The evolution of postreproductive life span as an insurance against indeterminacy

Postreproductive life span remains a puzzle for evolutionary biologists. The explanation of increased inclusive fitness through parental care after reproduction that applies for humans is unrealistic for many species. We propose a new selective mechanism, independent of parental care, which relies on the hypothesis that postreproductive life span can evolve as an insurance against indeterminacy: longer life expectancy reduces the risk of dying by chance before the cessation of reproductive activity. We demonstrate numerically that the duration of evolved postreproductive life span is indeed expected to increase with variability in life span duration. An unprecedented assay of 11 strains of the collembola Folsomia candida shows the existence of (1) postreproductive life span in the absence of parental care; (2) genetic variability in mean postreproductive life span and postreproductive life span variability itself; (3) strong genetic correlation between latter traits. This new explanation brings along the novel idea that loose canalization of a trait (here, somatic life span) can itself act as a selective pressure on other traits.     

Variability in the longevity of Drosophila imagoes under chronic irradiation at low doses

The investigation of life span variability induced by a chronic influence of low doses gamma irradiation on the laboratory stocks of D. melanogaster, distinguishing by mobile genetic units, were carried out. Shown was the link of life span alterations in D. melanogaster with features of cytotype and genotype in tested stocks and with induced apoptotic cell death. The life span variation can be determined by a genomic destabilisation with an induction of mobile genetic elements in conditions of chronic gamma irradiation.     

Genetics of life span in mice

Thymic involution that occurs earlier in some individuals than others may be the result of complex interactions between genetic factors and the environment. Such interactions may produce defects of thymus-dependent immune regulation associated with susceptibility to developing autoimmune diseases, malignancy, and an increased number of infections associated with aging.The major histocompatibility complex may be important in determining profiles of cause of death and length of life in mice. Genetic influences on life span involve interactions between loci and allelic interactions during life which may change following viral infections or exposure to other environmental factors. We have used different experimental protocols to study the influence of H-2 on life span and found that interactions between genetic regions, are inconsistent, particularly when comparing mice infected or not infected with Sendai virus.Genes important for life span need to be studied against many genetic backgrounds and under differing environmental conditions because of the complexity of the genetics of life span. Several genetic models were used to demonstrate that the MHC is a marker of life span in backcross and intercross male mice of the H-2^d and H-2^b genotypes in B10 congenic mice. Females lived longer than males in backcross and intercross mice, while males lived longer than females in B10 congenics. H-2^d was at a disadvantage for life span in backcross mice of the dilute brown and brown males exposed to Sendai infection, but intercross mice not exposed to Sendai virus of the same genotype were not at a disadvantage. H-2^d mice were not disadvantaged when compared to H-2^b in B10 congenics that had not been exposed to Sendai virus infection but the reverse was true when they were exposed. Overall, all our studies suggest that genetic influences in life span may involve interactions between loci and many allelic interactions in growing animals or humans. These genetic influences on life span may vary after they are exposed to infections or other environmental conditions. This paper emphasizes the need to use several genetic models, especially animals that have been monitored for infections, to study the genetics of life span.     

Genes That Regulate Both Development and Longevity in Caenorhabditis Elegans

The nematode Caenorhabditis elegans responds to conditions of overcrowing 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 determination 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.     

Genotype-environment interaction for quantitative trait loci affecting life span in Drosophila melanogaster

The nature of genetic variation for Drosophila longevity in a population of recombinant inbred lines was investigated by estimating quantitative genetic parameters and mapping quantitative trait loci (QTL) for adult life span in five environments: standard culture conditions, high and low temperature, and heat-shock and starvation stress. There was highly significant genetic variation for life span within each sex and environment. In the analysis of variance of life span pooled over sexes and environments, however, the significant genetic variation appeared in the genotype x sex and genotype x environment interaction terms. The genetic correlation of longevity across the sexes and environments was not significantly different from zero in these lines. We estimated map positions and effects of QTL affecting life span by linkage to highly polymorphic roo transposable element markers, using a multiple-trait composite interval mapping procedure. A minimum of 17 QTL were detected; all were sex and/or environment-specific. Ten of the QTL had sexually antagonistic or antagonistic pleiotropic effects in different environments. These data provide support for the pleiotropy theory of senescence and the hypothesis that variation for longevity might be maintained by opposing selection pressures in males and females and variable environments. Further work is necessary to assess the generality of these results, using different strains, to determine heterozygous effects and to map the life span QTL to the level of genetic loci.     

