DOES INCREASED MORTALITY FAVOR THE EVOLUTION OF MORE RAPID SENESCENCE?

It is widely believed (following the 1957 hypothesis of G. C. Williams) that greater rates of “extrinsic” (age- and condition-independent) mortality favor more rapid senescence. However, a recent analysis of mammalian life tables failed to find a significant correlation between minimum adult mortality rate and the rate of senescence. This article presents a simple theoretical analysis of how extrinsic mortality should affect the rate of senescence (i.e., the rate at which probability of mortality increases with age) under different evolutionary and population dynamical assumptions. If population dynamics are density independent, extrinsic mortality should not alter the senescence rate favored by natural selection. If population growth is density dependent and populations are stable, the effect of extrinsic mortality depends on the age specificity of the density dependence and on whether survival or reproduction (or both) are functions of density. It is possible that higher extrinsic mortality will increase the rate of senescence at all ages, decrease the rate at all ages, or increase it at some ages while decreasing it at others. Williams's hypothesis is most likely to be supported when density dependence acts primarily on fertility and does not differentially decrease the fertilities of older individuals. Patterns contrary to Williams's prediction are possible when density dependence acts primarily on the survival or fertility of later ages or when most variation in mortality rates is due to variation in nonextrinsic mortality.     

HAS ACTUARIAL AGING “SLOWED” OVER THE PAST 250 YEARS? A COMPARISON OF SMALL‐SCALE SUBSISTENCE POPULATIONS AND EUROPEAN COHORTS

G.C. Williams's 1957 hypothesis famously argues that higher age-independent, or "extrinsic," mortality should select for faster rates of senescence. Long-lived species should therefore show relatively few deaths from extrinsic causes such as predation and starvation. Theoretical explorations and empirical tests of Williams's hypothesis have flourished in the past decade but it has not yet been tested empirically among humans. We test Williams's hypothesis using mortality data from subsistence populations and from historical cohorts from Sweden and England/Wales, and examine whether rates of actuarial aging declined over the past two centuries. We employ three aging measures: mortality rate doubling time (MRDT), Ricklefs's ω, and the slope of mortality hazard from ages 60–70, m '_60–70, and model mortality using both Weibull and Gompertz–Makeham hazard models. We find that (1) actuarial aging in subsistence societies is similar to that of early Europe, (2) actuarial senescence has slowed in later European cohorts, (3) reductions in extrinsic mortality associate with slower actuarial aging in longitudinal samples, and (4) men senesce more rapidly than women, especially in later cohorts. To interpret these results, we attempt to bridge population-based evolutionary analysis with individual-level proximate mechanisms.     

Condition‐dependent mortality exacerbates male (but not female) reproductive senescence and the potential for sexual conflict

Disentangling the relationship between age and reproduction is central to understand life‐history evolution, and recent evidence shows that considering condition‐dependent mortality is a crucial piece of this puzzle. For example, nonrandom mortality of ‘low‐condition’ individuals can lead to an increase in average lifespan. However, selective disappearance of such low‐condition individuals may also affect reproductive senescence at the population level due to trade‐offs between physiological functions related to survival/lifespan and the maintenance of reproductive functions. Here, we address the idea that condition‐dependent extrinsic mortality (i.e. simulated predation) may increase the age‐related decline in male reproductive success and with it the potential for sexual conflict, by comparing reproductive ageing in Drosophila melanogaster male/female cohorts exposed (or not) to condition‐dependent simulated predation across time. Although female reproductive senescence was not affected by predation, male reproductive senescence was considerably higher under predation, due mainly to an accelerated decline in offspring viability of ‘surviving’ males with age. This sex‐specific effect suggests that condition‐dependent extrinsic mortality can exacerbate survival‐reproduction trade‐offs in males, which are typically under stronger condition‐dependent selection than females. Interestingly, condition‐dependent extrinsic mortality did not affect mating success, hinting that accelerated reproductive senescence is due to a decrease in male post‐copulatory fitness components. Our results support the recent proposal that male ageing can be an important source of sexual conflict, further suggesting this effect could be exacerbated under more natural conditions.     

