mail.…

Chromatin Heterogeneity and Distribution of Regulatory Elements in the Late-Replicating Intercalary Heterochromatin Domains of Drosophila melanogaster Chromosomes

PubMed Central

Khoroshko, Varvara A.; Levitsky, Viktor G.; Zykova, Tatyana Yu.; Antonenko, Oksana V.; Belyaeva, Elena S.; Zhimulev, Igor F.

2016-01-01

Late-replicating domains (intercalary heterochromatin) in the Drosophila genome display a number of features suggesting their organization is quite unique. Typically, they are quite large and encompass clusters of functionally unrelated tissue-specific genes. They correspond to the topologically associating domains and conserved microsynteny blocks. Our study aims at exploring further details of molecular organization of intercalary heterochromatin and has uncovered surprising heterogeneity of chromatin composition in these regions. Using the 4HMM model developed in our group earlier, intercalary heterochromatin regions were found to host chromatin fragments with a particular epigenetic profile. Aquamarine chromatin fragments (spanning 0.67% of late-replicating regions) are characterized as a class of sequences that appear heterogeneous in terms of their decompactization. These fragments are enriched with enhancer sequences and binding sites for insulator proteins. They likely mark the chromatin state that is related to the binding of cis-regulatory proteins. Malachite chromatin fragments (11% of late-replicating regions) appear to function as universal transitional regions between two contrasting chromatin states. Namely, they invariably delimit intercalary heterochromatin regions from the adjacent active chromatin of interbands. Malachite fragments also flank aquamarine fragments embedded in the repressed chromatin of late-replicating regions. Significant enrichment of insulator proteins CP190, SU(HW), and MOD2.2 was observed in malachite chromatin. Neither aquamarine nor malachite chromatin types appear to correlate with the positions of highly conserved non-coding elements (HCNE) that are typically replete in intercalary heterochromatin. Malachite chromatin found on the flanks of intercalary heterochromatin regions tends to replicate earlier than the malachite chromatin embedded in intercalary heterochromatin. In other words, there exists a gradient of replication progressing from the flanks of intercalary heterochromatin regions center-wise. The peculiar organization and features of replication in large late-replicating regions are discussed as possible factors shaping the evolutionary stability of intercalary heterochromatin. PMID:27300486

14 CFR 170.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... approach control service. Arrival means any aircraft arriving at an airport. Benefit-cost ratio means the... (i.e., ATCT) divided by the discounted life cycle costs. Ceiling means the vertical distance between... to aviation users over the life span of a facility or service. Life cycle costs means the value of...

14 CFR 170.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... approach control service. Arrival means any aircraft arriving at an airport. Benefit-cost ratio means the... (i.e., ATCT) divided by the discounted life cycle costs. Ceiling means the vertical distance between... to aviation users over the life span of a facility or service. Life cycle costs means the value of...

14 CFR 170.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... approach control service. Arrival means any aircraft arriving at an airport. Benefit-cost ratio means the... (i.e., ATCT) divided by the discounted life cycle costs. Ceiling means the vertical distance between... to aviation users over the life span of a facility or service. Life cycle costs means the value of...

14 CFR 170.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... approach control service. Arrival means any aircraft arriving at an airport. Benefit-cost ratio means the... (i.e., ATCT) divided by the discounted life cycle costs. Ceiling means the vertical distance between... to aviation users over the life span of a facility or service. Life cycle costs means the value of...

The Balancing Act of Adult Life. ERIC Digest.

ERIC Educational Resources Information Center

Kerka, Sandra

Life is more complex than ever for adults in the 21st century as a result of technological advances; the changing nature of work, workplaces, and working relationships; international economic competition; the changing demographics of workers, families, and communities; and longer life spans. Learning to cope with all these changing…

Contributing to Overall Life Satisfaction: Personality Traits Versus Life Satisfaction Variables Revisited—Is Replication Impossible?

PubMed Central

Lachmann, Bernd; Sariyska, Rayna; Kannen, Christopher; Błaszkiewicz, Konrad; Trendafilov, Boris; Andone, Ionut; Eibes, Mark; Markowetz, Alexander; Li, Mei; Kendrick, Keith M.

2017-01-01

Virtually everybody would agree that life satisfaction is of immense importance in everyday life. Thus, it is not surprising that a considerable amount of research using many different methodological approaches has investigated what the best predictors of life satisfaction are. In the present study, we have focused on several key potential influences on life satisfaction including bottom-up and top-down models, cross-cultural effects, and demographic variables. In four independent (large scale) surveys with sample sizes ranging from N = 488 to 40,297, we examined the associations between life satisfaction and various related variables. Our findings demonstrate that prediction of overall life satisfaction works best when including information about specific life satisfaction variables. From this perspective, satisfaction with leisure showed the highest impact on overall life satisfaction in our European samples. Personality was also robustly associated with life satisfaction, but only when life satisfaction variables were not included in the regression model. These findings could be replicated in all four independent samples, but it was also demonstrated that the relevance of life satisfaction variables changed under the influence of cross-cultural effects. PMID:29295529

Distribution of the anther-smut pathogen Microbotryum on species of the Caryophyllaceae

PubMed Central

Hood, Michael E; Mena-Alí, Jorge I; Gibson, Amanda K; Oxelman, Bengt; Giraud, Tatiana; Yockteng, Roxana; Arroyo, Mary T K; Conti, Fabio; Pedersen, Amy B; Gladieux, Pierre; Antonovics, Janis

2010-01-01

Summary Understanding disease distributions is of fundamental and applied importance, yet few studies benefit from integrating broad sampling with ecological and phylogenetic data. Here, anther-smut disease, caused by the fungus Microbotryum, was assessed using herbarium specimens of Silene and allied genera of the Caryophyllaceae.A total of 42 000 herbarium specimens were examined, and plant geographical distributions and morphological and life history characteristics were tested as correlates of disease occurrence. Phylogenetic comparative methods were used to determine the association between disease and plant life-span.Disease was found on 391 herbarium specimens from 114 species and all continents with native Silene. Anther smut occurred exclusively on perennial plants, consistent with the pathogen requiring living hosts to overwinter. The disease was estimated to occur in 80% of perennial species of Silene and allied genera. The correlation between plant life-span and disease was highly significant while controlling for the plant phylogeny, but the disease was not correlated with differences in floral morphology.Using resources available in natural history collections, this study illustrates how disease distribution can be determined, not by restriction to a clade of susceptible hosts or to a limited geographical region, but by association with host life-span, a trait that has undergone frequent evolutionary transitions. PMID:20406409

Thrombokinetics in patients with rheumatoid arthritis treated with D-penicillamine.

PubMed Central

Thomas, D; Gallus, A S; Brooks, P M; Tampi, R; Geddes, R; Hill, W

1984-01-01

The mechanism of D-penicillamine induced thrombocytopenia in rheumatoid arthritis was investigated by measuring platelet life-span and platelet production rate in 2 groups of rheumatoid arthritis patients treated with 250-750 mg/day D-penicillamine, 14 with a normal platelet count and 9 with thrombocytopenia (platelet count 50-130 X 10(9)/1). Age matched control patients not treated with D-penicillamine included 14 with rheumatoid arthritis and 9 with osteoarthritis. The platelet life-span was normal, but platelet production rate was significantly reduced in the thrombocytopenic patients, suggesting that D-penicillamine causes thrombocytopenia through bone marrow suppression. PMID:6742902

[Immunogenicity of L5178Y cells modified by different reagents].

PubMed

Gómez-Estrada, H; López-de la Rosa, L M; Becerril-Meza, G; Arellano-Blanco, J; Fernández-Quintero, P

1977-01-01

Lymphoma L5178Y cells were treated with neuraminidase of Vibrio cholerae, potassium iodine, dithiotreitol (DTT), mercaptoethanol, glutaraldehyde, iodoacetamide, merthiolate, sodium periodate, urea, papaine, trypsine and EDTA, to increase immunoreaction in tumor cells. Mice were immunized with modified tumor cells every week for one month. Thereafter non modified tumor cells were transplanted to previously immunized mice. Only the immunization with neuraminidase-treated cells rejected the tumor. Although the immunization with cells treated with potassium iodine, DTT and mercaptoethanol did not reject tumor, prolonged significantly span of life. The other reactives had neither effect on tumor rejection nor on span of life.

Reproductive potential and instability of the rDNA region of the Saccharomyces cerevisiae yeast: Common or separate mechanisms of regulation?

PubMed

Zadrag-Tecza, Renata; Skoneczna, Adrianna

2016-11-01

The yeast Saccharomyces cerevisiae is a unicellular organism commonly used as a model to explain mechanisms of aging in multicellular organisms. It is used as a model organism for both replicative and chronological aging. Replicative aging is defined as the number of daughter cells produced by an individual cell during its life. A widely accepted hypothesis assumes that replicative aging of yeast is related to the existence of a so called "senescence factor" that gradually accumulates in the mother cell, which consequently leads to its death. One of the earliest proposed "senescence factors" were extrachromosomal rDNA circles (ERCs). However, their role in the regulation of the replicative lifespan is somewhat controversial and subject to discussion. In this paper, we propose a more comprehensive approach to this problem by analysing the length of life and the correlation between the cell size and the replicative lifespan of yeast cells with different level of ERCs, i.e. Δrad52 and Δsgs1 mutants. This analysis shows that it is not the accumulation of ERCs but genomic instability and hypertrophy that play an important role in the regulation of reproductive potential and total lifespan of the S. cerevisiae yeast. However, these two factors have a different impact on various phases of the yeast cell life, i.e. reproductive and post-reproductive phases. Copyright © 2016 Elsevier Inc. All rights reserved.

Hard-Earned Wisdom: Exploratory Processing of Difficult Life Experience Is Positively Associated with Wisdom

ERIC Educational Resources Information Center

Weststrate, Nic M.; Glück, Judith

2017-01-01

Laypersons and experts believe that wisdom is cultivated through a diverse range of positive and negative life experiences. Yet, not all individuals with life experience are wise. We propose that one possible determinant of growth in wisdom from life experience is self-reflection. In a life span sample of adults (N = 94) ranging from 26 to 92…

Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at the Level of Virus Entry and at a Late Stage in the Virus Life Cycle

PubMed Central

Londrigan, Sarah L.; Short, Kirsty R.; Ma, Joel; Gillespie, Leah; Rockman, Steven P.; Brooks, Andrew G.

