Mortality rate acceleration and post-reproductive lifespan in matrilineal whale species

The strength of selection to increase the span of a life stage is dependent upon individuals at that stage being able to contribute towards individual fitness and the probability of their surviving to that stage. Complete reproductive cessation and a long post-reproductive female lifespan as found in humans are also found in killer whale (Orcinus orca) and short-finned pilot whale (Globicephala macrorhynchus), but not in the long-finned pilot whale (Globicephala melaena). Each species forms kin-based, stable matrilineal groups and exhibits kin-directed behaviours that could increase inclusive fitness. Here, the initial mortality rate and mortality rate-doubling time of females of these three closely related whale species are compared. The initial mortality rate shows little variation among pilot whale species; however mortality rate accelerates almost twice as fast in the long-finned pilot whale as it does in killer whale and short-finned pilot whale. Selection for a long post-reproductive female lifespan in matrilineal whales may therefore be determined by the proportion of females surviving past the point of reproductive cessation.     

Cellular lifespan and senescence: a complex balance between multiple cellular pathways

The study of cellular senescence and proliferative lifespan is becoming increasingly important because of the promises of autologous cell therapy, the need for model systems for tissue disease and the implication of senescent cell phenotypes in organismal disease states such as sarcopenia, diabetes and various cancers, among others. Here, we explain the concepts of proliferative cellular lifespan and cellular senescence, and we present factors that have been shown to mediate cellular lifespan positively or negatively. We review much recent literature and present potential molecular mechanisms by which lifespan mediation occurs, drawing from the fields of telomere biology, metabolism, NAD⁺ and sirtuin biology, growth factor signaling and oxygen and antioxidants. We conclude that cellular lifespan and senescence are complex concepts that are governed by multiple independent and interdependent pathways, and that greater understanding of these pathways, their interactions and their convergence upon specific cellular phenotypes may lead to viable therapies for tissue regeneration and treatment of age‐related pathologies, which are caused by or exacerbated by senescent cells in vivo.     

The interaction between reproductive lifespan and protandry in seasonal breeders

The timing and duration of reproductive activities are highly variable both at the individual and population level. Understanding how this variation evolved by natural selection is fundamental to understanding many important aspects of an organism's life history, ecology and behaviour. Here, we combine game theoretic principles governing reproductive timing and the evolutionary theory of senescence to study the interaction between protandry (the earlier arrival or emergence of males to breeding areas than females) and senescence in seasonal breeders. Our general model applies to males who are seeking to mate as frequently as possible over a relatively short period, and so is relevant to many organisms including annual insects and semelparous vertebrates. The model predicts that protandry and maximum reproductive lifespans should increase in environments characterized by high survival and by a low competitive cost of maintaining the somatic machinery necessary for survival. In relatively short seasons under these same conditions, seasonal declines in the reproductive lifespans of males of equivalent quality will be evolutionarily stable. However, over a broad range of potential values for daily survival and maintenance cost, reproductive lifespan is expected to be relatively short and constant throughout a large fraction of the season. We applied the model to sockeye (or kokanee) salmon Oncorhynchus nerka and show that pronounced seasonal declines in reproductive lifespan, a distinctive feature of semelparous Oncorhynchus spp., is likely part of a male mating strategy to maximize mating opportunities.     

Patterns of philopatry and longevity contribute to the evolution of post-reproductive lifespan in mammals

While menopause has long been known as a characteristic trait of human reproduction, evidence for post-reproductive lifespan (PRLS) has recently been found in other mammals. Adaptive and non-adaptive hypotheses have been proposed to explain the evolution of PRLS, but formal tests of these are rare. We use a phylogenetic approach to evaluate hypotheses for the evolution of PRLS among mammals. In contrast to theoretical models predicting that PRLS may be promoted by male philopatry (which increases relatedness between a female and her group in old age), we find little evidence that male philopatry led to the evolution of a post-reproductive period. However, the proportion of life spent post-reproductive was related to lifespan and patterns of philopatry, suggesting that the duration of PRLS may be impacted by both non-adaptive and adaptive processes. Finally, the proportion of females experiencing PRLS was higher in species with male philopaty and larger groups, in accordance with adaptive models of PRLS. We suggest that the origin of PRLS primarily follows the non-adaptive ‘mismatch’ scenario, but that patterns of philopatry may subsequently confer adaptive benefits of late-life helping.     