Reports of the Death of Extrinsic Mortality Moulding Senescence Have Been Greatly Exaggerated

The classic evolutionary theory of aging posits that senescence evolves because the weakening of selection with age allows mutations with late-acting deleterious effects to accumulate. Because extrinsic mortality is an important cause of weakening selection, the central prediction of the theory has been that higher extrinsic mortality should lead to the evolution of a higher rate of senescence. However, the validity of this prediction has been questioned, even to the extent of suggesting that it is not a prediction of the theory at all, primarily on the basis that changes in population growth rate will compensate for changes in extrinsic mortality. The implication is that empiricists have been using the wrong prediction to test the theory. This claim is misleading, however, because it does not apply on an evolutionary timescale, when population size must be roughly constant. With a constant population size, Hamilton’s fitness sensitivities show that extrinsic mortality determines the rate at which the strength of selection declines with age, and thus determines the rate of senescence. The central prediction has been confirmed in the few controlled experiments with model organisms that have been conducted, but clearly this is an area ripe for further investigation.     

Effects of Extrinsic Mortality on the Evolution of Aging: A Stochastic Modeling Approach

The evolutionary theories of aging are useful for gaining insights into the complex mechanisms underlying senescence. Classical theories argue that high levels of extrinsic mortality should select for the evolution of shorter lifespans and earlier peak fertility. Non-classical theories, in contrast, posit that an increase in extrinsic mortality could select for the evolution of longer lifespans. Although numerous studies support the classical paradigm, recent data challenge classical predictions, finding that high extrinsic mortality can select for the evolution of longer lifespans. To further elucidate the role of extrinsic mortality in the evolution of aging, we implemented a stochastic, agent-based, computational model. We used a simulated annealing optimization approach to predict which model parameters predispose populations to evolve longer or shorter lifespans in response to increased levels of predation. We report that longer lifespans evolved in the presence of rising predation if the cost of mating is relatively high and if energy is available in excess. Conversely, we found that dramatically shorter lifespans evolved when mating costs were relatively low and food was relatively scarce. We also analyzed the effects of increased predation on various parameters related to density dependence and energy allocation. Longer and shorter lifespans were accompanied by increased and decreased investments of energy into somatic maintenance, respectively. Similarly, earlier and later maturation ages were accompanied by increased and decreased energetic investments into early fecundity, respectively. Higher predation significantly decreased the total population size, enlarged the shared resource pool, and redistributed energy reserves for mature individuals. These results both corroborate and refine classical predictions, demonstrating a population-level trade-off between longevity and fecundity and identifying conditions that produce both classical and non-classical lifespan effects.     

Toward reconciling inferences concerning genetic variation in senescence in Drosophila melanogaster.

Standard models for senescence predict an increase in the additive genetic variance for log mortality rate late in the life cycle. Variance component analysis of age-specific mortality rates of related cohorts is problematic. The actual mortality rates are not observable and can be estimated only crudely at early ages when few individuals are dying and at late ages when most are dead. Therefore, standard quantitative genetic analysis techniques cannot be applied with confidence. We present a novel and rigorous analysis that treats the mortality rates as missing data following two different parametric senescence models. Two recent studies of Drosophila melanogaster, the original analyses of which reached different conclusions, are reanalyzed here. The two-parameter Gompertz model assumes that mortality rates increase exponentially with age. A related but more complex three-parameter logistic model allows for subsequent leveling off in mortality rates at late ages. We find that while additive variance for mortality rates increases for late ages under the Gompertz model, it declines under the logistic model. The results from the two studies are similar, with differences attributable to differences between the experiments.     

Early onset of reduced reproductive performance with age in the Treecreeper (Certhia familiaris)

Reductions in reproductive performance with age have been predicted to result from a general deterioration of performance, i.e. senescence. Variation among species in the onset and rate of this deterioration depends on the age-independent extrinsic mortality rate. If few individuals reach a specific age, the strength of selection for mechanisms that retard senescence will be reduced. The aim of this study was to investigate the age-dependent variation in two reproductive traits in a species, the Treecreeper (Certhia familiaris), with a low between-year survival rate. Clutch size did not vary with age, but egg size decreased from the first to the second breeding season. Compared with published age-dependent reductions in egg size, Treecreepers demonstrate the earliest onset of senescence, but they also have the highest total mortality rate, corroborating the predictions from the evolutionary theory of senescence. Production of eggs seems to be demanding for female Treecreepers, as egg size is also positively dependent on ambient temperature, further stressing the vulnerability of this trait for small reductions in female performance.     