2015-01-01

ABSTRACT Airway epithelial cells are susceptible to infection with seasonal influenza A viruses (IAV), resulting in productive virus replication and release. Macrophages (MΦ) are also permissive to IAV infection; however, virus replication is abortive. Currently, it is unclear how productive infection of MΦ is impaired or the extent to which seasonal IAV replicate in MΦ. Herein, we compared mouse MΦ and epithelial cells for their ability to support genomic replication and transcription, synthesis of viral proteins, assembly of virions, and release of infectious progeny following exposure to genetically defined IAV. We confirm that seasonal IAV differ in their ability to utilize cell surface receptors for infectious entry and that this represents one level of virus restriction. Following virus entry, we demonstrate synthesis of all eight segments of genomic viral RNA (vRNA) and mRNA, as well as seven distinct IAV proteins, in IAV-infected mouse MΦ. Although newly synthesized hemagglutinin (HA) and neuraminidase (NA) glycoproteins are incorporated into the plasma membrane and expressed at the cell surface, electron microscopy confirmed that virus assembly was defective in IAV-infected MΦ, defining a second level of restriction late in the virus life cycle. IMPORTANCE Seasonal influenza A viruses (IAV) and highly pathogenic avian influenza viruses (HPAI) infect macrophages, but only HPAI replicate productively in these cells. Herein, we demonstrate that impaired virus uptake into macrophages represents one level of restriction limiting infection by seasonal IAV. Following uptake, seasonal IAV do not complete productive replication in macrophages, representing a second level of restriction. Using murine macrophages, we demonstrate that productive infection is blocked late in the virus life cycle, such that virus assembly is defective and newly synthesized virions are not released. These studies represent an important step toward identifying host-encoded factors that block replication of seasonal IAV, but not HPAI, in macrophages. PMID:26423941

Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at the Level of Virus Entry and at a Late Stage in the Virus Life Cycle.

PubMed

Londrigan, Sarah L; Short, Kirsty R; Ma, Joel; Gillespie, Leah; Rockman, Steven P; Brooks, Andrew G; Reading, Patrick C

2015-12-01

Airway epithelial cells are susceptible to infection with seasonal influenza A viruses (IAV), resulting in productive virus replication and release. Macrophages (MΦ) are also permissive to IAV infection; however, virus replication is abortive. Currently, it is unclear how productive infection of MΦ is impaired or the extent to which seasonal IAV replicate in MΦ. Herein, we compared mouse MΦ and epithelial cells for their ability to support genomic replication and transcription, synthesis of viral proteins, assembly of virions, and release of infectious progeny following exposure to genetically defined IAV. We confirm that seasonal IAV differ in their ability to utilize cell surface receptors for infectious entry and that this represents one level of virus restriction. Following virus entry, we demonstrate synthesis of all eight segments of genomic viral RNA (vRNA) and mRNA, as well as seven distinct IAV proteins, in IAV-infected mouse MΦ. Although newly synthesized hemagglutinin (HA) and neuraminidase (NA) glycoproteins are incorporated into the plasma membrane and expressed at the cell surface, electron microscopy confirmed that virus assembly was defective in IAV-infected MΦ, defining a second level of restriction late in the virus life cycle. Seasonal influenza A viruses (IAV) and highly pathogenic avian influenza viruses (HPAI) infect macrophages, but only HPAI replicate productively in these cells. Herein, we demonstrate that impaired virus uptake into macrophages represents one level of restriction limiting infection by seasonal IAV. Following uptake, seasonal IAV do not complete productive replication in macrophages, representing a second level of restriction. Using murine macrophages, we demonstrate that productive infection is blocked late in the virus life cycle, such that virus assembly is defective and newly synthesized virions are not released. These studies represent an important step toward identifying host-encoded factors that block replication of seasonal IAV, but not HPAI, in macrophages. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Reactivation and Lytic Replication of Kaposi’s Sarcoma-Associated Herpesvirus: An Update

PubMed Central

Aneja, Kawalpreet K.; Yuan, Yan

2017-01-01

The life cycle of Kaposi’s sarcoma-associated herpesvirus (KSHV) consists of two phases, latent and lytic. The virus establishes latency as a strategy for avoiding host immune surveillance and fusing symbiotically with the host for lifetime persistent infection. However, latency can be disrupted and KSHV is reactivated for entry into the lytic replication. Viral lytic replication is crucial for efficient dissemination from its long-term reservoir to the sites of disease and for the spread of the virus to new hosts. The balance of these two phases in the KSHV life cycle is important for both the virus and the host and control of the switch between these two phases is extremely complex. Various environmental factors such as oxidative stress, hypoxia, and certain chemicals have been shown to switch KSHV from latency to lytic reactivation. Immunosuppression, unbalanced inflammatory cytokines, and other viral co-infections also lead to the reactivation of KSHV. This review article summarizes the current understanding of the initiation and regulation of KSHV reactivation and the mechanisms underlying the process of viral lytic replication. In particular, the central role of an immediate-early gene product RTA in KSHV reactivation has been extensively investigated. These studies revealed multiple layers of regulation in activation of RTA as well as the multifunctional roles of RTA in the lytic replication cascade. Epigenetic regulation is known as a critical layer of control for the switch of KSHV between latency and lytic replication. The viral non-coding RNA, PAN, was demonstrated to play a central role in the epigenetic regulation by serving as a guide RNA that brought chromatin remodeling enzymes to the promoters of RTA and other lytic genes. In addition, a novel dimension of regulation by microPeptides emerged and has been shown to regulate RTA expression at the protein level. Overall, extensive investigation of KSHV reactivation and lytic replication has revealed a sophisticated regulation network that controls the important events in KSHV life cycle. PMID:28473805

Characterization of the catalytic center of the Ebola virus L polymerase.

PubMed

Schmidt, Marie Luisa; Hoenen, Thomas

2017-10-01

Ebola virus (EBOV) causes a severe hemorrhagic fever in humans and non-human primates. While no licensed therapeutics are available, recently there has been tremendous progress in developing antivirals. Targeting the ribonucleoprotein complex (RNP) proteins, which facilitate genome replication and transcription, and particularly the polymerase L, is a promising antiviral approach since these processes are essential for the virus life cycle. However, until now little is known about L in terms of its structure and function, and in particular the catalytic center of the RNA-dependent RNA polymerase (RdRp) of L, which is one of the most promising molecular targets, has never been experimentally characterized. Using multiple sequence alignments with other negative sense single-stranded RNA viruses we identified the putative catalytic center of the EBOV RdRp. An L protein with mutations in this center was then generated and characterized using various life cycle modelling systems. These systems are based on minigenomes, i.e. miniature versions of the viral genome, in which the viral genes are exchanged against a reporter gene. When such minigenomes are coexpressed with RNP proteins in mammalian cells, the RNP proteins recognize them as authentic templates for replication and transcription, resulting in reporter activity reflecting these processes. Replication-competent minigenome systems indicated that our L catalytic domain mutant was impaired in genome replication and/or transcription, and by using replication-deficient minigenome systems, as well as a novel RT-qPCR-based genome replication assay, we showed that it indeed no longer supported either of these processes. However, it still showed similar expression to wild-type L, and retained its ability to be incorporated into inclusion bodies, which are the sites of EBOV genome replication. We have experimentally defined the catalytic center of the EBOV RdRp, and thus a promising antiviral target regulating an essential aspect of the EBOV life cycle.

Noise-induced symmetry breaking far from equilibrium and the emergence of biological homochirality

NASA Astrophysics Data System (ADS)

Jafarpour, Farshid; Biancalani, Tommaso; Goldenfeld, Nigel

2017-03-01

The origin of homochirality, the observed single-handedness of biological amino acids and sugars, has long been attributed to autocatalysis, a frequently assumed precursor for early life self-replication. However, the stability of homochiral states in deterministic autocatalytic systems relies on cross-inhibition of the two chiral states, an unlikely scenario for early life self-replicators. Here we present a theory for a stochastic individual-level model of autocatalytic prebiotic self-replicators that are maintained out of thermal equilibrium. Without chiral inhibition, the racemic state is the global attractor of the deterministic dynamics, but intrinsic multiplicative noise stabilizes the homochiral states. Moreover, we show that this noise-induced bistability is robust with respect to diffusion of molecules of opposite chirality, and systems of diffusively coupled autocatalytic chemical reactions synchronize their final homochiral states when the self-replication is the dominant production mechanism for the chiral molecules. We conclude that nonequilibrium autocatalysis is a viable mechanism for homochirality, without imposing additional nonlinearities such as chiral inhibition.

YAP controls retinal stem cell DNA replication timing and genomic stability

PubMed Central

Cabochette, Pauline; Vega-Lopez, Guillermo; Bitard, Juliette; Parain, Karine; Chemouny, Romain; Masson, Christel; Borday, Caroline; Hedderich, Marie; Henningfeld, Kristine A; Locker, Morgane; Bronchain, Odile; Perron, Muriel

2015-01-01

The adult frog retina retains a reservoir of active neural stem cells that contribute to continuous eye growth throughout life. We found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in these stem cells. Yap knock-down leads to an accelerated S-phase and an abnormal progression of DNA replication, a phenotype likely mediated by upregulation of c-Myc. This is associated with an increased occurrence of DNA damage and eventually p53-p21 pathway-mediated cell death. Finally, we identified PKNOX1, a transcription factor involved in the maintenance of genomic stability, as a functional and physical interactant of YAP. Altogether, we propose that YAP is required in adult retinal stem cells to regulate the temporal firing of replication origins and quality control of replicated DNA. Our data reinforce the view that specific mechanisms dedicated to S-phase control are at work in stem cells to protect them from genomic instability. DOI: http://dx.doi.org/10.7554/eLife.08488.001 PMID:26393999

Royal Jelly-Mediated Prolongevity and Stress Resistance in Caenorhabditis elegans Is Possibly Modulated by the Interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3 Proteins.

PubMed

Wang, Xiaoxia; Cook, Lauren F; Grasso, Lindsay M; Cao, Min; Dong, Yuqing

2015-07-01

Recent studies suggest that royal jelly (RJ) and its related substances may have antiaging properties. However, the molecular mechanisms underlying the beneficial effects remain elusive. We report that the effects of RJ and enzyme-treated RJ (eRJ) on life span and health span in Caenorhabditis elegans (C elegans) are modulated by the sophisticated interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3 proteins. Dietary supplementation with RJ or eRJ increased C. elegans life span in a dose-dependent manner. The RJ and eRJ consumption increased the tolerance of C elegans to oxidative stress, ultraviolet irradiation, and heat shock stress. Our genetic analyses showed that RJ/eRJ-mediated life-span extension requires insulin/IGF-1 signaling and the activities of DAF-16, SIR-2.1, HCF-1, and FTT-2, a 14-3-3 protein. Earlier studies reported that DAF-16/FOXO, SIR-2.1/SIRT1, FTT-2, and HCF-1 have extensive interplays in worms and mammals. Our present findings suggest that RJ/eRJ-mediated promotion of longevity and stress resistance in C elegans is dependent on these conserved interplays. From an evolutionary point of view, this study not only provides new insights into the molecular mechanisms of RJ's action on health span promotion in C elegans, but also has imperative implications in using RJ/eRJ as nutraceuticals to delay aging and age-related disorders. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

VIV analysis of pipelines under complex span conditions

NASA Astrophysics Data System (ADS)

Wang, James; Steven Wang, F.; Duan, Gang; Jukes, Paul

2009-06-01

Spans occur when a pipeline is laid on a rough undulating seabed or when upheaval buckling occurs due to constrained thermal expansion. This not only results in static and dynamic loads on the flowline at span sections, but also generates vortex induced vibration (VIV), which can lead to fatigue issues. The phenomenon, if not predicted and controlled properly, will negatively affect pipeline integrity, leading to expensive remediation and intervention work. Span analysis can be complicated by: long span lengths, a large number of spans caused by a rough seabed, and multi-span interactions. In addition, the complexity can be more onerous and challenging when soil uncertainty, concrete degradation and unknown residual lay tension are considered in the analysis. This paper describes the latest developments and a ‘state-of-the-art’ finite element analysis program that has been developed to simulate the span response of a flowline under complex boundary and loading conditions. Both VIV and direct wave loading are captured in the analysis and the results are sequentially used for the ultimate limit state (ULS) check and fatigue life calculation.

