Research: Longevity Brings Unavoidable Risks for All Humans

A recent study has shed light on why extended human lifespan is frequently accompanied by deteriorating health, suggesting the ‘price’ of longevity is rooted in evolutionary biology. Published in the journal Nature Reviews Genetics, the research examines the concept of ‘selection shadow’, a mid-20th-century theory now supported by large-scale modern genetic data. The theory posits that the power of natural selection diminishes with age. Evolution is most effective at maintaining bodily functions during the reproductive years. Once an individual passes the age of having offspring, evolutionary pressure becomes very weak, allowing harmful mutations or genes detrimental in old age to persist without being naturally eliminated. Two main mechanisms explain this risk. The first is the accumulation of harmful mutations; genetic changes whose effects only appear in later life are not detected by natural selection and are thus passed down and accumulate over generations. The second is genetic trade-offs, where certain genes highly beneficial in youth, for instance by supporting fertility and growth, can increase the risk of diseases like cancer or chronic inflammation in old age. Evolution retains these genes because the benefits in early life far outweigh the detriments that appear much later. Researchers Handan Melike Dönertaş and Linda Partridge analysed genetic data from hundreds of thousands of people and found strong evidence supporting this concept in humans. Dönertaş from the Fritz Lipmann Institute in Germany explained that genomic advances allowed them to prove that genes involved in chronic inflammation, stem cell exhaustion, and organ decline are not effectively selected against after reproductive age. A concrete example is a genetic variant that aids fertility in one’s 20s and 30s but increases the risk of heart disease or cancer after the age of 60. From an evolutionary perspective, such a cancer-linked gene is retained because it ensures the continuation of the species. The findings are shifting research goals away from simply extending lifespan towards prolonging the period of healthy life, known as healthspan. Further studies on long-lived animals, such as the naked mole-rat, are underway to understand how they overcome this ‘selection shadow’, with the aim of applying these insights to humans.