Rapid senescence in pacific salmon

Any useful evolutionary theory of senescence must be able to explain variation within and among natural populations and species. This requires a careful characterization of age-specific mortality rates in nature as well as the intrinsic and extrinsic factors that influence these rates. We perform this task for two populations of semelparous Pacific salmon. During the breeding season, estimated daily mortality rates increased from 0 to 0.2-0.5 (depending on the year) over the course of several weeks. Early-arriving individuals had a later onset and/or a lower rate of senescence in each breeding season, consistent with adaptive expectations based on temporal variation in selection. Interannual variation in senescence was large, in part because of extrinsic factors (e.g., water temperature). Predation rates were higher in Pick Creek sockeye salmon (anadromous Oncorhynchus nerka) than in Meadow Creek kokanee (nonanadromous O. nerka), but in contrast to evolutionary theory, senescence was not more rapid in the former. Interannual variation may have obscured interpopulation divergence in senescence. Pacific salmon are a promising system for further studies on the physiological, evolutionary, and genetic bases of senescence. In particular, we encourage further research to disentangle the relative importance of adaptive and nonadaptive variation in senescence.     

Disease spread in age structured populations with maternal age effects

Fundamental ecological processes, such as extrinsic mortality, determine population age structure. This influences disease spread when individuals of different ages differ in susceptibility or when maternal age determines offspring susceptibility. We show that Daphnia magna offspring born to young mothers are more susceptible than those born to older mothers, and consider this alongside previous observations that susceptibility declines with age in this system. We used a susceptible‐infected compartmental model to investigate how age‐specific susceptibility and maternal age effects on offspring susceptibility interact with demographic factors affecting disease spread. Our results show a scenario where an increase in extrinsic mortality drives an increase in transmission potential. Thus, we identify a realistic context in which age effects and maternal effects produce conditions favouring disease transmission.     

Age-dependent terminal declines in reproductive output in a wild bird

In many iteroparous species individual fitness components, such as reproductive output, first increase with age and then decline during late-life. However, individuals differ greatly in reproductive lifespan, but reproductive declines may only occur in the period just before their death as a result of an age-independent decline in physiological condition. To fully understand reproductive senescence it is important to investigate to what extent declines in late-life reproduction can be explained by age, time until death, or both. However, the study of late-life fitness performance in natural populations is challenging as the exact birth and death dates of individuals are often not known, and most individuals succumb to extrinsic mortality before reaching old age. Here, we used an exceptional long-term longitudinal dataset of individuals from a natural, closed, and predator-free population of the Seychelles warbler (Acrocephalus sechellensis) to investigate reproductive output, both in relation to age and to the time until the death of an individual (reverse-age approach). We observed an initial age-dependent increase in reproductive output that was followed by a decline in old age. However, we found no significant decline in reproductive output in the years directly preceding death. Although post-peak reproductive output declined with age, this pattern differed between terminal and non-terminal reproductive attempts, and the age-dependence of the terminal breeding attempt explained much of the variation in age-specific reproductive output. In fact, terminal declines in reproductive output were steeper in very old individuals. These results indicate that not only age-dependent, but also age-independent factors, such as physiological condition, need to be considered to understand reproductive senescence in wild-living animals.     

Interaction Mortality: Senescence May Have Evolved because It Increases Lifespan

Given an extrinsic challenge, an organism may die or not depending on how the threat interacts with the organism''s physiological state. To date, such interaction mortality has been only a minor factor in theoretical modeling of senescence. We describe a model of interaction mortality that does not involve specific functions, making only modest assumptions. Our model distinguishes explicitly between the physiological state of an organism and potential extrinsic, age-independent threats. The resulting mortality may change with age, depending on whether the organism''s state changes with age. We find that depending on the physiological constraints, any outcome, be it ‘no senescence’ or ‘high rate of senescence’, can be found in any environment; that the highest optimal rate of senescence emerges for an intermediate physiological constraint, i.e. intermediate strength of trade-off; and that the optimal rate of senescence as a function of the environment is driven by the way the environment changes the effect of the organism''s state on mortality. We conclude that knowledge about the environment, physiology and their interaction is necessary before reasonable predictions about the evolution of senescence can be made.     

