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 a new study from the Weizmann Institute of Science, published today 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 Prof. 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.
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Up to age 80, the risk of dying from dementia shows a heritability of about 70 percent - far higher than that of cancer or heart disease.
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 skepticism about the role of genetics in aging and about the feasibility of identifying genetic determinants of longevity," says 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."
Prof. Uri Alon's research is supported by the Sagol Institute for Longevity Research; the Knell Family Institute for Artificial Intelligence; the Moross Integrated Cancer Center; the David and Fela Shapell Family Center for Genetic Disorders Research; the Zuckerman STEM Leadership Program; and the Rising Tide Foundation.
Prof. Alon is the incumbent of the Abisch-Frenkel Professorial Chair.
