Why we age.

Three categories of explanations exist for why we age: mechanistic theories, which omit reference to evolutionary forces; weakening force of selection theories, which posit that barriers exist that prevent evolutionary forces from optimising fitness in ageing; and optimisation theories, which posit that evolutionary forces actually select for ageing under the constraints that exist due to limited energy and other resources. We now have a broad data set of observed features of ageing against which these categories of theories can be tested, including results of interventions like caloric restriction, features of long-lived organisms, the existence of mortality rate plateaus, longevity of eusocial insect queens, and the malleability of lifespan. Optimisation theories are the only ones that fit all the observed data. Moreover, this category of theory makes a very ordinary claim, consistent with significant other data: evolution by natural selection is operating in ageing. It is actually quite extraordinary, either implicitly or explicitly, to claim that natural selection fails to operate, as the other categories of theories do. A key prediction of optimisation theories that differs from other theories is that mutations that extend lifespan should generally reduce fitness under natural conditions. Contrary to some suggestions in the literature, to date the available evidence supports this prediction. Optimisation theories have several implications, including that lifespan should be relatively easy to manipulate by tapping into existing biological mechanisms, and that the geroscience hypothesis, which states that intervention on the rate of ageing should also modulate the incidence of age-related diseases, is likely to be correct.