Integrating the pace-of-life syndrome across species, sexes and individuals: covariation of life history and personality under pesticide exposure.

PubMed

Debecker, Sara; Sanmartín-Villar, Iago; de Guinea-Luengo, Miguel; Cordero-Rivera, Adolfo; Stoks, Robby

2016-05-01

The pace-of-life syndrome (POLS) hypothesis integrates covariation of life-history traits along a fast-slow continuum and covariation of behavioural traits along a proactive-reactive personality continuum. Few studies have investigated these predicted life-history/personality associations among species and between sexes. Furthermore, whether and how contaminants interfere with POLS patterns remains unexplored. We tested for covariation patterns in life history and in behaviour, and for life-history/personality covariation among species, among individuals within species and between sexes. Moreover, we investigated whether pesticide exposure affects covariation between life history and behaviour and whether species and sexes with a faster POLS strategy have a higher sensitivity to pesticides. We reared larvae of four species of Ischnura damselflies in a common garden experiment with an insecticide treatment (chlorpyrifos absent/present) in the final instar. We measured four life-history traits (larval growth rate during the pesticide treatment, larval development time, adult mass and life span) and two behavioural traits (larval feeding activity and boldness, each before and after the pesticide treatment). At the individual level, life-history traits and behavioural traits aligned along a fast-slow and a proactive-reactive continuum, respectively. Species-specific differences in life history, with fast-lived species having a faster larval growth and development, a lower mass at emergence and a shorter life span, suggested that time constraints in the larval stage were predictably driving life-history evolution both in the larval stage and across metamorphosis in the adult stage. Across species, females were consistently more slow-lived than males, reflecting that a large body size and a long life span are generally more important for females. In contrast to the POLS hypothesis, there was only little evidence for the expected positive coupling between life-history pace and proactivity. Pesticide exposure decreased larval growth rate and affected life-history/personality covariation in the most fast-lived species. Our study supports the existence of life-history and behavioural continua with limited support for life-history/personality covariation. Variation in digestive physiology may explain this decoupling of life history and behaviour and provide valuable mechanistic insights to understand and predict the occurrence of life-history/personality covariation patterns. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

Listening Niches across a Century of Popular Music

PubMed Central

Krumhansl, Carol Lynne

2017-01-01

This article investigates the contexts, or “listening niches”, in which people hear popular music. The study spanned a century of popular music, divided into 10 decades, with participants born between 1940 and 1999. It asks about whether they know and like the music in each decade, and their emotional reactions. It also asks whether the music is associated with personal memories and, if so, with whom they were listening, or whether they were listening alone. Finally, it asks what styles of music they were listening to, and the music media they were listening with, in different periods of their lives. The results show a regular progression through the life span of listening with different individuals (from parents to children) and with different media (from records to streaming services). A number of effects found in previous studies were replicated, but the study also showed differences across the birth cohorts. Overall, there was a song specific age effect with preferences for music of late adolescence and early adulthood; however, this effect was stronger for the older participants. In general, music of the 1940s, 1960s, and 1980s was preferred, particularly among younger participants. Music of these decades also produced the strongest emotional responses, and the most frequent and specific personal memories. When growing up, the participants tended to listen to the older music on the older media, but rapidly shifted to the new music technologies in their late teens and early 20s. Younger listeners are currently listening less to music alone than older listeners, suggesting an important role of socially sharing music, but they also report feeling sadder when listening to music. Finally, the oldest listeners had the broadest taste, liking music that they had been exposed to during their lifetimes in different listening niches. PMID:28424637

Listening Niches across a Century of Popular Music.

PubMed

Krumhansl, Carol Lynne

2017-01-01

This article investigates the contexts, or "listening niches", in which people hear popular music. The study spanned a century of popular music, divided into 10 decades, with participants born between 1940 and 1999. It asks about whether they know and like the music in each decade, and their emotional reactions. It also asks whether the music is associated with personal memories and, if so, with whom they were listening, or whether they were listening alone. Finally, it asks what styles of music they were listening to, and the music media they were listening with, in different periods of their lives. The results show a regular progression through the life span of listening with different individuals (from parents to children) and with different media (from records to streaming services). A number of effects found in previous studies were replicated, but the study also showed differences across the birth cohorts. Overall, there was a song specific age effect with preferences for music of late adolescence and early adulthood; however, this effect was stronger for the older participants. In general, music of the 1940s, 1960s, and 1980s was preferred, particularly among younger participants. Music of these decades also produced the strongest emotional responses, and the most frequent and specific personal memories. When growing up, the participants tended to listen to the older music on the older media, but rapidly shifted to the new music technologies in their late teens and early 20s. Younger listeners are currently listening less to music alone than older listeners, suggesting an important role of socially sharing music, but they also report feeling sadder when listening to music. Finally, the oldest listeners had the broadest taste, liking music that they had been exposed to during their lifetimes in different listening niches.

Live cell imaging of the HIV-1 life cycle

PubMed Central

Campbell, Edward M.; Hope, Thomas J.

2010-01-01

Technology developed in the past 10 years has dramatically increased the ability of researchers to directly visualize and measure various stages of the HIV type 1 (HIV-1) life cycle. In many cases, imaging-based approaches have filled critical gaps in our understanding of how certain aspects of viral replication occur in cells. Specifically, live cell imaging has allowed a better understanding of dynamic, transient events that occur during HIV-1 replication, including the steps involved in viral fusion, trafficking of the viral nucleoprotein complex in the cytoplasm and even the nucleus during infection and the formation of new virions from an infected cell. In this review, we discuss how researchers have exploited fluorescent microscopy methodologies to observe and quantify these events occurring during the replication of HIV-1 in living cells. PMID:18977142

The Origins of the RNA World

PubMed Central

Robertson, Michael P; Joyce, Gerald F

2012-01-01

The general notion of an “RNA World” is that, in the early development of life on the Earth, genetic continuity was assured by the replication of RNA and genetically encoded proteins were not involved as catalysts. There is now strong evidence indicating that an RNA World did indeed exist before DNA- and protein-based life. However, arguments regarding whether life on Earth began with RNA are more tenuous. It might be imagined that all of the components of RNA were available in some prebiotic pool, and that these components assembled into replicating, evolving polynucleotides without the prior existence of any evolved macromolecules. A thorough consideration of this “RNA-first” view of the origin of life must reconcile concerns regarding the intractable mixtures that are obtained in experiments designed to simulate the chemistry of the primitive Earth. Perhaps these concerns will eventually be resolved, and recent experimental findings provide some reason for optimism. However, the problem of the origin of the RNA World is far from being solved, and it is fruitful to consider the alternative possibility that RNA was preceded by some other replicating, evolving molecule, just as DNA and proteins were preceded by RNA. PMID:20739415

Lifespan extension by cranberry supplementation partially requires SOD2 and is life stage independent.

PubMed

Sun, Yaning; Yolitz, Jason; Alberico, Thomas; Sun, Xiaoping; Zou, Sige

2014-02-01

Many nutraceuticals and pharmaceuticals have been shown to promote healthspan and lifespan. However, the mechanisms underlying the beneficial effects of prolongevity interventions and the time points at which interventions should be implemented to achieve beneficial effects are not well characterized. We have previously shown that a cranberry-containing nutraceutical can promote lifespan in worms and flies and delay age-related functional decline of pancreatic cells in rats. Here we investigated the mechanism underlying lifespan extension induced by cranberry and the effects of short-term or life stage-specific interventions with cranberry on lifespan in Drosophila. We found that lifespan extension induced by cranberry was associated with reduced phosphorylation of ERK, a component of oxidative stress response MAPK signaling, and slightly increased phosphorylation of AKT, a component of insulin-like signaling. Lifespan extension was also associated with a reduced level of 4-hydroxynonenal protein adducts, a biomarker of lipid oxidation. Moreover, lifespan extension induced by cranberry was partially suppressed by knockdown of SOD2, a major mitochondrial superoxide scavenger. Furthermore, cranberry supplementation was administered in three life stages of adult flies, health span (3-30 days), transition span (31-60 days) and senescence span (61 days to the end when all flies died). Cranberry supplementation during any of these life stages extended the remaining lifespan relative to the non-supplemented and life stage-matched controls. These findings suggest that cranberry supplementation is sufficient to promote longevity when implemented during any life stage, likely through reducing oxidative damage. Published by Elsevier Inc.

Life-Span Exposure to Low Doses of Aspartame Beginning during Prenatal Life Increases Cancer Effects in Rats

PubMed Central

Soffritti, Morando; Belpoggi, Fiorella; Tibaldi, Eva; Esposti, Davide Degli; Lauriola, Michelina

2007-01-01

Background In a previous study conducted at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation (CMCRC/ERF), we demonstrated for the first time that aspartame (APM) is a multipotent carcinogenic agent when various doses are administered with feed to Sprague-Dawley rats from 8 weeks of age throughout the life span. Objective The aim of this second study is to better quantify the carcinogenic risk of APM, beginning treatment during fetal life. Methods We studied groups of 70–95 male and female Sprague-Dawley rats administered APM (2,000, 400, or 0 ppm) with feed from the 12th day of fetal life until natural death. Results Our results show a) a significant dose-related increase of malignant tumor–bearing animals in males (p < 0.01), particularly in the group treated with 2,000 ppm APM (p < 0.01); b) a significant increase in incidence of lymphomas/leukemias in males treated with 2,000 ppm (p < 0.05) and a significant dose-related increase in incidence of lymphomas/leukemias in females (p < 0.01), particularly in the 2,000-ppm group (p < 0.01); and c) a significant dose-related increase in incidence of mammary cancer in females (p < 0.05), particularly in the 2,000-ppm group (p < 0.05). Conclusions The results of this carcinogenicity bioassay confirm and reinforce the first experimental demonstration of APM’s multipotential carcinogenicity at a dose level close to the acceptable daily intake for humans. Furthermore, the study demonstrates that when life-span exposure to APM begins during fetal life, its carcinogenic effects are increased. PMID:17805418

Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans

PubMed Central

Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley; Lee, Kristy; Robinson, Rosann; Campbell, Michael S.; Kiso, Wendy K.; Schmitt, Dennis L.; Waddell, Peter J; Bhaskara, Srividya; Jensen, Shane T.; Maley, Carlo C.; Schiffman, Joshua D.