Quantitative trait loci for life span in Drosophila melanogaster: interactions with genetic background and larval density

The genetic architecture of variation in adult life span was examined for a population of recombinant inbred lines, each of which had been crossed to both inbred parental strains from which the lines were derived, after emergence from both high and low larval density. QTL affecting life span were mapped within each sex and larval density treatment by linkage to highly polymorphic roo-transposable element markers, using a composite interval mapping method. We detected a total of six QTL affecting life span; the additive effects and degrees of dominance for all were highly sex- and larval environment-specific. There were significant epistatic interactions between five of the life span QTL, the effects of which also differed according to genetic background, sex, and larval density. Five additional QTL were identified that contributed to differences among lines in their sensitivity to variation in larval density. Further fine-scale mapping is necessary to determine whether candidate genes within the regions to which the QTL map are actually responsible for the observed variation in life span.     

Multivariate intralocus sexual conflict in seed beetles

Intralocus sexual conflict (IaSC) is pervasive because males and females experience differences in selection but share much of the same genome. Traits with integrated genetic architecture should be reservoirs of sexually antagonistic genetic variation for fitness, but explorations of multivariate IaSC are scarce. Previously, we showed that upward artificial selection on male life span decreased male fitness but increased female fitness compared with downward selection in the seed beetle Callosobruchus maculatus. Here, we use these selection lines to investigate sex‐specific evolution of four functionally integrated traits (metabolic rate, locomotor activity, body mass, and life span) that collectively define a sexually dimorphic life‐history syndrome in many species. Male‐limited selection for short life span led to correlated evolution in females toward a more male‐like multivariate phenotype. Conversely, males selected for long life span became more female‐like, implying that IaSC results from genetic integration of this suite of traits. However, while life span, metabolism, and body mass showed correlated evolution in the sexes, activity did not evolve in males but, surprisingly, did so in females. This led to sexual monomorphism in locomotor activity in short‐life lines associated with detrimental effects in females. Our results thus support the general tenet that widespread pleiotropy generates IaSC despite sex‐specific genetic architecture.     

A molecular mechanism of chronological aging in yeast

The molecular mechanisms that cause organismal aging are a topic of intense scrutiny and debate. Dietary restriction extends the life span of many organisms, including yeast, and efforts are underway to understand the biochemical and genetic pathways that regulate this life span extension in model organisms. Here we describe the mechanism by which dietary restriction extends yeast chronological life span, defined as the length of time stationary yeast cells remain viable in a quiescent state. We find that aging under standard culture conditions is the result of a cell-extrinsic component that is linked to the pH of the culture medium. We identify acetic acid as a cell-extrinsic mediator of cell death during chronological aging, and demonstrate that dietary restriction, growth in a non-fermentable carbon source, or transferring cells to water increases chronological life span by reducing or eliminating extracellular acetic acid. Other life span extending environmental and genetic interventions, such as growth in high osmolarity media, deletion of SCH9 or RAS2, increase cellular resistance to acetic acid. We conclude that acetic acid induced morality is the primary mechanism of chronological aging in yeast under standard conditions.     

Genetic nature of individual frailty: comparison of two approaches.

The traditional frailty models used in genetic analysis of bivariate survival data assume that individual frailty (and longevity) is influenced by thousands of genes, and that the contribution of each separate gene is small. This assumption, however, does not have a solid biological basis. It may just happen that one or a small number of genes makes a major contribution to determining the human life span. To answer the questions about the nature of the genetic influence on life span using survival data, models are needed that specify the influence of major genes on individual frailty and longevity. The goal of this paper is to test the nature of genetic influences on individual frailty and longevity using survival data on Danish twins. We use a new bivariate survival model with one major gene influencing life span to analyse survival data on MZ (monozygotic) and DZ (dizygotic) twins. The analysis shows that two radically different classes of model provide an equally good fit to the data. However, the asymptotic behaviour of some conditional statistics is different in models from different classes. Because of the limited sample size of bivariate survival data we cannot draw reliable conclusions about the nature of genetic effects on life span. Additional information about tails of bivariate distribution or risk factors may help to solve this problem.     

Life span variation in 13 Drosophila species: a comparative study on life span,environmental variables and stress resistance

Recently, heterogeneity of the environment has been suggested as an important player in the evolution of life span variation. Established ageing theories propose that life span variation is the result of coevolution with other traits, such as stress resistance. This study aimed to compare these alternative hypotheses by examining the relationship between four environmental variables and different types of stress resistance traits with life span in 13 Drosophila species originating from tropical, subtropical and temperate environments (ecotypes). Average life span was found to differ significantly both between species and sexes, but only male life span correlated with the environment and cold resistance. While controlling for phylogeny, the environmental variable precipitation seasonality and resistance against cold‐induced stress explained most variation in male life span. Furthermore, male life span varied between species in a manner represented by environmental variables linked to the different ecotypes, such that tropical species lived longer and were less cold resistant. The current results suggest that general mechanisms underlying stress resistance and life span are unlikely. In addition, our results point to the environment independently shaping variation in life span and cold resistance rather than genetic interactions.     

Genetic maternal effects on human life span through the inheritance of mitochondrial DNA.