Quantitative genetic tests of recent senescence theory: age-specific mortality and male fertility in Drosophila melanogaster

Quantitative genetic models of aging predict that additive genetic variance for fitness components should increase with age. However, recent studies have found that at very late ages, the genetic variance components decline. This decline may be due to an age-related drop in reproductive effort. If genetic variance in reproductive effort affects the genetic variance in mortality, the decline in reproductive effort at late ages should lead to a decrease in the genetic variance in mortality. To test this, we carried out a large-scale quantitative genetic analysis of age-specific mortality and fertility in virgin male Drosophila melanogaster. As in earlier studies, we found that the additive variance for age-specific mortality and fertility declined at late ages. Also, recent theoretical developments provide new predictions to distinguish between the mutation accumulation (MA) and antagonistic pleiotropy (AP) models of senescence. The deleterious effects of inbreeding are expected to increase with age under MA, but not under AP. This prediction was supported for both age-specific mortality and male fertility. Under AP, the ratio of dominance to additive variance is expected to decline with age. This predicition, too, was supported by the data analyzed here. Taken together, these analyses provide support for both the models playing a role in the aging process. We argue that the time has come to move beyond a simple comparison of these genetic models, and to think more deeply about the evolutionary causes and consequences of senescence.     

EXPERIMENTAL EVOLUTION OF SENESCENCE: AN ANALYSIS USING A “HETEROGENEITY” MORTALITY MODEL

A long-term laboratory selection experiment has produced replicated populations of fruit flies that differ in mean life span by more than twofold. An analysis of age-specific mortality rates indicated that differences in mean life span have been achieved principally by evolution of patterns of senescence. These results provide empirical confirmation that senescence can be modified within species by appropriate forms of natural selection, which is a fundamental prediction of theories regarding the genetic basis and evolution of senescence. Mortality data were fit to a model that accounts for the leveling off of cohort mortality rates at older ages, but that does not necessarily imply that very old individuals cease to senesce.     

Size-mediated ageing reduces vigour in trees

There is increasing interest in understanding the costs and benefits of increased size and prolonged lifespan for plants. Some species of trees can grow more than 100 m in height and can live for several millennia, however whether these achievements are obtained at the cost of some other physiological functions is currently unclear. As increases in size are usually associated with ageing, it is also unclear whether observed reductions in growth rates and increased mortality rates are a function of size or of age per se. One theory proposes that reduced growth after the start of the reproductive phase is caused by cellular senescence. A second set of theories has focussed instead on plant size and the increased respiratory burdens or excessive height. We report on experimental manipulations to separate the effects of extrinsic factors such as size from those of intrinsic factors such as age for four tree species of contrasting phylogeny and life history. For each species, we measured growth, gas exchange and leaf biochemical properties for trees of different ages and sizes in the field and on propagated material obtained from the same genetic individuals but now all of small similar size in our common gardens. For all species, evidence indicated that size, not cellular senescence, accounted for the observed age‐related declines in relative growth rates and net assimilation rates. Two species exhibited evidence of genetic control on leaf characters such as specific leaf area, although size also exerted an independent, and stronger, effect. We found partial support for the theory of hydraulic limitations to tree growth. The lack of a marked separation of soma and germline, an unlimited proliferation potential of meristem cells and the exponential increase in reproductive effort with size all help explain the lack of a senescence‐induced decline in trees. It is possible that trees much older than the ones we sampled exhibit senescence symptoms.     

Senescence in relation to latitude and migration in birds

Senescence is the age‐related deterioration of the phenotype, explained by accumulation of mutations, antagonistic pleiotropy, free radicals or other mechanisms. I investigated patterns of actuarial senescence in a sample of 169 species of birds in relation to latitude and migration, by analysing longevity records adjusted for sampling effort, survival rate and body mass. Senescence might decrease at low latitudes because of elevated adult survival rates and generally slow life histories. Alternatively, the rate of senescence might increase at low latitudes because of the greater impact of biological interactions such as parasitism, predation and competition on fitness through differential effects of age‐specific mortality (e.g. because immunologically naïve young individuals and immuno‐senescent old individuals might die more frequently than individuals belonging to intermediate age classes). Bird migration entails extensive exercise twice annually, with migrants spending more time in benign environments with little abiotic mortality than residents, migrants having higher adult survival rate and lower annual fecundity than residents, and migrants suffering more from the consequences of oxidative stress than residents. The rate of senescence increased with latitude, as expected because of slow life histories at low latitudes. Independently, rate of senescence decreased with increasing migration distance. These findings were robust to control for potentially confounding effects of body mass, age of first reproduction and phenotypic similarity among species because of common descent.     