Social stress shortens lifespan in mice

Stress and low socioeconomic status in humans confer increased vulnerability to morbidity and mortality. However, this association is not mechanistically understood nor has its causation been explored in animal models thus far. Recently, cellular senescence has been suggested as a potential mechanism linking lifelong stress to age‐related diseases and shorter life expectancy in humans. Here, we established a causal role for lifelong social stress on shortening lifespan and increasing the risk of cardiovascular disease in mice. Specifically, we developed a lifelong chronic psychosocial stress model in which male mouse aggressive behavior is used to study the impact of negative social confrontations on healthspan and lifespan. C57BL/6J mice identified through unbiased cluster analysis for receiving high while exhibiting low aggression, or identified as subordinate based on an ethologic criterion, had lower median and maximal lifespan, and developed earlier onset of several organ pathologies in the presence of a cellular senescence signature. Critically, subordinate mice developed spontaneous early‐stage atherosclerotic lesions of the aortic sinuses characterized by significant immune cells infiltration and sporadic rupture and calcification, none of which was found in dominant subjects. In conclusion, we present here the first rodent model to study and mechanistically dissect the impact of chronic stress on lifespan and disease of aging. These data highlight a conserved role for social stress and low social status on shortening lifespan and increasing the risk of cardiovascular disease in mammals and identify a potential mechanistic link for this complex phenomenon.     

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

Large, long-lived species experience more lifetime cell divisions and hence a greater risk of spontaneous tumor formation than smaller, short-lived species. Large, long-lived species are thus expected to evolve more elaborate tumor suppressor systems. In previous work, we showed that telomerase activity coevolves with body mass, but not lifespan, in rodents: telomerase activity is repressed in the somatic tissues of large rodent species but remains active in small ones. Without telomerase activity, the telomeres of replicating cells become progressively shorter until, at some critical length, cells stop dividing. Our findings therefore suggested that repression of telomerase activity mitigates the increased risk of cancer in larger-bodied species but not necessarily longer-lived ones. These findings imply that other tumor suppressor mechanisms must mitigate increased cancer risk in long-lived species. Here, we examined the proliferation of fibroblasts from 15 rodent species with diverse body sizes and lifespans. We show that, consistent with repressed telomerase activity, fibroblasts from large rodents undergo replicative senescence accompanied by telomere shortening and overexpression of p16(Ink4a) and p21(Cip1/Waf1) cycline-dependent kinase inhibitors. Interestingly, small rodents with different lifespans show a striking difference: cells from small shorter-lived species display continuous rapid proliferation, whereas cells from small long-lived species display continuous slow proliferation. We hypothesize that cells of small long-lived rodents, lacking replicative senescence, have evolved alternative tumor-suppressor mechanisms that prevent inappropriate cell division in vivo and slow cell growth in vitro. Thus, large-bodied species and small but long-lived species have evolved distinct tumor suppressor mechanisms.     

Menopause in Free-Ranging Rhesus Macaques: Estimated Incidence, Relation to Body Condition, and Adaptive Significance

We examined the question of whether the occurrence of menopause in rhesus macaque (Macaca mulatta) females approximates that found in women from a life history standpoint. We used data from two provisioned free-ranging populations of rhesus macaques to estimate the probability that a juvenile female not only will survive to the potentially postmenopausal age of 25 years but also will cease to experience menstrual cycles between 25 and 27 years. We used the same data to assess whether an age-related deterioration in body condition can predict whether females 25 years old will be acyclic. Our analyses indicate that, within our study populations, (1) 1 in every 10 juvenile females can be expected eventually to undergo the climacteric, and (2) being in poor condition is strongly associated with being acyclic in old age. Current theory regarding the evolution of senescence in species that do not reproduce by binary fission posits that aging is a consequence of the force of natural selection declining with age. Inasmuch as the proportion of female rhesus macaque juveniles that ultimately experience menopause is small, and inasmuch as reproductive senescence does not appear to outpace organismal aging in general (as indexed by an age-related decline in body condition), we conclude that the occurrence of menopause in rhesus females is parsimoniously explained by the general evolutionary theory of aging and that the invocation of a special adaptive explanation, such as the grandmother hypothesis or a variant thereof, is unnecessary.     

