Mutation and the evolution of ageing: from biometrics to system genetics

Abstract

A notable success for evolutionary genetics during the past century was to generate a coherent, quantitative explanation for an apparent evolutionary paradox: the tendency for multicellular organisms to show declining fitness with age (senescence, often referred to simply as 'ageing'). This general theory is now widely accepted and explains most of the features of senescence that are observed in natural and laboratory populations, but specific instantiations of that theory have been more controversial. To date, most of the empirical tests of these models have relied on data generated from biometric experiments. Modern population genetics and genomics provide new, and probably more powerful, ways to test ideas that are still controversial more than half a century after the original theory was developed. System-genetic experiments have the potential to address both evolutionary and mechanistic questions about ageing by identifying causal loci and the genetic networks with which they interact. Both the biometrical approaches and the newer approaches are reviewed here, with an emphasis on the challenges and limitations that each method faces.

Figure 1.

(a) The demographic parameters for a hypothetical non-senescing population, as imagined by Hamilton (1966). Age-specific survival is constant, and cumulative survival declines geometrically. Age-specific reproduction rates are constant after the age of first reproduction, which in this case is age-class 12. (b) Hamilton's sensitivity functions, which reflect the strength of natural selection in the population described in (a). The symbols in the sensitivity functions represent terms from the discrete version of the Euler–Lotka equation, where r is the intrinsic rate of increase, l(x) is the probability of survival to age x, m(x) is the expected number of offspring produced by an individual of age x and T is a measure of generation time. (a) Dashed line, age-specific survival; black line, cumulative survival; grey line, age-specefic fecundity. (b) Black line, selection on survival; grey line, selection on fertility.