Community Research and Development Information Service - CORDIS



Project ID: 260885
Funded under: FP7-IDEAS-ERC
Country: Sweden

Final Report Summary - AGINGSEXDIFF (Aging Differently: Understanding Sex Differences in Reproductive, Demographic and Functional Senescence)

Why do males and females have different lifespans? Why do they age differently? These questions have broad appeal because sex differences in life span and ageing are ubiquitous across the animal kingdom and represent a long-standing challenge in evolutionary biology. In most species, including humans, sexes differ not only in how long they live and when they start to senesce, but also in how they react to environmental interventions aimed at prolonging their lifespan or postponing the onset of ageing. Therefore, sex differences in lifespan and ageing have important implications beyond the questions posed by fundamental science. My goal here was to provide a general answer to the question “why do sexes age differently?” in the model organisms and, eventually, in humans. The key finding of this project is that sex differences in lifespan result from sex-specific selection.

We were able to provide first experimental support for a long-standing insight by George Williams that, all else being equal, the sex that experiences higher rate of extrinsic (non-ageing-related) mortality will evolve faster ageing. However, we were able to go beyond the test of the classic theory and to show that the source of extrinsic mortality (i.e. what kills the organisms) is at least as important, or perhaps even more important than the rate of extrinsic mortality (i.e. how often the organisms are killed). When extrinsic mortality is not random but rather selectively removes physiologically less robust individuals from the population, increased mortality results in the evolution of more physiologically robust and long-lived organisms.

Arguably, if we understand how sex differences in lifespan evolve, we should be able to shape them using experimental evolution approach. Indeed, we used experimental evolution to cause the evolution of sexual monomorphism in lifespan (i.e. both sexes have the same lifespan) in a species, which is naturally dimorphic for this trait (i.e. males and females have different lifespans). Alternatively, we used a different selection regime to cause an increase in sex difference in lifespan in other experimental populations of the same species. We thus showed how evolutionary malleable are sex differences in lifespan and that we can use the fundamental principles of the evolutionary theory to predict the direction of the response depending on the type of selection we apply in each sex.

The aforementioned studies show that there is plenty of sex-specific genetic variation for lifespan in males and females. Nevertheless, much of the genetic variation for lifespan is shared between the sexes. Because males and females have different reproductive strategies, gene variants that confer long-life can result in increased fitness in one sex but decreased fitness in the other sex. Such genetic sexual antagonism helps maintaining genetic variation for lifespan but also is predicted to result in sex-specific responses to pharmacological treatments aimed at lifespan extension.

Finally, we used these ideas to increase our understanding of sex differences in human lifespan using a historical human population in Utah during the hundred years of demographic transition to modern lifestyle, which is characterised, among many other aspects, by gradual reduction in fertility. We showed that initially males lived longer than females, but while female lifespan increased substantially during the demographic transition, male lifespan remained largely stable, eventually resulting in female-biased longevity. This was because females, but not males, payed the longevity cost of reproduction at high parities and, therefore, females likely benefited more than males from reduced fertility during the demographic transition. This suggests that biological differences in the longevity costs of reproduction between the sexes, superimposed on the cultural change during the demographic transition, resulted in female-biased lifespan in the modern society.

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