Ageing consists of an accumulation of changes with time both at the molecular and cellular levels, accompanying an increased susceptibility to diseases and death. If maternally inherited mitochondrial genes are involved in defining the nature and timing of ageing, and if there are genetic differences in their susceptibility to damage, a maternal contribution could be found in the inheritance of life span. The present study explores the inheritance pattern of longevity and discovers a significant genetic maternal component in human life span.     

Vitamins and aging: pathways to NAD+ synthesis

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.     

hpr1Δ Affects Ribosomal DNA Recombination and Cell Life Span in Saccharomyces cerevisiae

Multiple genetic pathways have been shown to regulate life span and aging in the yeast Saccharomyces cerevisiae. Here we show that loss of a component of the RNA polymerase II complex, Hpr1p, results in a decreased life span. Although hpr1Delta mutants have an increased rate of recombination within the ribosomal DNA (rDNA) array, this is not accompanied by an increase in extrachromosomal rDNA circles (ERCs). Analyses of mutants that affect replication of the rDNA array and suppressors that reverse the phenotypes of the hpr1Delta mutant show that the reduced life span is associated with increased genomic instability but not with increased ERC formation. The hpr1Delta mutant acts in a pathway distinct from previously described mutants that reduce life span.     

Changes in genetic architecture during relaxation in Drosophila melanogaster selected on divergent virgin life span

Artificial selection experiments often confer important information on the genetic correlations constraining the evolution of life history. After artificial selection has ceased however, selection pressures in the culture environment can change the correlation matrix again. Here, we reinvestigate direct and correlated responses in a set of lines of Drosophila melanogaster that were selected on virgin life span and for which selection has been relaxed for 10 years. The decrease in progeny production in long-lived lines, a strong indication of antagonistic pleiotropy, had disappeared during relaxation. This was associated with a higher cost of reproduction to long-lived flies in mated, but not in virgin life span. These data strongly suggest that genetic mechanisms of mated and virgin life span determination are partly independent. Furthermore, data on body weight, developmental time and viability indicated deleterious effects of longevity selection in either direction, giving rise to a nonlinear relationship with life span for these characters. In order to reclaim original patterns, we founded a new set of derived lines by resuming selection in mixed replicate lines of the original set. Although selection was successful, most patterns in correlated characters remained, showing that these new patterns are resistant to new episodes of selection.     

Selection on learning performance results in the correlated evolution of sexual dimorphism in life history

The evolution of learning can be constrained by trade‐offs. As male and female life histories often diverge, the relationship between learning and fitness may differ between the sexes. However, because sexes share much of their genome, intersexual genetic correlations can prevent males and females from reaching their sex‐specific optima resulting in intralocus sexual conflict (IaSC). To investigate if IaSC constraints sex‐specific evolution of learning, we selected Caenorhabditis remanei nematode females for increased or decreased olfactory learning performance and measured learning, life span (in mated and virgin worms), reproduction, and locomotory activity in both sexes. Males from downward‐selected female lines had higher locomotory activity and longer virgin life span but sired fewer progeny than males from upward‐selected female lines. In contrast, we found no effect of selection on female reproduction and downward‐selected females showed higher locomotory activity but lived shorter as virgins than upward‐selected females. Strikingly, selection on learning performance led to the reversal of sexual dimorphism in virgin life span. We thus show sex‐specific trade‐offs between learning, reproduction, and life span. Our results support the hypothesis that selection on learning performance can shape the evolution of sexually dimorphic life histories via sex‐specific genetic correlations.     

FLP Recombinase-Mediated Induction of Cu/Zn-Superoxide Dismutase Transgene Expression Can Extend the Life Span of Adult Drosophila melanogaster Flies

Yeast FLP recombinase was used in a binary transgenic system (“FLP-OUT”) to allow induced overexpression of catalase and/or Cu/Zn-superoxide dismutase (Cu/ZnSOD) in adult Drosophila melanogaster. Expression of FLP recombinase was driven by the heat-inducible hsp70 promoter. Once expressed, FLP catalyzed the rearrangement and activation of a target construct in which expression of catalase or Cu/ZnSOD cDNAs was driven by the constitutive actin5C promoter. In this way a brief heat pulse (120 or 180 min, total) of young adult flies activated transgene expression for the rest of the life span. FLP-OUT allows the effects of induced transgene expression to be analyzed in control (no heat pulse) and experimental (heat pulse) populations with identical genetic backgrounds. Under the conditions used, the heat pulse itself always had neutral or slightly negative effects on the life span. Catalase overexpression significantly increased resistance to hydrogen peroxide but had neutral or slightly negative effects on the mean life span. Cu/ZnSOD overexpression extended the mean life span up to 48%. Simultaneous overexpression of catalase with Cu/ZnSOD had no added benefit, presumably due to a preexisting excess of catalase. The data suggest that oxidative damage is one rate-limiting factor for the life span of adult Drosophila. Finally, experimental manipulation of the genetic background demonstrated that the life span is affected by epistatic interactions between the transgene and allele(s) at other loci.