2016-01-01

IMPORTANCE Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. OBJECTIVE To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). DESIGN, SETTING, AND PARTICIPANTS A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. EXPOSURES Ionizing radiation and doxorubicin. MAIN OUTCOMES AND MEASURES Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. RESULTS Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95%CI, 0%–5%]; African wild dog, 8%[95%CI, 0%–16%]; lion, 2%[95%CI, 0% –7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95%CI, 3.14%–6.49%), compared with humans, who have 11% to 25%cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95%CI, 1.93%–3.48%] vs human controls, 7.17%[95%CI, 5.91%–8.44%] vs elephants, 14.64%[95%CI, 10.91%–18.37%]; P < .001; doxorubicin exposure: human controls, 8.10% [95%CI, 6.55%–9.66%] vs elephants, 24.77%[95%CI, 23.0%–26.53%]; P < .001). CONCLUSIONS AND RELEVANCE Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression. PMID:26447779

Developmental change in proactive interference across the life span: evidence from two working memory tasks.

PubMed

Loosli, Sandra V; Rahm, Benjamin; Unterrainer, Josef M; Weiller, Cornelius; Kaller, Christoph P

2014-04-01

Working memory (WM) as the ability to temporarily maintain and manipulate various kinds of information is known to be affected by proactive interference (PI) from previously relevant contents, but studies on developmental changes in the susceptibility to PI are scarce. In the present study, we investigated life span development of item-specific PI. To this end, 92 individuals between the ages of 8 and 74 years completed a recent-probes task and an n-back task that both composed experimental manipulations of PI. Regarding global WM development, young adults had higher WM performance than children and older adults in both tasks. Significant PI × Age interactions revealed that susceptibility to PI changed over the life span in both tasks, whereas the developmental course of PI differed between the tasks: Children committed more PI-related errors than young adults in the recent-probes task but showed marginally less PI in the n-back task. Regarding reaction time costs, children did not differ from adults in the recent-probes task and were less affected than adults in the n-back. Older adults showed more PI-related errors than young adults in both tasks. Therefore, as expected, item-specific PI changed over the life span with the young adults being less susceptible to PI than children and older adults. The diverging developmental effects of PI across both tasks, especially in the children, are supposed to reflect different causes for the difficulties regarding resisting PI in children and older adults. These might concern differently developed underlying cognitive processes such as inhibition or recollection, or different responses to task demands across both tasks. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Photosynthetic thermotolerance of woody savanna species in China is correlated with leaf life span

PubMed Central

Zhang, Jiao-Lin; Poorter, L.; Hao, Guang-You; Cao, Kun-Fang

2012-01-01

Background and Aims Photosynthetic thermotolerance (PT) is important for plant survival in tropical and sub-tropical savannas. However, little is known about thermotolerance of tropical and sub-tropical wild plants and its association with leaf phenology and persistence. Longer-lived leaves of savanna plants may experience a higher risk of heat stress. Foliar Ca is related to cell integrity of leaves under stresses. In this study it is hypothesized that (1) species with leaf flushing in the hot-dry season have greater PT than those with leaf flushing in the rainy season; and (2) PT correlates positively with leaf life span, leaf mass per unit area (LMA) and foliar Ca concentration ([Ca]) across woody savanna species. Methods The temperature-dependent increase in minimum fluorescence was measured to assess PT, together with leaf dynamics, LMA and [Ca] for a total of 24 woody species differing in leaf flushing time in a valley-type savanna in south-west China. Key Results The PT of the woody savanna species with leaf flushing in the hot-dry season was greater than that of those with leaf flushing in the rainy season. Thermotolerance was positively associated with leaf life span and [Ca] for all species irrespective of the time of flushing. The associations of PT with leaf life span and [Ca] were evolutionarily correlated. Thermotolerance was, however, independent of LMA. Conclusions Chinese savanna woody species are adapted to hot-dry habitats. However, the current maximum leaf temperature during extreme heat stress (44·3 °C) is close to the critical temperature of photosystem II (45·2 °C); future global warming may increase the risk of heat damage to the photosynthetic apparatus of Chinese savanna species. PMID:22875810

Hour Glass Half-Full or Half-Empty? Future Time Perspective and Preoccupation with Negative Events Across the Life Span

PubMed Central

Strough, JoNell; de Bruin, Wändi Bruine; Parker, Andrew M.; Lemaster, Philip; Pichayayothin, Nipat; Delaney, Rebecca

2016-01-01

According to socioemotional selectivity theory, older adults' emotional well-being stems from having limited future time perspective that motivates them to maximize well-being in the “here and now.” Presumably, then, older adults' time horizons are associated with emotional competencies that boost positive affect and dampen negative affect, but little research has addressed this. Using a US national adult life-span sample (N= 3,933, 18-93 yrs), we found that a two-factor model of future time perspective (focus on future opportunities; focus on limited time) fit the data better than a one-factor model. Through middle age, people perceived the life-span hourglass as half full—they focused more on future opportunities than limited time. Around age 60, the balance changed to increasingly perceiving the life-span hourglass as half empty—they focused less on future opportunities and more on limited time. This pattern held even after accounting for perceived health, self-reported decision-making ability, and retirement status. At all ages, women's time horizons focused more on future opportunities compared to men's, and men's focused more on limited time. Focusing on future opportunities was associated with reporting less preoccupation with negative events, whereas focusing on limited time was associated with reporting more preoccupation. Older adults reported less preoccupation with negative events and this association was stronger after controlling for their perceptions of limited time and fewer future opportunities, suggesting that other pathways may explain older adults' reports of their ability to disengage from negative events. Insights gained and questions raised by measuring future time perspective as two dimensions are discussed. PMID:27267222

Late-onset temperature reduction can retard the aging process in aged fish via a combined action of an anti-oxidant system and the insulin/insulin-like growth factor 1 signaling pathway.

PubMed

Wang, Xia; Chang, Qingyun; Wang, Yu; Su, Feng; Zhang, Shicui

2014-12-01

Two different mechanisms are considered to be related to aging. Cumulative molecular damage caused by reactive oxygen species (ROS), the by-products of oxidative phosphorylation, is one of these mechanisms (ROS concept). Deregulated nutrient sensing by the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway is the second mechanism (IIS concept). Temperature reduction (TR) is known to modulate aging and prolong life span in a variety of organisms, but the mechanisms remain poorly defined. Here we first demonstrate that late-onset TR from 26 °C to 22 °C extends mean life span and maximum life span by approximately 5.2 and 3 weeks, respectively, in the annual fish Nothobranchius guentheri. We then show that TR is able to decrease the accumulation of the histological aging markers senescence-associated β-galactosidase (SA-β-Gal) in the epithelium and lipofuscin (LF) in the liver and to reduce protein oxidation and lipid peroxidation levels in the muscle. We also show that TR can enhance the activities of catalase, glutathione peroxidase, and superoxide dismutase, and stimulate the synthesis of SirT1 and FOXO3A/FOXO1A, both of which are the downstream regulators of the IIS pathway. Taken together, our findings suggest that late-onset TR, a simple non-intrusion intervention, can retard the aging process in aged fish, resulting in their life span extension, via a synergistic action of an anti-oxidant system and the IIS pathway. This also suggests that combined assessment of the ROS and IIS concepts will contribute to providing a more comprehensive view of the anti-aging process.

eRapa Restores A Normal Life Span in a FAP Mouse Model

PubMed Central

Hasty, Paul; Livi, Carolina B.; Dodds, Sherry G.; Jones, Diane; Strong, Randy; Javors, Martin; Fischer, Kathleen E.; Sloane, Lauren; Murthy, Kruthi; Hubbard, Gene; Sun, Lishi; Hurez, Vincent; Curiel, Tyler J.; Sharp, Zelton Dave

2014-01-01

Mutation of a single copy of the adenomatous polyposis coli (APC) gene results in familial adenomatous polyposis (FAP), which confers an extremely high risk for colon cancer. ApcMin/+ mice exhibit multiple intestinal neoplasia (MIN) that causes anemia and death from bleeding by 6 months. Mechanistic target of rapamycin complex 1 (mTORC1) inhibitors were shown to improve ApcMin/+ mouse survival when administered by oral gavage or added directly to the chow, but these mice still died from neoplasia well short of a natural life span. The National Institute of Aging Intervention Testing Program showed that enterically targeted rapamycin (eRapa) extended life span for wild type genetically heterogeneous mice in part by inhibiting age-associated cancer. We hypothesized that eRapa would be effective in preventing neoplasia and extend survival of ApcMin/+ mice. We show that eRapa improved survival for ApcMin/+ mice in a dose-dependent manner. Remarkably, and in contrast to previous reports, most of the ApcMin/+ mice fed 42 ppm eRapa lived beyond the median life span reported for wild type syngeneic mice. Furthermore, chronic eRapa did not cause detrimental immune effects in mouse models of cancer, infection or autoimmunity; thus, assuaging concerns that chronic rapamycin treatment suppresses immunity. Our studies suggest that a novel formulation (enteric targeting) of a well-known and widely used drug (rapamycin) can dramatically improve its efficacy in targeted settings. eRapa or other mTORC1 inhibitors could serve as effective cancer preventatives for people with FAP without suppressing the immune system, thus reducing the dependency on surgery as standard therapy. PMID:24282255

Hour glass half full or half empty? Future time perspective and preoccupation with negative events across the life span.

PubMed

Strough, JoNell; Bruine de Bruin, Wändi; Parker, Andrew M; Lemaster, Philip; Pichayayothin, Nipat; Delaney, Rebecca

2016-09-01

According to socioemotional selectivity theory, older adults' emotional well-being stems from having a limited future time perspective that motivates them to maximize well-being in the "here and now." Presumably, then, older adults' time horizons are associated with emotional competencies that boost positive affect and dampen negative affect, but little research has addressed this. Using a U.S. adult life-span sample (N = 3,933; 18-93 years), we found that a 2-factor model of future time perspective (future opportunities; limited time) fit the data better than a 1-factor model. Through middle age, people perceived the life-span hourglass as half full-they focused more on future opportunities than limited time. Around Age 60, the balance changed to increasingly perceiving the life-span hourglass as half empty-they focused less on future opportunities and more on limited time, even after accounting for perceived health, self-reported decision-making ability, and retirement status. At all ages, women's time horizons focused more on future opportunities compared with men's, and men's focused more on limited time. Focusing on future opportunities was associated with reporting less preoccupation with negative events, whereas focusing on limited time was associated with reporting more preoccupation. Older adults reported less preoccupation with negative events, and this association was stronger after controlling for their perceptions of limited time and fewer future opportunities, suggesting that other pathways may explain older adults' reports of their ability to disengage from negative events. Insights gained and questions raised by measuring future time perspective as 2 dimensions are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Cardiac risk assessment: when and who? [Retrospectroscope].

PubMed

Valentinuzzi, M E; Arini, P D; Laciar, E; Bonomini, M P; Correa, R O

2013-07-01

Think about the above lines taken from the Old Testament: At 130 years of age, Adam begat a son and at 800 he kept going, quitting this earthly life at 930. These numbers surpass by far the limits our current experience teaches us, however, perhaps a life span into the hundreds of years is ? What if, in the future, science were to do away with disease? What then would cause people to die: accidents, killings, wars? How old would old age be? Aging has always been a hot topic for research (with considerable quackery, too). For example, animals with a slow metabolism tend to live longer than those with a fast metabolism. Compare the average life span of a mouse with that of a turtle. Apparently, meditators are able to slow their metabolism down [1].

