Genetics Could Explain Half of Human Lifespan Variation, Scientists Assert
For generations, individuals who reach remarkable ages have attributed their longevity to various factors, from a nightly dram of whisky to a life of caution. However, a groundbreaking new study suggests that the true secret to a long life may lie within our genes, with genetics potentially responsible for about 50% of the variation in human lifespan.
Unmasking the Genetic Contribution to Ageing
Published in the prestigious journal Science, this research addresses a critical gap in previous studies that attempted to decipher the genetic component of human lifespan. Earlier investigations often failed to account for extrinsic mortality, which includes deaths from accidents, violence, infectious diseases, and other external factors. As people age and become more frail, the risk of such extrinsic mortality increases, potentially obscuring the true genetic influence on longevity.
Led by Prof Uri Alon and his team at the Weizmann Institute of Science in Israel, the study focused on heritability—the proportion of variation in traits like lifespan within a population that can be attributed to genetics rather than environmental factors. Past estimates of heritability for human lifespan have varied widely, ranging from as low as 6% to 33%, but Alon and colleagues argue these figures are significant underestimates.
A Mathematical Model to Reveal Biological Ageing
To uncover the genetic signal, the researchers developed a sophisticated mathematical model that incorporates extrinsic mortality and the effects of biological ageing. They calibrated this model using historical datasets from thousands of twin pairs in Denmark and Sweden, analysing correlations in lifespan. By removing the impact of extrinsic mortality, the team isolated the contribution of biological ageing, which is driven by genetics.
The results are striking: approximately 50% of the variation in human lifespan appears to be due to genetics. This finding aligns with heritability levels observed in wild mice studied in laboratory settings, suggesting humans are not outliers in this regard. The remaining 50% of variation is likely influenced by a combination of random biological effects and environmental factors, such as lifestyle, diet, exercise, and social connections.
Validation and Implications for Future Research
The team validated their findings using data from a US study of siblings of centenarians, which also indicated a heritability of lifespan around 50%. Further analysis of Swedish datasets revealed that as extrinsic mortality declined over the 20th century—likely due to improvements in public health—the estimated genetic contribution to lifespan increased. This supports the idea that extrinsic mortality plays a key role in masking genetic effects when assessing heritability.
Prof Uri Alon expressed hope that this study will inspire deeper investigations into the specific genes that impact lifespan. "These genes will tell us the mechanisms that govern our internal clocks," he said. "They can one day be turned into therapy to slow down the rate of ageing and, in that way, slow down all age-related diseases at once."
Co-author Ben Shenhar emphasised the practical implications, noting that day-to-day experiences highlight genetics' role in longevity. "Around 20% of centenarians reach age 100 without serious debilitating illnesses," he explained, suggesting their genes may offer a protective effect. "Studies have identified many protective genes, but surely there are many still left to discover."
Expert Perspectives and Broader Context
While the study does not account for genes influencing the immune system, Prof Richard Faragher of the University of Brighton praised the research for indicating that humans are similar to other species in terms of lifespan heritability. "This gives you a certain amount of confidence that interventions that work in mice could carry over into humans," he remarked, highlighting potential future applications in ageing therapies.
In summary, this research reshapes our understanding of longevity by underscoring the substantial genetic component in human lifespan. It opens new avenues for exploring genetic mechanisms that could one day lead to innovative treatments for ageing and age-related conditions, while also acknowledging the continued importance of lifestyle and environmental factors in achieving a long and healthy life.