Sexual dimorphism in the human post-reproductive life-span: Possible causes

The fact that human females exhibit a post-reproductive life-span (menopause) and males do not is considered in evolutionary perspective. Two possible non-adaptive (incidental) explanations are discussed and rejected on available evidence. This sex difference is then considered as a possible adaptive response to differential parental investment tendencies of the two sexes. This hypothesis is evaluated in the context of sexual selection theory and the pattern of other observed sex differences in Homo sapiens. Finally, an attempt is made to explain the emergence of contemporary human investment patterns in terms of the changing patterns of parental certainty brought about by the Neolithic revolution. Cross-cultural data on investment patterns by subsistence type are used to test this hypothesis.     

Postreproductive lifespans are rare in mammals

A species has a post‐reproductive stage if, like humans, a female entering the adult population can expect to live a substantial proportion of their life after their last reproductive event. However, it is conceptually and statistically challenging to distinguish these true post‐reproductive stages from the usual processes of senescence, which can result in females occasionally surviving past their last reproductive event. Hence, despite considerable interest, the taxonomic prevalence of post‐reproductive stages remains unclear and debated. In this study we use life tables constructed from published data on wild populations of mammals, and statistical measures of post‐reproductive lifespans, to distinguish true post‐reproductive stages from artefacts of senescence and demography in 52 species. We find post‐reproductive stages are rare in mammals and are limited to humans and a few species of toothed whales. By resolving this long‐standing debate, we hope to provide clarity for researchers in the field of evolutionary biology and a solid foundation for further studies investigating the evolution and adaptive significance of this unusual life history trait.     

Reproductive senescence and terminal investment in female Barbary macaques (Macaca sylvanus) at Salem

The reproductive history of 207 female Barbary macaques, living in a large outdoor enclosure in Southwest Germany, was studied during an 11-year period. The results yielded a significant relationship between female age and fecundity, with fertility rates lower than expected among young and old females. Analysis of the reproductive history of individual females revealed a significant decline in fertility from prime age (7–12 years) to mid age (13–19 years), and from mid age to old age (20–25 years). The proportion of long interbirth intervals increased steadily among aging females. Infant survival was not significantly related to maternal age, but offspring of old females showed the highest survivorship. Behavioral observations revealed that old mothers weaned their offspring significantly later than younger mothers, suggesting that prolongation of interbirth intervals is due not only to deteriorating physical condition but also to increased maternal investment, as life history theory predicts. Reproduction ceased during the middle of the third decade of life. Final cessation of estrous cycling invariably occurred 3 or 4 years after the birth of the last offspring, but a postreproductive life span of 5 years appears to be common in this population. Available data suggest that reproductive senescence and menopause are more common among nonhuman primates than widely believed and that both traits are part of an adaptive life history strategy.     

Female reproductive competition within families in rural Gambia

Many studies show that the extended human family can be helpful in raising offspring, with maternal grandmothers, in particular, improving offspring survival. However, less attention has been given to competition between female kin and co-residents. It has been argued that reproductive conflict between generations explains the evolution of menopause in cooperatively breeding species where females disperse, and that older females are related to the offspring of younger females through their sons, whereas younger, incoming females are unrelated to older females. This means the pattern of help will be asymmetric, so older females lose in reproductive conflict and become 'sterile helpers'. Here, we seek evidence for female reproductive competition using longitudinal demographic data from a rural Gambian population, and examine when women are helping or harming each other's reproductive success. We find that older women benefit and younger women suffer costs of reproductive competition with women in their compound. But the opposite is found for mothers and daughters; if mother and daughter's reproductive spans overlap, the older woman reduces her reproduction if the younger woman (daughter) reproduces, whereas daughters' fertility is unaffected by their mothers' reproduction. Married daughters are not generally co-resident with their mothers, so we find not only competition effects with co-resident females, but also with daughters who have dispersed. Dispersal varies across human societies, but our results suggest reproductive conflict could be influencing reproductive scheduling whatever the dispersal pattern. A cultural norm of late male marriage reduces paternal grandmother/daughter-in-law reproductive overlap almost to zero in this population. We argue that cultural norms surrounding residence and marriage are themselves cultural adaptations to reduce reproductive conflict between generations in human families.     