HIV-1 infection: the role of the gastrointestinal tract.

PubMed

Cavarelli, Mariangela; Scarlatti, Gabriella

2014-06-01

The intestinal mucosa has an important role as portal of entry during mother-to-child transmission of HIV-1 and during sexual transmission. Tissue morphology and integrity, as well as distribution of relevant cell types within the mucosa, spanning from the oropharynx to the rectum, can greatly influence viral infection, replication, presentation, and persistence. The relative contribution to transmission by cell-associated or cell-free virus is still not defined for the different routes of transmission. Although the main target cells for HIV-1 replication are the CD4+ T lymphocytes, which are rapidly depleted both in the periphery and in the mucosal tissues, dendritic cells, Langerhans' cells, and macrophages are players in each of these processes. The predominant cells involved may differ according to the tract of the gut and the route of transmission. The microenvironment of the intestinal mucosa, including mucus, antibodies, or chemo-cytokines, can as well influence infection and replication of the virus: their role is still under investigation. The understanding of these processes may help in developing efficient prevention strategies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Human growth and body weight dynamics: an integrative systems model.

PubMed

Rahmandad, Hazhir

2014-01-01

Quantifying human weight and height dynamics due to growth, aging, and energy balance can inform clinical practice and policy analysis. This paper presents the first mechanism-based model spanning full individual life and capturing changes in body weight, composition and height. Integrating previous empirical and modeling findings and validated against several additional empirical studies, the model replicates key trends in human growth including A) Changes in energy requirements from birth to old ages. B) Short and long-term dynamics of body weight and composition. C) Stunted growth with chronic malnutrition and potential for catch up growth. From obesity policy analysis to treating malnutrition and tracking growth trajectories, the model can address diverse policy questions. For example I find that even without further rise in obesity, the gap between healthy and actual Body Mass Indexes (BMIs) has embedded, for different population groups, a surplus of 14%-24% in energy intake which will be a source of significant inertia in obesity trends. In another analysis, energy deficit percentage needed to reduce BMI by one unit is found to be relatively constant across ages. Accompanying documented and freely available simulation model facilitates diverse applications customized to different sub-populations.

Emotional reactivity across the adult life span: the cognitive pragmatics make a difference.

PubMed

Kunzmann, Ute; Richter, David

2009-12-01

Previously, we found that during films about age-typical losses, older adults experienced greater sadness than young adults, whereas their physiological responses were just as large. In the present study, our goal was to replicate this finding and extend past work by examining the role of cognitive functioning in age differences in emotional reactivity. We measured the autonomic and subjective responses of 240 adults (age range=20 to 70) while they viewed films about age-typical losses from our previous work. Findings were fully supportive of our past work: The magnitude of subjective reactions to our films increased linearly over the adult years, whereas there were no age differences on the level of physiological reactivity. We also found that the subjective reactions of adults with high pragmatic intelligence were of moderate size independent of their own age or the age relevance of the emotion elicitor. In contrast, the subjective reactions of adults low on pragmatic intelligence were more variable. Together, this evidence suggests that research on age differences in emotional reactivity may benefit from a perspective that considers individual difference variables as well as contextual variations. PsycINFO Database Record Copyright (c) 2009 APA, all rights reserved

Selenium preserves keratinocyte stemness and delays senescence by maintaining epidermal adhesion

PubMed Central

Jobeili, Lara; Rousselle, Patricia; Béal, David; Blouin, Eric; Roussel, Anne-Marie; Damour, Odile; Rachidi, Walid

2017-01-01

Skin is constantly exposed to environmental factors such as pollutants, chemicals and ultra violet radiation (UV), which can induce premature skin aging and increase the risk of skin cancer. One strategy to reduce the effect of oxidative stress produced by environmental exposure is the application of antioxidant molecules. Among the endogenous antioxidants, selenoproteins play a key role in antioxidant defense and in maintaining a reduced cellular environment. Selenium, essential for the activity of selenoproteins, is a trace element that is not synthesized by organisms and must be supplied by diet or supplementation. The aim of this study is to evaluate the effect of Selenium supplementation on skin aging, especially on keratinocytes, the main cells of the epidermis. Our results demonstrate for the first time to our knowledge, the major role of Selenium on the replicative life span of keratinocytes and on aging skin. Selenium protects keratinocyte stem cells (KSCs) against senescence via preservation of their stemness phenotype through adhesion to the basement membrane. Additionally, Selenium supplementation maintains the homeostasis of skin during chronological aging in our senescent skin equivalent model. Controlled supplementation with Selenium could be a new strategy to protect skin against aging. PMID:29176034

Human Growth and Body Weight Dynamics: An Integrative Systems Model

PubMed Central

Rahmandad, Hazhir

2014-01-01

Quantifying human weight and height dynamics due to growth, aging, and energy balance can inform clinical practice and policy analysis. This paper presents the first mechanism-based model spanning full individual life and capturing changes in body weight, composition and height. Integrating previous empirical and modeling findings and validated against several additional empirical studies, the model replicates key trends in human growth including A) Changes in energy requirements from birth to old ages. B) Short and long-term dynamics of body weight and composition. C) Stunted growth with chronic malnutrition and potential for catch up growth. From obesity policy analysis to treating malnutrition and tracking growth trajectories, the model can address diverse policy questions. For example I find that even without further rise in obesity, the gap between healthy and actual Body Mass Indexes (BMIs) has embedded, for different population groups, a surplus of 14%–24% in energy intake which will be a source of significant inertia in obesity trends. In another analysis, energy deficit percentage needed to reduce BMI by one unit is found to be relatively constant across ages. Accompanying documented and freely available simulation model facilitates diverse applications customized to different sub-populations. PMID:25479101

Genome-Wide Motif Statistics are Shaped by DNA Binding Proteins over Evolutionary Time Scales

NASA Astrophysics Data System (ADS)

Qian, Long; Kussell, Edo

The composition of genomes with respect to short DNA motifs impacts the ability of DNA binding proteins to locate and bind their target sites. Since nonfunctional DNA binding can be detrimental to cellular functions and ultimately to organismal fitness, organisms could benefit from reducing the number of nonfunctional binding sites genome wide. Using in vitro measurements of binding affinities for a large collection of DNA binding proteins, in multiple species, we detect a significant global avoidance of weak binding sites in genomes. The underlying evolutionary process leaves a distinct genomic hallmark in that similar words have correlated frequencies, which we detect in all species across domains of life. We hypothesize that natural selection against weak binding sites contributes to this process, and using an evolutionary model we show that the strength of selection needed to maintain global word compositions is on the order of point mutation rates. Alternative contributions may come from interference of protein-DNA binding with replication and mutational repair processes, which operates with similar rates. We conclude that genome-wide word compositions have been molded by DNA binding proteins through tiny evolutionary steps over timescales spanning millions of generations.

Erythrocyte and blood antibacterial defense

PubMed Central

2014-01-01

It is an axiom that blood cellular immunity is provided by leukocytes. As to erythrocytes, it is generally accepted that their main function is respiration. Our research provides objective video and photo evidence regarding erythrocyte bactericidal function. Phase-contrast immersion vital microscopy of the blood of patients with bacteremia was performed, and the process of bacteria entrapping and killing by erythrocytes was shot by means of video camera. Video evidence demonstrates that human erythrocytes take active part in blood bactericidal action and can repeatedly engulf and kill bacteria of different species and size. Erythrocytes are extremely important integral part of human blood cellular immunity. Compared with phagocytic leukocytes, the erythrocytes: a) are more numerous; b) are able to entrap and kill microorganisms repeatedly without being injured; c) are more resistant to infection and better withstand the attacks of pathogens; d) have longer life span and are produced faster; e) are inauspicious media for proliferation of microbes and do not support replication of chlamidiae, mycoplasmas, rickettsiae, viruses, etc.; and f) are more effective and uncompromised bacterial killers. Blood cellular immunity theory and traditional view regarding the function of erythrocytes in human blood should be revised. PMID:24883200

Longevity of clonal plants: why it matters and how to measure it

PubMed Central

de Witte, Lucienne C.; Stöcklin, Jürg

2010-01-01

Background Species' life-history and population dynamics are strongly shaped by the longevity of individuals, but life span is one of the least accessible demographic traits, particularly in clonal plants. Continuous vegetative reproduction of genets enables persistence despite low or no sexual reproduction, affecting genet turnover rates and population stability. Therefore, the longevity of clonal plants is of considerable biological interest, but remains relatively poorly known. Scope Here, we critically review the present knowledge on the longevity of clonal plants and discuss its importance for population persistence. Direct life-span measurements such as growth-ring analysis in woody plants are relatively easy to take, although, for many clonal plants, these methods are not adequate due to the variable growth pattern of ramets and difficult genet identification. Recently, indirect methods have been introduced in which genet size and annual shoot increments are used to estimate genet age. These methods, often based on molecular techniques, allow the investigation of genet size and age structure of whole populations, a crucial issue for understanding their viability and persistence. However, indirect estimates of clonal longevity are impeded because the process of ageing in clonal plants is still poorly understood and because their size and age are not always well correlated. Alternative estimators for genet life span such as somatic mutations have recently been suggested. Conclusions Empirical knowledge on the longevity of clonal species has increased considerably in the last few years. Maximum age estimates are an indicator of population persistence, but are not sufficient to evaluate turnover rates and the ability of long-lived clonal plants to enhance community stability and ecosystem resilience. In order to understand the dynamics of populations it will be necessary to measure genet size and age structure, not only life spans of single individuals, and to use such data for modelling of genet dynamics. PMID:20880935

Stress responses, vitagenes and hormesis as critical determinants in aging and longevity: Mitochondria as a "chi".

PubMed

Cornelius, Carolin; Perrotta, Rosario; Graziano, Antonio; Calabrese, Edward J; Calabrese, Vittorio

2013-04-25

Understanding mechanisms of aging and determinants of life span will help to reduce age-related morbidity and facilitate healthy aging. Average lifespan has increased over the last centuries, as a consequence of medical and environmental factors, but maximal life span remains unchanged. Extension of maximal life span is currently possible in animal models with measures such as genetic manipulations and caloric restriction (CR). CR appears to prolong life by reducing reactive oxygen species (ROS)-mediated oxidative damage. But ROS formation, which is positively implicated in cellular stress response mechanisms, is a highly regulated process controlled by a complex network of intracellular signaling pathways. By sensing the intracellular nutrient and energy status, the functional state of mitochondria, and the concentration of ROS produced in mitochondria, the longevity network regulates life span across species by coordinating information flow along its convergent, divergent and multiply branched signaling pathways, including vitagenes which are genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose-response, challenges long-standing beliefs about the nature of the dose-response in a lowdose zone, having the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Here we focus on possible signaling mechanisms involved in the activation of vitagenes resulting in enhanced defense against energy and stress resistance homeostasis dysiruption with consequent impact on longevity processes.

