Rethinking Longevity: Genes Matter More than We Thought

A new Weizmann Institute of Science study has found that the genetic contribution to human lifespan is about 50 percent – more than double previous estimates.

What determines how long we live – and to what extent is our lifespan shaped by our genes? Surprisingly, for decades scientists believed that the heritability of human lifespan was relatively low compared to other human traits, standing at just 20 to 25 percent; some recent large-scale studies even placed it below 10 percent.

Now the Weizmann study, recently published in Science, presents an entirely different picture.

According to the findings, genetics accounts for about 50 percent of variation in human lifespan – twice as much, or more, than previously thought. The study was led by Ben Shenhar from the lab of Professor Uri Alon of Weizmann’s Molecular Cell Biology Department.

Using mathematical models and analyses of three large twin databases from Sweden and Denmark – including, for the first time in this context, a dataset of twins who were raised apart – the researchers showed that earlier heritability estimates were masked by high levels of extrinsic mortality, such as deaths caused by accidents, infections and environmental hazards.

Filtering out such extrinsic factors was impossible in historic datasets because they provided no information about the cause of death. To compensate for this limitation, the researchers developed an innovative framework that included mathematical simulation of virtual twins to separate deaths due to biological aging from those caused by extrinsic factors.

The new results are consistent with the heritability of other complex human traits and with findings from animal models.

The results have far-reaching implications for aging research and public health.

“For many years, human lifespan was thought to be shaped almost entirely by non-genetic factors, which led to considerable scepticism about the role of genetics in aging and about the feasibility of identifying genetic determinants of longevity,” said Shenhar.

“By contrast, if heritability is high, as we have shown, this creates an incentive to search for gene variants that extend lifespan, in order to understand the biology of aging and, potentially, to address it therapeutically.”

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