What influences how long we live, and how much of that influence is written into our genes? Scientists long believed that genetics played only a modest role. Previous estimates suggest that genetic factors explain about 20 to 25 percent of the difference in lifespan, and some large studies even put the number at less than 10 percent.
New research from the Weizmann Institute of Science reveals that sciencecalling into question that long-held view. Researchers report that roughly half of the variation in human lifespan can be attributed to genetics, at least twice as much as previous estimates. The research was led by Ben Shenhar in the laboratory of Professor Uri Aron in the Department of Molecular and Cellular Biology at Weizmann University.
“For many years, longevity was thought to be primarily due to non-genetic factors, leading to growing skepticism about the genetic determinants of longevity.”
Why previous estimates were off the mark
To reach this conclusion, the team analyzed three extensive twin databases from Sweden and Denmark. This is the first study of its kind to include data on twins who were raised apart. This allowed us to better separate genetic and environmental influences.
Researchers found that early estimates were skewed by what scientists call external mortality. This includes deaths from accidents, infectious diseases, and environmental causes. Because the old dataset did not include detailed causes of death, it was not possible to separate these external influences from deaths related to biological aging.
To overcome this challenge, the team created a new analytical approach. They used mathematical models and virtual twin simulations to distinguish between death due to aging and death due to external factors. By filtering out these outside influences, researchers discovered a much stronger genetic signal than previously realized. This finding is consistent with other complex traits in humans and with those observed in animal studies.
The heritability of the risk of dying from dementia by age 80 is about 70%, much higher than the risk of cancer or heart disease.
Aging research and its impact on medicine
These results could change the way scientists think about aging and longevity. If genetics plays a larger role than assumed, this strengthens the case for searching for specific genes that influence longevity.
“For many years, human longevity was thought to be determined almost entirely by non-genetic factors, leading to considerable skepticism about the role of genetics in aging and the feasibility of identifying genetic determinants of longevity,” Shenhar says. “In contrast, as we have shown, high heritability provides an incentive to search for genetic variants that extend lifespan in order to understand and possibly therapeutically address the biology of aging.”
Research support and funding
Professor Uli Aron’s research is supported by the Sagol Longevity Research Institute. Nell Family Artificial Intelligence Research Institute. Moros Integrative Cancer Center. David and Ferra Chappelle Family Genetic Disease Research Center. Zuckerman STEM Leadership Program. and the Rising Tide Foundation.
Professor Aron is the current incumbent of the Abish Frenkel Professorship.
