A person’s genes play a far greater role in likely lifespan than previously thought, according to a major new study published Thursday in the journal Science.
Using data from human twin studies, an international team of researchers arrived at the conclusion that the genetic contribution to how long we’re likely to live is as high as 55%.
This new finding is strikingly higher than previous estimates, which have calculated the role of genetics in lifespan could range from 6% to 33%. It’s likely to intrigue — and perhaps disappoint — the fast-growing community of longevity influencers and self-described biohackers touting longer lives through supplements and customized drug regimens.
The study authors said they arrived at this very different figure by separating out what they termed extrinsic mortality (defined as deaths from external factors such as accidents, homicides, environmental hazards and infectious diseases) and intrinsic mortality (deaths caused by internal biological factors such as age-related diseases, genetic mutations and the general decline of health with age).
Through treating these two categories of death separately, the researchers said they were able to get a far more accurate estimate of the relationship between genetics and lifespan. It also matches with findings regarding the role of genes in other key physiological traits: Height, body fat distribution and muscle build are all thought to be at least 50% heritable.
“The number that we got is not out of nowhere,” said lead study author Ben Shenhar, who researches the physics of aging at the Weizmann Institute of Science in Rehovot, Israel. “If you look at twin studies on pretty much anything in humans, you get this 50%. If you look at the heritability of age of onset at menopause, which is an age-related decline, that is also around 50%.”
Morten Scheibye-Knudsen, an associate professor in the department of cellular and molecular medicine at the University of Copenhagen, described the new approach as a means of “eliminating the outside noise” to unmask the underlying biology of aging. Scheibye-Knudsen, who wrote an editorial published alongside the study, said that through looking at other species, it’s already clear that genes play a significant role in determining lifespan.
“We live [a maximum of] 120 years, and a yeast cell lives 13 days, and bowhead whales live 200 years,” he said. “So we already know our genes have set a limit to our lifespan, as it is now. I think people should have thought a little bit more about that because it cannot only be our behavior.”
Eric Verdin, president and chief executive of the Buck Institute for Research on Aging in California, who was not involved in the study, cautioned that the novel approach the researchers used may not be so clear-cut. Susceptibility to illness and death from infections such as Covid or flu could arguably be considered as intrinsic mortality as such vulnerability is at least partially genetic.
“We know that your genes play an enormous role in how you respond to infection,” said Verdin, who suggested that tweaking the analysis might slightly lower the apparent genetic contribution to lifespan.
Shenhar said that the researchers had considered this and re-ran their analysis, this time accounting for the fact that vulnerability to infections and falls rises as we get older. The findings still revealed that genetic makeup contributes to around 50% of life expectancy.
Shenhar said that the findings underscored the importance of continuing to search for key genes that confer longevity, pointing to other studies that have shown that centenarians appear to carry a lower risk of chronic diseases compared with the average person.
“It’s clear that these people are not just clawing their way to 100,” he said. “No, they have protective genes that protect against the harms of age.”
Verdin said the new study confirmed previous research showing that protective genes appeared to play a particularly crucial role in protecting some people against cardiovascular disease. However, so far only a handful of genetic variants associated with longevity have been discovered, notably versions of the FOXO3, APOE and SIRT6 genes.
“The search has not been very fruitful,” he said. “There are multiple genes that have been shown to be associated with aging, but if you study many centenarians, you don’t find these genes in all of them.”
Verdin continued: “To me this indicates that it comes down to multiple genes interacting with each other, and the key question is identifying which pairs or triplets [of gene variants] which yield longevity. One important step in trying to do this is to sequence the genomes of as many centenarians as possible.”
Shenhar agreed that the secret to a long life is likely to be dictated by multiple genes working in tandem, not one single gene “to rule them all.”
Still, while genetics may play a larger role in lifespan than previously thought, a healthy lifestyle can’t be discounted.
“The depressing thing about this is that it makes people be fatalistic,” Verdin said. “‘It doesn’t matter what I do. Why should I try to live better and not drink and do sport if it’s determined by genes basically?’”
Shenhar said he hopes this isn’t the main takeaway. If genetics dictate 55% of our life expectancy, that means lifestyle still makes up the remaining 45%, a not insignificant proportion.
“The message of our paper is not that lifestyle, exercise and diet are not important,” he said. “That is not our message, not at all. Even if your genetics gives you a particular potential or range for what your natural lifespan would be, depending on lifestyle, that might shift slightly one way or another. So it’s still important.”