Senescence and Ageing

Abstract

Ageing, or senescence, is the decline in fitness components caused by the progressive deterioration of virtually all physiological functions. Given the direct fitness costs of ageing, and the rich history of evolutionary and biomedical studies on the topic, it fits well within the framework of evolutionary medicine. This chapter explores the history of evolutionary studies of ageing, but attempts to integrate this rich literature with proximate, molecular studies of ageing. Evolutionary biologists have long seen ageing not as an adaptive process, but rather as the inevitable outcome of natural selection’s inability to eliminate alleles that are associated with deleterious effects if these effects occur at later ages. This principle underlies two complementary theories. First, germline mutations that do not affect fitness early in life but show deleterious effects at late ages will accumulate over evolutionary time, leading to increased ageing (the ‘mutation accumulation’ theory). Second, selection would actually favour late-acting deleterious mutations if they conferred early-acting beneficial effects (the ‘antagonistic pleiotropy’ theory). This chapter discusses the rationale behind these theories and the challenges facing efforts to test them. It discusses a variety of proximate mechanisms thought to underlie ageing, including environmental, genetic, and epigenetic factors, placing these in an evolutionary context and exploring the possibility that proximate mechanisms might provide us with a biological clock. Finally, it explores three of the most common pathophysiological processes associated with ageing—cancer, cardiovascular disease, and neurodegenerative disease—and the potential to decrease or delay onset of these major age-related drivers of ageing.