A review article now published in “Nature Reviews Genetics” brings together evolutionary theory, comparative genomics and large-scale human genetics to explain why we age and why ageing rates differ among individuals and species. The two authors—from the Leibniz Institute on Aging—Fritz Lipmann Institute (FLI) in Jena and University College London in London—describe how, because modern humans now routinely survive into old age, we live with the late-life consequences of biological pathways that natural selection optimized for youth, and of harmful mutations that act too late in life for selection to clear them efficiently. Reading ageing through this evolutionary lens also clarifies why age-related diseases share genetic roots — and points to targeting a small set of ancient, conserved pathways to counter several of them at once.

Jena/London. The reason why and how organisms age is one of the central questions in biology. Classical evolutionary theories explain aging primarily by the fact that natural selection becomes less effective with age. This means that traits are particularly important for evolution when they influence reproduction. In early life, therefore, advantageous traits are strongly “selected”; but selection acts only weakly on traits whose effects appear in old age, because by then many organisms have stopped reproducing. As a result, harmful effects that act only late in life are barely removed by selection and can build up over evolutionary time. This effect is described as the “selection shadow” and forms the basis of modern evolutionary theories of aging.

Added to this are so-called trade-offs—conflicts of interest within the body—such as the energy that an organism has at its disposition. This energy is limited, meaning the organism must allocate it between reproduction and maintaining the body. Individuals who have many offspring early in life often invest less in long-term repair processes, which can lead to the body aging more rapidly.

At the genetic level, two key mechanisms explain ageing: First, through so-called mutation accumulation, in which harmful genetic variants that only take effect late in life are only weakly removed by selection. Second, through antagonistic pleiotropy, in which genes have beneficial effects in early life but can contribute to the development of diseases in old age.

The evolution of aging – Past and Present

The new review article in “Nature Reviews Genetics” broadens this perspective and examines how the evolution of aging plays out under the conditions of modern human society. In these societies, people live significantly longer, have fewer children, and receive better medical care. At the center of this is the so-called demographic transition, namely the shift from societies with high birth and death rates to those with low birth rates and high life expectancy.

Under these conditions, the classic predictions become even more relevant: because far more people survive into old age today than at any earlier point in human evolution, the consequences of the selection shadow — the accumulation of late-acting harmful variants, and youth-optimized pathways that remain active in later life — are now experienced on a scale that selection never acted against. Modern living conditions add a further dimension: abundant food, less physical activity and modern medicine differ markedly from the environments in which human biology evolved, and can unmask trade-offs that previously carried no visible cost.

According to Dr. Melike Dönertaş of the Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) in Jena and Dame Linda Partridge of University College London, UK, this does not mean old age is now under selection the way youth once was longer survival extends selection's reach into later life, but fewer births lower its overall strength. The net result is that biological processes barely touched by selection in the evolutionary past now shape the lives of large numbers of people.

Aging is the result of several factors working together

Ageing, the Review argues, cannot be reduced to a single cause. It emerges from the interplay of genetic make-up, life history, environmental conditions and population structure — and modern demographic and environmental conditions change which of its consequences we actually live long enough to experience.

At the molecular level, it is evident that aging is characterized by a series of conserved biological processes known as the “hallmarks of aging.” These include, among other things, changes in DNA stability, loss of mitochondrial function, impaired nutrient metabolism, and the accumulation of damaged proteins and aging cells. These processes are regulated by key signaling pathways such as the insulin/IGF-1 system or the mTOR signaling pathway, which control growth, energy balance, and repair mechanisms. It is noteworthy that these mechanisms are conserved across many species, suggesting that aging arises from fundamental biological systems that were originally optimized for growth and reproduction and continue to function in later life. The Review compiles genomic data showing that genes linked to these hallmarks, and to longevity more broadly, are unusually conserved between humans and other animals.

Aging as a result of social developments

This perspective forges new connections between various fields of research: evolutionary biology, demography, and biomedical research. This means that aging is no longer viewed only as a biological process within the body, but also as a result of societal developments. This is particularly important for understanding age-related diseases—that is, conditions that primarily occur in older age, such as cardiovascular diseases or neurodegenerative diseases. This perspective helps explain why such diseases are so prevalent in modern societies and how they may have co-evolved. Many of these diseases share common biological causes and arise from the same fundamental aging processes.

“An evolutionary view of ageing isn't just a historical curiosity - it points to the conserved, ancient pathways whose continued activity in later life contributes to age-related disease, and where interventions are therefore most likely to work.” emphasizes Dr. Dönertaş.

“Furthermore, it also reframes the goal: not simply extending lifespan, but partially relieving the late-life costs of a biology that natural selection optimized for early life - so that more of life is spent in good health,” explains the British geneticist, Professor Dame Linda Partridge, Founding Director of the Max Planck Institute for Biology of Ageing in Cologne, Honorary Professor at University College London (UCL), as well as member of the FLI’s Scientific Advisory Board.

An integrative framework

The Review draws these strands together into a single framework — one linking evolutionary theory, the molecular biology of ageing, and the demographic and environmental conditions of modern life. The argument is that the modern context is not merely a backdrop to ageing but part of why its late-life costs are now experienced so widely — and that an evolutionary lens is what makes those costs interpretable, and potentially addressable.

Building on this foundation, future research could more specifically investigate demographic changes—such as rising life expectancy, lower birth rates, or an aging population—directly impact molecular and physiological aging processes. These include, for example, changes in cellular aging, tissue repair, metabolic regulation, and the risk of age-related diseases. At the same time, current genetic studies show that aging is a highly complex, polygenic trait involving numerous genes, each with small effects. This opens up new perspectives both for basic research and for understanding aging processes in an increasingly aging global population.

Publication
Evolutionary genetics of ageing. Dönertaş HM, Partridge L. Nat Rev Genet. 2026, May 11. doi: 10.1038/s41576-026-00959-x. https://www.nature.com/articles/s41576-026-00959-x