Ageless and Timeless: Perspectives on Giftedness across the Life Span

ERIC Educational Resources Information Center

Fiedler, Ellen D.

2016-01-01

Annemarie Roeper's timeless perspectives were demonstrated throughout her long and productive life. Her prolific writings and speeches continue to influence our understanding of giftedness at all ages and stages of life, and the time I spent with her had a profound and meaningful effect on my work. Annemarie incorporated her inner view of…

"Play" across the Life Cycle: From Initiative to Integrity to Transcendence

ERIC Educational Resources Information Center

Jones, Elizabeth

2011-01-01

In this autobiographical journey through life-span developmental theory, the author reflects on her life as a player, embedding it in the context of Erik Erikson and Joan Erikson's stages of human development. The author builds on these basic ideas--theory, storytelling, play, and development--and defines them as simply as possible.

Preparation for Old Age in Different Life Domains: Dimensions and Age Differences

ERIC Educational Resources Information Center

Kornadt, Anna E.; Rothermund, Klaus

2014-01-01

We investigated preparation for age-related changes from a multidimensional, life span perspective and administered a newly developed questionnaire to a large sample aged 30-80 years. Preparing for age-related changes was organized by life domains, with domain-specific types of preparation addressing obstacles and opportunities in the respective…

Life stage dependent responses to desiccation risk in the annual killifish Nothobranchius wattersi.

PubMed

Grégoir, A F; Philippe, C; Pinceel, T; Reniers, J; Thoré, E S J; Vanschoenwinkel, B; Brendonck, L

2017-09-01

To assess whether the annual killifish Nothobranchius wattersi responds plastically to a desiccation risk and whether this response is life stage dependent, life-history traits such as maturation time, fecundity and life span were experimentally measured in N. wattersi that were subjected to a drop in water level either as juveniles, as adults or both as juveniles and adults. Fish that were exposed to simulated pool drying as juveniles did not show changes in reproductive output or life span. Adults reacted by doubling short term egg deposition at the cost of a shorter lifespan. Overall, these results suggest that annual fish species can use phenotypic plasticity to maximize their reproductive output when faced with early pond drying, but this response appears to be life-stage specific. In addition to frogs and aquatic insects, phenotypic plasticity induced by forthcoming drought is now also confirmed in annual fishes and could well be a common feature of the limited number of fish taxa that manage to survive in this extreme environment. © 2017 The Fisheries Society of the British Isles.

Cloning SU8 silicon masters using epoxy resins to increase feature replicability and production for cell culture devices.

PubMed

Kamande, J W; Wang, Y; Taylor, A M

2015-05-01

In recent years, there has been a dramatic increase in the use of poly(dimethylsiloxane) (PDMS) devices for cell-based studies. Commonly, the negative tone photoresist, SU8, is used to pattern features onto silicon wafers to create masters (SU8-Si) for PDMS replica molding. However, the complexity in the fabrication process, low feature reproducibility (master-to-master variability), silane toxicity, and short life span of these masters have been deterrents for using SU8-Si masters for the production of cell culture based PDMS microfluidic devices. While other techniques have demonstrated the ability to generate multiple devices from a single master, they often do not match the high feature resolution (∼0.1 μm) and low surface roughness that soft lithography masters offer. In this work, we developed a method to fabricate epoxy-based masters that allows for the replication of features with high fidelity directly from SU8-Si masters via their PDMS replicas. By this method, we show that we could obtain many epoxy based masters with equivalent features to a single SU8-Si master with a low feature variance of 1.54%. Favorable feature transfer resolutions were also obtained by using an appropriate Tg epoxy based system to ensure minimal shrinkage of features ranging in size from ∼100 μm to <10 μm in height. We further show that surface coating epoxy masters with Cr/Au lead to effective demolding and yield PDMS chambers that are suitable for long-term culturing of sensitive primary hippocampal neurons. Finally, we incorporated pillars within the Au-epoxy masters to eliminate the process of punching media reservoirs and thereby reducing substantial artefacts and wastage.

Cloning SU8 silicon masters using epoxy resins to increase feature replicability and production for cell culture devices

PubMed Central

Kamande, J. W.; Wang, Y.; Taylor, A. M.

2015-01-01

In recent years, there has been a dramatic increase in the use of poly(dimethylsiloxane) (PDMS) devices for cell-based studies. Commonly, the negative tone photoresist, SU8, is used to pattern features onto silicon wafers to create masters (SU8-Si) for PDMS replica molding. However, the complexity in the fabrication process, low feature reproducibility (master-to-master variability), silane toxicity, and short life span of these masters have been deterrents for using SU8-Si masters for the production of cell culture based PDMS microfluidic devices. While other techniques have demonstrated the ability to generate multiple devices from a single master, they often do not match the high feature resolution (∼0.1 μm) and low surface roughness that soft lithography masters offer. In this work, we developed a method to fabricate epoxy-based masters that allows for the replication of features with high fidelity directly from SU8-Si masters via their PDMS replicas. By this method, we show that we could obtain many epoxy based masters with equivalent features to a single SU8-Si master with a low feature variance of 1.54%. Favorable feature transfer resolutions were also obtained by using an appropriate Tg epoxy based system to ensure minimal shrinkage of features ranging in size from ∼100 μm to <10 μm in height. We further show that surface coating epoxy masters with Cr/Au lead to effective demolding and yield PDMS chambers that are suitable for long-term culturing of sensitive primary hippocampal neurons. Finally, we incorporated pillars within the Au-epoxy masters to eliminate the process of punching media reservoirs and thereby reducing substantial artefacts and wastage. PMID:26180572

Establishment of human induced pluripotent stem cell lines from normal fibroblast TIG-1.

PubMed

Kumazaki, Tsutomu; Kurata, Sayaka; Matsuo, Taira; Mitsui, Youji; Takahashi, Tomoko

2011-06-01

Normal human cells have a replicative life span and therefore senesce. Usually, normal human cell strains are differentiated cells and reach a terminally differentiated state after a number of cell divisions. At present, definitive differences are not known between replicative senescence and terminal differentiation. TIG-1 is a human fibroblast strain established from fetal lung and has been used extensively in studies of cellular senescence, and numerous data were accumulated at the molecular level. Recently, a method for generating induced pluripotent stem cells (iPSCs) was developed. Using the method, we introduced four reprogramming genes to TIG-1 fibroblasts and succeeded in isolating colonies that had embryonic stem cell (ESC)-like morphologies. They showed alkaline phosphatase activity and expressed ESC markers, as shown by immunostaining of OCT4, SOX2, SSEA4, and TRA-1-81 as well as reverse-transcription polymerase chain reaction (RT-PCR) for OCT4 and NANOG transcripts. Thus, we succeeded in establishing iPSC clones from TIG-1. The iPSC clones could differentiate to cells originated from all three germ-cell layers, as shown by RT-PCR, for messenger RNA (mRNA) expression of α-fetoprotein (endoderm), MSX1 (mesoderm) and microtubule-associated protein 2 (ectoderm), and by immunostaining for α-fetoprotein (endoderm), α-smooth muscle actin (mesoderm), and β-III-tubulin (ectoderm). The iPSCs formed teratoma containing the structures developed from all three germ-cell layers in severe combined immune-deficiency mice. Thus, by comparing the aging process of parental TIG-1 cells and the differentiation process of iPSC-derived fibrocytes to fibroblasts, we can reveal the exact differences in processes between senescence and terminal differentiation.

Effector-Triggered Self-Replication in Coupled Subsystems.

PubMed

Komáromy, Dávid; Tezcan, Meniz; Schaeffer, Gaël; Marić, Ivana; Otto, Sijbren

2017-11-13

In living systems processes like genome duplication and cell division are carefully synchronized through subsystem coupling. If we are to create life de novo, similar control over essential processes such as self-replication need to be developed. Here we report that coupling two dynamic combinatorial subsystems, featuring two separate building blocks, enables effector-mediated control over self-replication. The subsystem based on the first building block shows only self-replication, whereas that based on the second one is solely responsive toward a specific external effector molecule. Mixing the subsystems arrests replication until the effector molecule is added, resulting in the formation of a host-effector complex and the liberation of the building block that subsequently engages in self-replication. The onset, rate and extent of self-replication is controlled by the amount of effector present. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spatiotemporal coupling and decoupling of gene transcription with DNA replication origins during embryogenesis in C. elegans

PubMed Central

Pourkarimi, Ehsan; Bellush, James M; Whitehouse, Iestyn

2016-01-01

The primary task of developing embryos is genome replication, yet how DNA replication is integrated with the profound cellular changes that occur through development is largely unknown. Using an approach to map DNA replication at high resolution in C. elegans, we show that replication origins are marked with specific histone modifications that define gene enhancers. We demonstrate that the level of enhancer associated modifications scale with the efficiency at which the origin is utilized. By mapping replication origins at different developmental stages, we show that the positions and activity of origins is largely invariant through embryogenesis. Contrary to expectation, we find that replication origins are specified prior to the broad onset of zygotic transcription, yet when transcription initiates it does so in close proximity to the pre-defined replication origins. Transcription and DNA replication origins are correlated, but the association breaks down when embryonic cell division ceases. Collectively, our data indicate that replication origins are fundamental organizers and regulators of gene activity through embryonic development. DOI: http://dx.doi.org/10.7554/eLife.21728.001 PMID:28009254

Geno- and phenotypic characteristics of a transfected babesia bovis 6-Cys-E knockout clonal line

USDA-ARS?s Scientific Manuscript database

Babesia bovis is an intra-erythrocytic tick transmitted apicomplexan protozoan parasite. It has a complex life style including asexual replication in the mammalian host and sexual replication occurring in the midgut of host tick vector, typically, Rhipicephalus microplus. Previous evidence showed th...

Did template-directed nucleation precede molecular replication?

NASA Technical Reports Server (NTRS)

Orgel, Leslie E.

1986-01-01

It is proposed that mononucleotides incorporated into the surfaces of microcrystals of inorganic phosphates such as hydroxyapatite can act as templates to assemble complementary mononucleotides from solution, and that the phosphate groups of the assembled nucleotides can facilitate nucleation of a second hydroxyapatite crystal. This would provide a mechanism of replication that is subject to natural selection. The possible role of a replicating system of this kind in the origins of life on the earth is discussed.

Magnetohydrodynamic thermochemotherapy and MRI of mouse tumors

NASA Astrophysics Data System (ADS)

Brusentsov, Nikolay A.; Brusentsova, Tatiana N.; Filinova, Elena Yu.; Jurchenko, Nikolay Y.; Kupriyanov, Dmitry A.; Pirogov, Yuri A.; Dubina, Andry I.; Shumskikh, Maxim N.; Shumakov, Leonid I.; Anashkina, Ekaterina N.; Shevelev, Alexandr A.; Uchevatkin, Andry A.

