Laura Oliveira fell in love with swimming at 70. She won her first competition three decades later. Longevity runs in her family. Her aunt Geny lived to 110. Her two sisters thrived and were mentally sharp beyond a century. They came from humble backgrounds, didn’t stick to a healthy diet—many loved sweets and fats—and lacked access to preventative screening or medical care. Extreme longevity seems to have been built into their genes.
Scientists have long sought to tease apart the factors that influence a person’s lifespan. The general consensus has been that genetics play a small role; lifestyle and environmental factors are the main determinants.
A new study examining two cohorts of twins is now challenging that view. After removing infections, injuries, and other factors that cut a life short, genetics account for roughly 55 percent of the variation in lifespan, far greater than previous estimates of 10 to 25 percent.
“The genetic contribution to human longevity is greater than previously thought,” wrote Daniela Bakula and Morten Scheibye-Knudsen at the University of Copenhagen, who were not involved in the study.
Dissecting the impact of outside factors versus genetics on lifespan isn’t just academic curiosity. It lends insight into what contributes to a long life, which bolsters the quest for genes related to healthy aging and strategies to combat age-related diseases.
“If we can understand why there are some people who can make it to 110 while smoking and drinking all their life, then maybe, down the road, we can also translate that to interventions or to medicine,” study author Ben Shenhar of the Weizmann Institute of Science told ScienceNews.
Genetic Mystery
Eat well, work out, don’t smoke, and drink very moderately or not at all. These longevity tips are so widespread they’ve gone from medical advice to societal wisdom. Focusing on lifestyle factors makes sense. You can readily form healthy habits and potentially alter your genetic destiny, if just by a smidge, and genes hardly seem to influence longevity.
Previous studies in multiple populations estimated the heritability of lifespan was roughly 25 percent at most. More recent work found even less genetic influence. The results poured cold water on efforts to uncover genes related to longevity, with some doubting their impact even if they could be found.
But the small role of genes on human longevity has had researchers scratching their heads. The estimated impact is far lower than in other mammals, such as wild mice, and is an outlier compared to other complex heritable traits in humans—ranging from psychiatric attributes to metabolism and immune system health—which are pegged at an average of roughly 49 percent.
To find out why, the team dug deep into previous lifespan studies and found a potential culprit.
Most studies used data from people born in the 18th and 19th centuries, where accidents, infectious diseases, environmental pollution, and other hazards were often the cause of an early demise. These outside factors likely masked intrinsic, or bodily, influences on longevity—for example, gradual damage to DNA and cellular health—and in turn, heavily underestimated the impact of genes on lifespan.
“Although susceptibility to external hazards can be genetically influenced, mortality in historical human populations was largely dominated by variation in exposure, medical care, and chance,” wrote Bakula and Scheibye-Knudsen.
Twin Effect
The team didn’t set out to examine genetic influences on longevity. They were developing a mathematical model to gauge how aging varies in different populations. But by playing with the model, they realized that removing outside factors could vastly increase lifespan heritability.
To test the theory, they analyzed mortality data from Swedish twins—both identical and fraternal—born between 1900 and 1935. The time period encompassed some environmental extremes, including a deadly flu pandemic, a world war, and economic turmoil but also vast improvements in vaccination, sanitation, and other medical care.
Because identical twins share the same DNA, they’re a valuable resource for teasing apart the impact of nature versus nurture, especially if the twins were raised in different environments. Meanwhile, fraternal twins have roughly 50 percent similar DNA. By comparing lifespan between these two cohorts—with and without external factors added in using a mathematical model—the team teased out the impact of genes on longevity.
To further validate their model, the researchers applied it to another historical database of Danish twins born between 1890 and 1900, a period when deaths were often caused by infectious diseases. After excluding outside factors, results from both cohorts found the influence of genes accounted for roughly 55 percent of variation in lifespan, far higher than previous estimates. They unearthed similar results in a cohort of US siblings of centenarians.
Longevity aside, the analysis also found a curious discrepancy between the chances of inheriting various age-related diseases. Dementia and cardiovascular diseases are far more likely to run in families. Cancer, surprisingly, not so much. This suggests tumors are more driven by random mutations or environmental triggers.
The team emphasizes that the findings don’t mean longevity is completely encoded in your genes. According to their analysis, lifestyle factors could shift life expectancy by roughly five years, a small but not insignificant amount of time to spend with loved ones.
The estimates are hardly cut-and-dried. How genetics influence health and aging is complex. For example, genes that keep chronic inflammation at bay during aging could also increase chances of deadly infection earlier in life.
“Drawing a clear, bright line between intrinsic and extrinsic causes of death is not possible,” Bradley Willcox at the University of Hawaii, who was not involved in the study, told The New York Times. “Many deaths live in a gray zone where biology and environment collide.”
Although some experts remain skeptical, the findings could influence future research. Do genes have a larger impact on extreme longevity compared to average lifespan? If so, which ones and why? How much can lifestyle influence the aging process? According to Boston University’s Thomas Perls, who leads the New England Centenarian Study, the difference in lifespan for someone with only good habits versus no good habits could be more than 10 years.
The team stresses the analysis can’t cover everyone, everywhere, across all time. The current study mainly focused on Scandinavian twin cohorts, who hardly encapsulate the genetic diversity and socioeconomic status of other populations around the globe.
Still, the results suggest that future hunts for longevity-related genes could be made stronger by excluding external factors during analysis, potentially increasing the chances of finding genes that make outsized contributions to living a longer, healthier life.
“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,” said Shenhar in a press release. “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.”