Is There Adaptive Value to Reproductive Termination in Japanese Macaques? A Test of Maternal Investment Hypotheses

Evolutionary biologists often argue that menopause evolved in the human female as the result of selection for a postreproductive phase of life, during which increased maternal investment in existing progeny could lead to enhanced survivorship of descendents. Adaptive theories relating menopause to enhanced maternal investment are known as the mother (first-generation) and grandmother (second-generation-offspring) hypotheses. Although menopause—universal midlife termination of reproduction—has not been documented in primates other than humans, some researchers have argued that postreproductive alloprimates also have a positive impact on the survivorship of first and second generation progeny. We tested the maternal investment hypotheses in Japanese macaques by comparing the survivorship of offspring, final infants, and great-offspring of females that terminated reproduction before death with females that continued to reproduce until death. SURVIVAL analyses revealed no significant difference in the survivorship of descendents of postreproductive and reproductive females, though final infants of postreproductive females were 13% more likely to survive than final infants of females that reproduced until death were. We also explored possible differences between these two groups of females, other than survivorship of progeny. We found no difference in dominance rank, matrilineal affiliation, body weight, infant sex ratio, age at first birth, fecundity rate or lifetime reproductive success. However, postreproductive females are significantly longer-lived than reproductive females and as a result experienced more years of reproduction and produced more infants in total. Apart from final infants, offspring survival is marginally lower in postreproductive females. Since offspring survival is not significantly enhanced in postreproductive females, the greater number of infants produced did not translate into greater lifetime reproductive success. Our findings fail to support the maternal investment hypotheses and instead suggest that reproductive termination in this population of Japanese macaques is most closely associated with enhanced longevity and its repercussions.     

Heuristic optimization of the general life history problem: A novel approach

Summary The general life history problem concerns the optimal allocation of resources to growth, survival and reproduction. We analysed this problem for a perennial model organism that decides once each year to switch from growth to reproduction. As a fitness measure we used the Malthusian parameterr, which we calculated from the Euler-Lotka equation. Trade-offs were incorporated by assuming that fecundity is size dependent, so that increased fecundity could only be gained by devoting more time to growth and less time to reproduction. To calculate numerically the optimalr for different growth dynamics and mortality regimes, we used a simplified version of the simulated annealing method. The major differences among optimal life histories resulted from different accumulation patterns of intrinsic mortalities resulting from reproductive costs. If these mortalities were accumulated throughout life, i.e. if they were senescent, a bangbang strategy was optimal, in which there was a single switch from growth to reproduction: after the age at maturity all resources were allocated to reproduction. If reproductive costs did not carry over from year to year, i.e. if they were not senescent, the optimal resource allocation resulted in a graded switch strategy and growth became indeterminate. Our numerical approach brings two major advantages for solving optimization problems in life history theory. First, its implementation is very simple, even for complex models that are analytically intractable. Such intractability emerged in our model when we introduced reproductive costs representing an intrinsic mortality. Second, it is not a backward algorithm. This means that lifespan does not have to be fixed at the begining of the computation. Instead, lifespan itself is a trait that can evolve. We suggest that heuristic algorithms are good tools for solving complex optimality problems in life history theory, in particular questions concerning the evolution of lifespan and senescence.     

Mapping of quantitative trait loci controlling lifespan in the short-lived fish Nothobranchius furzeri--a new vertebrate model for age research

The African annual fish Nothobranchius furzeri emerged as a new model for age research over recent years. Nothobranchius furzeri show an exceptionally short lifespan, age-dependent cognitive/behavioral decline, expression of age-related biomarkers, and susceptibility to lifespan manipulation. In addition, laboratory strains differ largely in lifespan. Here, we set out to study the genetics of lifespan determination. We crossed a short- to a long-lived strain, recorded lifespan, and established polymorphic markers. On the basis of genotypes of 411 marker loci in 404 F(2) progeny, we built a genetic map comprising 355 markers at an average spacing of 5.5 cM, 22 linkage groups (LGs) and 1965 cM. By combining marker data with lifespan values, we identified one genome-wide highly significant quantitative trait locus (QTL) on LG 9 (P < 0.01), which explained 11.3% of the F(2) lifespan variance, and three suggestive QTLs on LG 11, 14, and 17. We characterized the highly significant QTL by synteny analysis, because a genome sequence of N. furzeri was not available. We located the syntenic region on medaka chromosome 5, identified candidate genes, and performed fine mapping, resulting in a c. 40% reduction of the initial 95% confidence interval. We show both that lifespan determination in N. furzeri is polygenic, and that candidate gene detection is easily feasible by cross-species analysis. Our work provides first results on the way to identify loci controlling lifespan in N. furzeri and illustrates the potential of this vertebrate species as a genetic model for age research.     