2007-04-01

A dextran-ferrite magnetic fluid was successfully tested as magnetic resonance imaging (MRI) contrast agent. The same magnetic fluid was then combined with Melphalan, a chemotherapeutic drug, and used for magnetohydrodynamic thermochemotherapy of different tumors. The placement of the tumors in an AC magnetic field led to hyperthermia at 46 °C for 30 min. In combination with tumor slime aspiration, a 30% regression of ˜130 mm 3 non-metastatic P388 tumors in BDF 1 mice was reached, together with a life span increase of 290%. The same procedure associated with cyclophosphamide treatment of ˜500 mm 3 metastases tumor increased the animal's life span by 180%.

An Integrated Socio-Environmental Model of Health and Well-Being: a Conceptual Framework Exploring the Joint Contribution of Environmental and Social Exposures to Health and Disease Over the Life Span.

PubMed

Olvera Alvarez, Hector A; Appleton, Allison A; Fuller, Christina H; Belcourt, Annie; Kubzansky, Laura D

2018-06-01

Environmental and social determinants of health often co-occur, particularly among socially disadvantaged populations, yet because they are usually studied separately, their joint effects on health are likely underestimated. Building on converging bodies of literature, we delineate a conceptual framework to address these issues. Previous models provided a foundation for study in this area, and generated research pointing to additional important issues. These include a stronger focus on biobehavioral pathways, both positive and adverse health outcomes, and intergenerational effects. To accommodate the expanded set of issues, we put forward the Integrated Socio-Environmental Model of Health and Well-Being (ISEM), which examines how social and environmental factors combine and potentially interact, via multi-factorial pathways, to affect health and well-being over the life span. We then provide applied examples including the study of how food environments affect dietary behavior. The ISEM provides a comprehensive, theoretically informed framework to guide future research on the joint contribution of social and environmental factors to health and well-being across the life span.

Time scale matters: genetic analysis does not support adaptation-by-time as the mechanism for adaptive seasonal declines in kokanee reproductive life span

PubMed Central

Morbey, Yolanda E; Jensen, Evelyn L; Russello, Michael A

2014-01-01

Seasonal declines of fitness-related traits are often attributed to environmental effects or individual-level decisions about reproductive timing and effort, but genetic variation may also play a role. In populations of Pacific salmon (Oncorhynchus spp.), seasonal declines in reproductive life span have been attributed to adaptation-by-time, in which divergent selection for different traits occurs among reproductively isolated temporal components of a population. We evaluated this hypothesis in kokanee (freshwater obligate Oncorhynchus nerka) by testing for temporal genetic structure in neutral and circadian-linked loci. We detected no genetic differences in presumably neutral loci among kokanee with different arrival and maturation dates within a spawning season. Similarly, we detected no temporal genetic structure in OtsClock1b, Omy1009uw, or OmyFbxw11, candidate loci associated with circadian function. The genetic evidence from this study and others indicates a lack of support for adaptation-by-time as an important evolutionary mechanism underlying seasonal declines in reproductive life span and a need for greater consideration of other mechanisms such as time-dependent, adaptive adjustment of reproductive effort. PMID:25478160

Lifespan development of pro- and anti-saccades: multiple regression models for point estimates.

PubMed

Klein, Christoph; Foerster, Friedrich; Hartnegg, Klaus; Fischer, Burkhart

2005-12-07

The comparative study of anti- and pro-saccade task performance contributes to our functional understanding of the frontal lobes, their alterations in psychiatric or neurological populations, and their changes during the life span. In the present study, we apply regression analysis to model life span developmental effects on various pro- and anti-saccade task parameters, using data of a non-representative sample of 327 participants aged 9 to 88 years. Development up to the age of about 27 years was dominated by curvilinear rather than linear effects of age. Furthermore, the largest developmental differences were found for intra-subject variability measures and the anti-saccade task parameters. Ageing, by contrast, had the shape of a global linear decline of the investigated saccade functions, lacking the differential effects of age observed during development. While these results do support the assumption that frontal lobe functions can be distinguished from other functions by their strong and protracted development, they do not confirm the assumption of disproportionate deterioration of frontal lobe functions with ageing. We finally show that the regression models applied here to quantify life span developmental effects can also be used for individual predictions in applied research contexts or clinical practice.

A mitochondrial mutator plasmid that causes senescence under dietary restricted conditions

PubMed Central

Maas, Marc FPM; Hoekstra, Rolf F; Debets, Alfons JM

2007-01-01

Background Calorie or dietary restriction extends life span in a wide range of organisms including the filamentous fungus Podospora anserina. Under dietary restricted conditions, P. anserina isolates are several-fold longer lived. This is however not the case in isolates that carry one of the pAL2-1 homologous mitochondrial plasmids. Results We show that the pAL2-1 homologues act as 'insertional mutators' of the mitochondrial genome, which may explain their negative effect on life span extension. Sequencing revealed at least fourteen unique plasmid integration sites, of which twelve were located within the mitochondrial genome and two within copies of the plasmid itself. The plasmids were able to integrate in their entirety, via a non-homologous mode of recombination. Some of the integrated plasmid copies were truncated, which probably resulted from secondary, post-integrative, recombination processes. Integration sites were predominantly located within and surrounding the region containing the mitochondrial rDNA loci. Conclusion We propose a model for the mechanism of integration, based on innate modes of mtDNA recombination, and discuss its possible link with the plasmid's negative effect on dietary restriction mediated life span extension. PMID:17407571

Dissociable Changes of Frontal and Parietal Cortices in Inherent Functional Flexibility across the Human Life Span.

PubMed

Yin, Dazhi; Liu, Wenjing; Zeljic, Kristina; Wang, Zhiwei; Lv, Qian; Fan, Mingxia; Cheng, Wenhong; Wang, Zheng

2016-09-28

Extensive evidence suggests that frontoparietal regions can dynamically update their pattern of functional connectivity, supporting cognitive control and adaptive implementation of task demands. However, it is largely unknown whether this flexibly functional reconfiguration is intrinsic and occurs even in the absence of overt tasks. Based on recent advances in dynamics of resting-state functional resonance imaging (fMRI), we propose a probabilistic framework in which dynamic reconfiguration of intrinsic functional connectivity between each brain region and others can be represented as a probability distribution. A complexity measurement (i.e., entropy) was used to quantify functional flexibility, which characterizes heterogeneous connectivity between a particular region and others over time. Following this framework, we identified both functionally flexible and specialized regions over the human life span (112 healthy subjects from 13 to 76 years old). Across brainwide regions, we found regions showing high flexibility mainly in the higher-order association cortex, such as the lateral prefrontal cortex (LPFC), lateral parietal cortex, and lateral temporal lobules. In contrast, visual, auditory, and sensory areas exhibited low flexibility. Furthermore, we observed that flexibility of the right LPFC improved during maturation and reduced due to normal aging, with the opposite occurring for the left lateral parietal cortex. Our findings reveal dissociable changes of frontal and parietal cortices over the life span in terms of inherent functional flexibility. This study not only provides a new framework to quantify the spatiotemporal behavior of spontaneous brain activity, but also sheds light on the organizational principle behind changes in brain function across the human life span. Recent neuroscientific research has demonstrated that the human capability of adaptive task control is primarily the result of the flexible operation of frontal brain networks. However, it remains unclear whether this flexibly functional reconfiguration is intrinsic and occurs in the absence of an overt task. In this study, we propose a probabilistic framework to quantify the functional flexibility of each brain region using resting-state fMRI. We identify regions showing high flexibility mainly in the higher-order association cortex. In contrast, primary and unimodal visual and sensory areas show low flexibility. On the other hand, our findings reveal dissociable changes of frontal and parietal cortices in terms of inherent functional flexibility over the life span. Copyright © 2016 the authors 0270-6474/16/3610060-15$15.00/0.

"A general benevolence dimension that links neural, psychological, economic, and life-span data on altruistic tendencies": Correction to Hubbard et al. (2016).

PubMed

2016-10-01

Reports an error in "A general benevolence dimension that links neural, psychological, economic, and life-span data on altruistic tendencies" by Jason Hubbard, William T. Harbaugh, Sanjay Srivastava, David Degras and Ulrich Mayr ( Journal of Experimental Psychology: General , Advanced Online Publication, Aug 11, 2016, np). In the article, there was an error in the Task, Stimuli, and Procedures section. In the 1st sentence in the 6th paragraph, “Following the scanning phase, participants completed self-report questionnaires meant to reflected the Prosocial Disposition construct: the agreeableness scale from the Big F, which includes empathic concern and perspective-taking, and a scale of personality descriptive adjectives related to altruistic behavior (Wood, Nye, & Saucier, 2010).” should have read: “Following the scanning phase, participants completed self-report questionnaires that contained scales to reflect the Prosocial Disposition construct: the Big Five Inventory (BFI; John et al., 1991), from which we used the agreeableness scale to measure prosocial disposition; the Interpersonal Reactivity Index (IRI; Davis, 1980), from which we used the empathic concern and perspective-taking scales; and a scale of personality descriptive adjectives related to altruistic behavior (Wood, Nye, & Saucier, 2010).” (The following abstract of the original article appeared in record 2016-39037-001.) Individual and life span differences in charitable giving are an important economic force, yet the underlying motives are not well understood. In an adult, life span sample, we assessed manifestations of prosocial tendencies across 3 different measurement domains: (a) psychological self-report measures, (b) actual giving choices, and (c) fMRI-derived, neural indicators of “pure altruism.” The latter expressed individuals’ activity in neural valuation areas when charities received money compared to when oneself received money and thus reflected an altruistic concern for others. Results based both on structural equation modeling and unit-weighted aggregate scores revealed a strong higher-order General Benevolence dimension that accounted for variability across all measurement domains. The fact that the neural measures likely reflect pure altruistic tendencies indicates that General Benevolence is based on a genuine concern for others. Furthermore, General Benevolence exhibited a robust increase across the adult life span, potentially providing an explanation for why older adults typically contribute more to the public good than young adults. PsycINFO Database Record (c) 2016 APA, all rights reserved

Meaning and Purpose in Life across the Life Span: A Cross-Sectional Multivariate Analysis.

ERIC Educational Resources Information Center

Reker, Gary T.; And Others

This paper explores the developmental changes in meaning and purpose across the life course. Thirty males and females at the developmental stages of young adulthood (16-29 years), early middle-age (30-49 years), late middle-age (50-64 years), young-old (65-74 years) and old-old (75+ years) completed the Reker and Peacock (1981) Life Attitude…

The Study of Life Review. An Approach to the Investigation of Intellectual Development across the Life Span. Studien und Berichte 47.

ERIC Educational Resources Information Center

Staudinger, Ursula M.

A study looked for age differences in the quality of responses to the Life Review Task (LRT), studied the LRT itself as a tool for exploring wisdom and intellectual functioning in adulthood, and considered personality characteristics and life experience as alternative predictors of response quality. Sixty-three West German women of different ages…

Life Satisfaction Shows Terminal Decline in Old Age: Longitudinal Evidence from the German Socio-Economic Panel Study (SOEP)

ERIC Educational Resources Information Center

Gerstorf, Denis; Ram, Nilam; Estabrook, Ryne; Schupp, Jurgen; Wagner, Gert G.; Lindenberger, Ulman

2008-01-01

Longitudinal data spanning 22 years, obtained from deceased participants of the German Socio-Economic Panel Study (SOEP; N = 1,637; 70- to 100-year-olds), were used to examine if and how life satisfaction exhibits terminal decline at the end of life. Changes in life satisfaction were more strongly associated with distance to death than with…

The Inherent Asymmetry of DNA Replication.

