A person’s genes play a much larger role in lifespan than thought

A person’s genes play a much larger role in likely lifespan than previously thought, according to a major new study published Thursday in the journal Science.

Using data from studies of human twins, an international team of researchers has concluded that the genetic contribution to the likely length of our lives reaches 55%.

This new finding is surprisingly higher than previous estimates, which estimated that the role of genetics in lifespan could range from 6% to 33%. This is likely to intrigue – and perhaps disappoint – the growing community of longevity influencers and self-proclaimed biohackers touting longer lives through personalized supplements and drug regimens.

The study authors said they arrived at this very different figure by separating what they call extrinsic mortality (defined as deaths due to 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 general decline in health with age).

By treating these two categories of deaths separately, the researchers said they were able to get a much more precise estimate of the relationship between genetics and lifespan. This is also consistent with findings regarding the role of genes in other key physiological traits: height, body fat distribution, and muscle building are all thought to be at least 50% hereditary.

“The number we got didn’t come out of nowhere,” said the study’s lead author, Ben Shenhar, who researches the physics of aging at the Weizmann Institute of Science in Rehovot, Israel. “If you look at twin studies of just about anything in humans, you get that 50%. If you look at the heritability of age of onset at menopause, which is an age-related decline, it’s also about 50%.”

Morten Scheibye-Knudsen, associate professor at the University of Copenhagen’s department of cellular and molecular medicine, described the new approach as a way to “eliminate outside noise” to unmask the underlying biology of aging. Scheibye-Knudsen, who wrote an editorial published alongside the study, said that by looking at other species, it is already clear that genes play an important role in determining lifespan.

“We live [a maximum of] “We already know that our genes have set a limit to our lifespan, as is the case today. I think people should have thought about it a little more, because it can’t just be due to our behavior.

Eric Verdin, president and CEO of the Buck Institute for Research on Aging in California, who was not involved in the study, cautioned that the novel approach used by researchers may not be as clear. Susceptibility to illness and death from infections such as Covid or influenza could arguably be considered intrinsic mortality, to the extent that this vulnerability is at least partially genetic.

“We know that your genes play a huge role in how you respond to infection,” said Verdin, who suggested that changing the analysis could slightly reduce the apparent genetic contribution to lifespan.

Shenhar said the researchers thought about this and reran their analysis, this time taking into account that vulnerability to infections and falls increases as we age. The results nevertheless reveal that genetic makeup contributes to approximately 50% of life expectancy.

Shenhar said the findings highlighted the importance of continuing to search for key genes that confer longevity, pointing to other studies that have shown that centenarians appear to have a lower risk of chronic diseases compared to the average person.

“It’s clear that these people aren’t just making their way to 100 years,” he said. “No, they have protective genes that protect against the harms of aging.”

Verdin said the new study confirmed previous research showing that protective genes appear to play a particularly crucial role in protecting some people from cardiovascular disease. However, so far only a handful of genetic variants associated with longevity have been discovered, including versions of the FOXO3, APOE and SIRT6 genes.

“The search hasn’t been very fruitful,” he said. “Several genes 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 these are several genes that interact with each other, and the key question is to identify which pairs or which triplets [of gene variants] which ensure longevity. An important step in achieving this is to sequence the genomes of as many centenarians as possible.

Shenhar agrees that the secret to a long life will likely be dictated by multiple genes working in tandem, not a single gene “to rule them all.”

Yet even though genetics may play a larger role in lifespan than previously thought, a healthy lifestyle cannot be ruled out.

“The depressing thing about this situation is that it makes people fatalistic,” Verdin said. “‘It doesn’t matter what I do. Why should I try to live better and not drink and exercise if it’s fundamentally determined by genes?'”

Shenhar said he hopes that’s not the main takeaway. If genetics determines 55% of our life expectancy, this means that lifestyle still represents the remaining 45%, a significant proportion.

“The message of our article is not that lifestyle, exercise and diet are not important,” he said. “That’s not our message at all. Even if your genetics give you a particular potential or range for what your natural lifespan would be, depending on your lifestyle, it may slightly change one way or another. So it’s still important.”