Evolutionary genetics of ageing

Abstract

Modern humans now routinely survive to advanced ages, in far greater proportions than ancestral populations, and thus experience the consequences of molecular pathways optimized for youth yet still active in old age. Natural selection weakens over the course of adulthood, creating a selection ‘shadow’ in which deleterious late-acting mutations accumulate and alleles with early-life benefits persist despite late-life costs. An evolutionary lens helps us to understand puzzling patterns — from conserved longevity pathways spanning the tree of life to a 100-fold variation in maximum lifespan across vertebrates — and explains why age-related diseases share genetic architectures. Advances in comparative genomics, large-scale human genetic studies and multi-omics ageing biomarkers now enable rigorous testing of evolutionary predictions. This Review integrates evolutionary genetics with molecular mechanisms to clarify why ageing evolves, how it varies across species and individuals, and how these insights can guide healthspan extension. Modern humans increasingly live long enough to experience late-life consequences of genetic and molecular systems shaped by natural selection. In this Review, the authors integrate evolutionary genetics and genetic evidence to explain why ageing evolves, why longevity varies across species and individuals, and how these insights inform healthspan extension.