PubMed

Snedeker, Jonathan; Wooten, Matthew; Chen, Xin

2017-10-06

Semiconservative DNA replication has provided an elegant solution to the fundamental problem of how life is able to proliferate in a way that allows cells, organisms, and populations to survive and replicate many times over. Somewhat lost, however, in our admiration for this mechanism is an appreciation for the asymmetries that occur in the process of DNA replication. As we discuss in this review, these asymmetries arise as a consequence of the structure of the DNA molecule and the enzymatic mechanism of DNA synthesis. Increasing evidence suggests that asymmetries in DNA replication are able to play a central role in the processes of adaptation and evolution by shaping the mutagenic landscape of cells. Additionally, in eukaryotes, recent work has demonstrated that the inherent asymmetries in DNA replication may play an important role in the process of chromatin replication. As chromatin plays an essential role in defining cell identity, asymmetries generated during the process of DNA replication may play critical roles in cell fate decisions related to patterning and development.

Antioxidant Capacity of “Mexican Arnica” Heterotheca inuloides Cass Natural Products and Some Derivatives: Their Anti-Inflammatory Evaluation and Effect on C. elegans Life Span

PubMed Central

Rodríguez-Chávez, José Luis; Nieto-Camacho, Antonio; Delgado-Lamas, Guillermo

2015-01-01

It has been suggested that the accumulation of biomolecular damage caused by reactive oxygen species (ROS) contributes to aging. The antioxidant activity is related to the ability of certain compounds to protect against the potentially harmful effect of processes or reactions involving ROS. This ability is associated with the termination of free radical propagation in biological systems. From Heterotheca inuloides various compounds which have shown to possess antioxidant capacity and scavenging ROS. The aim of this study was to determine the antioxidant capacity of additional natural components isolated from H. inuloides and some semisynthetic derivatives, their anti-inflammatory activity and the effect on Caenorhabditis elegans nematode life span. Compounds showed ability to inhibit various biological processes such as lipid peroxidation, scavenge nonbiological important oxidants such as 1O2, OH∙, H2O2, and HOCl and scavenge non biological stable free radicals (DPPH). Some cadinane type compounds showed possess antioxidant, ROS scavenging capacity, anti-inflammatory activity, and effect on the C. elegans life span. Flavonoid type compounds increased the life of the nematode and quercetin was identified as the compound with the greatest activity. The modification of chemical structure led to a change in the antioxidant capacity, the anti-inflammatory activity, and the survival of the worm. PMID:25821555

The mouse as a model organism in aging research: usefulness, pitfalls and possibilities.

PubMed

Vanhooren, Valerie; Libert, Claude

2013-01-01

The mouse has become the favorite mammalian model. Among the many reasons for this privileged position of mice is their genetic proximity to humans, the possibilities of genetically manipulating their genomes and the availability of many tools, mutants and inbred strains. Also in the field of aging, mice have become very robust and reliable research tools. Since laboratory mice have a life expectancy of only a few years, genetic approaches and other strategies for intervening in aging can be tested by examining their effects on life span and aging parameters during the relatively short period of, for example, a PhD project. Moreover, experiments on mice with an extended life span as well as on mice demonstrating signs of (segmental) premature aging, together with genetic mapping strategies, have provided novel insights into the fundamental processes that drive aging. Finally, the results of studies on caloric restriction and pharmacological anti-aging treatments in mice have a high degree of relevance to humans. In this paper, we review a number of recent genetic mapping studies that have yielded novel insights into the aging process. We discuss the value of the mouse as a model for testing interventions in aging, such as caloric restriction, and we critically discuss mouse strains with an extended or a shortened life span as models of aging. Copyright © 2012 Elsevier B.V. All rights reserved.

Communication and Distributed Control in Multi-Agent Systems

DTIC Science & Technology

2011-08-01

centre of mass of the simulated aircraft and moving with them, we can identify three class of rotations allowed to the MAVs: yaw, pitch, and roll. In...a customised version of the swinglet1 (see Figure 1), a 420g light 80cm wing-span mono/fixed-wing MAV produced by senseFlyTM2, generally used for...replicate its work in a faithful way. 2.3.2 Customised (Parker’s-based) implementation of Reynolds’ algo- rithm As aforementioned there are some degrees of

Sex and Race Disparities in Health: Cohort Variations in Life Course Patterns

ERIC Educational Resources Information Center

Yang, Yang; Lee, Linda C.

2009-01-01

This study assesses changes in sex and race disparities in health over the life course and across cohorts by conducting growth curve analyses of nationally representative longitudinal data that spans 15 years. It finds that changes in disparities in depressive symptoms, disability and self-assessments of health across the life course are…

Life Lived Well: A Description of Wellness across the Lifespan of a Senior Woman

ERIC Educational Resources Information Center

Jarnagin, Whitney L.; Woodside, Marianne

2012-01-01

The concept of wellness provides a positive view of life development that can support psychological support and counseling. There is little in the literature about wellness and seniors, especially women. This study describes one senior woman's wellness across the life span by addressing two research questions: (a) What are the experiences of one…

Cognitive changes and dementia risk after traumatic brain injury: implications for aging military personnel.

PubMed

Vincent, Andrea S; Roebuck-Spencer, Tresa M; Cernich, Alison

2014-06-01

Traumatic brain injury (TBI) is recognized as an important risk factor for the long-term cognitive health of military personnel, particularly in light of growing evidence that TBI increases risk for Alzheimer's disease and other dementias. In this article, we review the neurocognitive and neuropathologic changes after TBI with particular focus on the potential risk for cognitive decline across the life span in military service members. Implications for monitoring and surveillance of cognition in the aging military population are discussed. Additional studies are needed to clarify the factors that increase risk for later life cognitive decline, define the mechanistic link between these factors and dementia, and provide empirically supported interventions to mitigate the impact of TBI on cognition across the life span. Copyright © 2014 The Alzheimer's Association. All rights reserved.

Evolution of senescence in nature: physiological evolution in populations of garter snake with divergent life histories.

PubMed

Robert, Kylie A; Bronikowski, Anne M

2010-02-01

Evolutionary theories of aging are linked to life-history theory in that age-specific schedules of reproduction and survival determine the trajectory of age-specific mutation/selection balances across the life span and thus the rate of senescence. This is predicted to manifest at the organismal level in the evolution of energy allocation strategies of investing in somatic maintenance and robust stress responses in less hazardous environments in exchange for energy spent on growth and reproduction. Here we report experiments from long-studied populations of western terrestrial garter snakes (Thamnophis elegans) that reside in low and high extrinsic mortality environments, with evolved long and short life spans, respectively. Laboratory common-environment colonies of these two ecotypes were tested for a suite of physiological traits after control and stressed gestations. In offspring derived from control and corticosterone-treated dams, we measured resting metabolism; mitochondrial oxygen consumption, ATP and free radical production rates; and erythrocyte DNA damage and repair ability. We evaluated whether these aging biomarkers mirrored the evolution of life span and whether they were sensitive to stress. Neonates from the long-lived ecotype (1) were smaller, (2) consumed equal amounts of oxygen when corrected for body mass, (3) had DNA that damaged more readily but repaired more efficiently, and (4) had more efficient mitochondria and more efficient cellular antioxidant defenses than short-lived snakes. Many ecotype differences were enhanced in offspring derived from stress-treated dams, which supports the conclusion that nongenetic maternal effects may further impact the cellular stress defenses of offspring. Our findings reveal that physiological evolution underpins reptilian life histories and sheds light on the connectedness between stress response and aging pathways in wild-dwelling organisms.

Amyloid and the origin of life: self-replicating catalytic amyloids as prebiotic informational and protometabolic entities.

PubMed

Maury, Carl Peter J

2018-05-01

A crucial stage in the origin of life was the emergence of the first molecular entity that was able to replicate, transmit information, and evolve on the early Earth. The amyloid world hypothesis posits that in the pre-RNA era, information processing was based on catalytic amyloids. The self-assembly of short peptides into β-sheet amyloid conformers leads to extraordinary structural stability and novel multifunctionality that cannot be achieved by the corresponding nonaggregated peptides. The new functions include self-replication, catalytic activities, and information transfer. The environmentally sensitive template-assisted replication cycles generate a variety of amyloid polymorphs on which evolutive forces can act, and the fibrillar assemblies can serve as scaffolds for the amyloids themselves and for ribonucleotides proteins and lipids. The role of amyloid in the putative transition process from an amyloid world to an amyloid-RNA-protein world is not limited to scaffolding and protection: the interactions between amyloid, RNA, and protein are both complex and cooperative, and the amyloid assemblages can function as protometabolic entities catalyzing the formation of simple metabolite precursors. The emergence of a pristine amyloid-based in-put sensitive, chiroselective, and error correcting information-processing system, and the evolvement of mutualistic networks were, arguably, of essential importance in the dynamic processes that led to increased complexity, organization, compartmentalization, and, eventually, the origin of life.

Recent advances in the identification of the host factors involved in dengue virus replication.

PubMed

Wang, Yi; Zhang, Ping

2017-02-01

Dengue virus (DENV) belongs to the genus Flavivirus of the family Flaviviridae and it is primarily transmitted via Aedes aegypti and Aedes albopictus mosquitoes. The life cycle of DENV includes attachment, endocytosis, protein translation, RNA synthesis, assembly, egress, and maturation. Recent researches have indicated that a variety of host factors, including cellular proteins and microRNAs, positively or negatively regulate the DENV replication process. This review summarizes the latest findings (from 2014 to 2016) in the identification of the host factors involved in the DENV life cycle and Dengue infection.

The structure of late-life depressive symptoms across a 20-year span: a taxometric investigation.

PubMed

Holland, Jason M; Schutte, Kathleen K; Brennan, Penny L; Moos, Rudolf H

2010-03-01

Past studies of the underlying structure of depressive symptoms have yielded mixed results, with some studies supporting a continuous conceptualization and others supporting a categorical one. However, no study has examined this research question with an exclusively older adult sample, despite the potential uniqueness of late-life depressive symptoms. In the present study, the underlying structure of late-life depressive symptoms was examined among a sample of 1,289 individuals across 3 waves of data collection spanning 20 years. The authors employed a taxometric methodology using indicators of depression derived from the Research Diagnostic Criteria (R. L. Spitzer, J. Endicott, & E. Robins, 1978). Maximum eigenvalue analyses and inchworm consistency tests generally supported a categorical conceptualization and identified a group that was primarily characterized by thoughts about death and suicide. However, compared to a categorical depression variable, depressive symptoms treated continuously were generally better predictors of relevant criterion variables. These findings suggest that thoughts of death and suicide may characterize a specific type of late-life depression, yet a continuous conceptualization still typically maximizes the predictive utility of late-life depressive symptoms.