The senescence of Daphnia from risky and safe habitats

Evaluating life history in an ecological context is critical for understanding the diversity of life histories found in nature. Lifespan and senescence differ greatly among taxa, but their ecological context is not well known. Life history theory proposes that senescence is ultimately caused by a reduction of the effectiveness of natural selection as organisms age. A key prediction is that different levels of extrinsic mortality risk lead to the evolution of different senescence patterns. I quantified both mortality risk and investment in late-life fitness of Daphnia pulex-pulicaria , a common freshwater zooplankter. I found that Daphnia from high-risk pond habitats invest relatively little in late-life fitness, whereas those from low-risk lake habitats invest relatively more in late-life fitness. This suggests that ecological approaches can be useful for understanding senescence variation.     

The evolution of senescence through decelerating selection for system reliability

Senescence is a universal phenomenon in organisms, characterized by increasing mortality and decreasing fecundity with advancing chronological age. Most proximate agents of senescence, such as reactive oxygen species and UV radiation, are thought to operate by causing a gradual build-up of bodily damage. Yet most current evolutionary theories of senescence emphasize the deleterious effects of functioning genes in late life, leaving a gap between proximate and ultimate explanations. Here, we present an evolutionary model of senescence based on reliability theory, in which beneficial genes or gene products gradually get damaged and thereby fail, rather than actively cause harm. Specifically, the model allows organisms to evolve multiple redundant copies of a gene product (or gene) that performs a vital function, assuming that organisms can avoid condition-dependent death so long as at least one copy remains undamaged. We show that organisms with low levels of extrinsic mortality, and high levels of genetic damage, tend to evolve high levels of redundancy, and that mutation-selection balance results in a stable population distribution of the number of redundant elements. In contrast to previous evolutionary models of senescence, the mortality curves that emerge from such populations match empirical senescence patterns in three key respects: they exhibit: (1) an initially low, but rapidly increasing mortality rate at young ages, (2) a plateau in mortality at advanced ages and (3) 'mortality compensation', whereby the height of the mortality plateau is independent of the environmental conditions under which different populations evolved.     

Repeated intraspecific divergence in life span and aging of African annual fishes along an aridity gradient

Life span and aging are substantially modified by natural selection. Across species, higher extrinsic (environmentally related) mortality (and hence shorter life expectancy) selects for the evolution of more rapid aging. However, among populations within species, high extrinsic mortality can lead to extended life span and slower aging as a consequence of condition‐dependent survival. Using within‐species contrasts of eight natural populations of Nothobranchius fishes in common garden experiments, we demonstrate that populations originating from dry regions (with short life expectancy) had shorter intrinsic life spans and a greater increase in mortality with age, more pronounced cellular and physiological deterioration (oxidative damage, tumor load), and a faster decline in fertility than populations from wetter regions. This parallel intraspecific divergence in life span and aging was not associated with divergence in early life history (rapid growth, maturation) or pace‐of‐life syndrome (high metabolic rates, active behavior). Variability across four study species suggests that a combination of different aging and life‐history traits conformed with or contradicted the predictions for each species. These findings demonstrate that variation in life span and functional decline among natural populations are linked, genetically underpinned, and can evolve relatively rapidly.     

When being alive implies being safe: variation in mortality rates can cause oviposition selectivity to increase with age

Optimal behavioural decisions are expected to depend on various state variables, such as physiological condition or age. In insects, empirical evidence of the effect of adult age on oviposition selectivity is mixed. Consistently, optimality models – which primarily incorporate the effects of egg load and senescence – fail to provide universal predictions. Here we propose that spatial variation in mortality rates creates an additional mechanism able to select for an increase in selectivity with age. Females can be selected to use the fact of having reached an advanced age as a cue of low mortality rates in their environment. Older females may thus be less time-limited, and can afford for more careful host selection. This is because variation in mortality rates can cause a positive correlation between individual age, and expected residual life span. We present a simulation model that formalises the verbal argument presented above, and discuss the findings in the more general context of the dependence of reproductive output on age.