Perceived social isolation,evolutionary fitness and health outcomes: a lifespan approach

Sociality permeates each of the fundamental motives of human existence and plays a critical role in evolutionary fitness across the lifespan. Evidence for this thesis draws from research linking deficits in social relationship—as indexed by perceived social isolation (i.e. loneliness)—with adverse health and fitness consequences at each developmental stage of life. Outcomes include depression, poor sleep quality, impaired executive function, accelerated cognitive decline, unfavourable cardiovascular function, impaired immunity, altered hypothalamic pituitary–adrenocortical activity, a pro-inflammatory gene expression profile and earlier mortality. Gaps in this research are summarized with suggestions for future research. In addition, we argue that a better understanding of naturally occurring variation in loneliness, and its physiological and psychological underpinnings, in non-human species may be a valuable direction to better understand the persistence of a ‘lonely’ phenotype in social species, and its consequences for health and fitness.     

NATURAL GENETIC VARIATION OF LIFE SPAN,REPRODUCTION, AND JUVENILE GROWTH IN DAPHNIA

The evolutionary theory of senescence predicts that high extrinsic mortality in natural populations should select for accelerated reproductive investment and shortened life span. Here, we test the theory with natural populations of the Daphnia pulex-pulicaria species complex, a group of freshwater zooplankton that spans an environmental gradient of habitat permanence. We document substantial genetic variation in demographic life-history traits among parent and hybrid populations of this complex. Populations from temporary ponds have shorter life spans, earlier and faster increases of intrinsic mortality risk, and earlier and steeper declines in fecundity than populations from permanent lakes. We also examine the age-specific contribution to fitness, measured by reproductive value, and to expected lifetime reproduction; these traits decline faster in populations from temporary ponds. Despite having more rapid senescence, pond Daphnia exhibit faster juvenile growth and higher early fitness, measured as population growth rate (r). Among populations within this species complex we observed negative genetic correlations between r and indices of life-history timing, suggesting trade-offs between early- and late-life performance. Our results cannot be explained by a trade-off between survival and fecundity or by nonevolutionary theories of senescence. Instead, our data are consistent with the evolutionary theory of senescence because the genetic variation in life histories we observed is roughly congruent with the temporal scale of environmental change in the field.     

Less is more or more is less: Implications of glucose metabolism in the regulation of the reproductive potential and total lifespan of the Saccharomyces cerevisiae yeast

Carbohydrates are dietary nutrients that have an influence on cells physiology, cell reproductive capacity and, consequently, the lifespan of organisms. They are used in cellular processes after conversion to glucose, which is the primary source of energy and carbon skeleton for biosynthetic processes. Studies of the influence of glucose on cellular parameters and lifespan of organisms are primarily concerned with the effect of low glucose concentration defined as calorie restriction conditions. However, the effect of high glucose concentration on cell physiology is also very important. Thus, a comparative analysis of the effects of low and high glucose concentration conditions on cell efficiency was proposed with regard to reproductive capacity and total lifespan of the cell. Glucose concentration determines the type of metabolism and biosynthetic capabilities, which in turn, through the regulation on the cell size, may affect the reproductive capacity of cells. This study was conducted on yeast cells of wild-type and mutant strains Δgpa2 and Δgpr1 with glucose signalling pathway impairment. Such an experimental model enabled testing both the role of glucose concentration in the regulation of metabolic changes and the extent to which these changes depend on the extracellular or intracellular glucose concentrations. It has been shown here that calorie/glucose excess connected with changes in cell metabolic fluxes increases biosynthetic capabilities of yeast cells. This leads to an increase in cell dry weight accompanied by the increase in cell size and a simultaneous decrease in the reproductive potential and the overall length of cell life.