Longevity may be 50% heritable, research suggests

About 50% of a person’s lifespan is determined by genetics, a new study suggests, more than doubling previous estimates of the heritability of longevity.

The new study, published in the journal Science on January 29, used a carefully designed mathematical model to reach this conclusion. Using this model, the research team was able to account for external causes of death, such as accidents and infections, allowing them to exclude these environmental factors from their heritability estimates.

The heritability of various human traits is typically determined using twin studies. This allows scientists to compare individuals who share nearly 100% or 50% of their DNA. Identical twins, or “identical” twins, share nearly all of their DNA, while fraternal twins, or “fraternal” twins, share only 50%.

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The researchers looked at the correlation between lifespan and genetic traits in individual twin sets, and then compared how well those metrics matched across many twin sets. “If a trait is highly genetically determined, the correlation between identical twins will be much higher than the correlation between dizygotic twins,” said study co-author Joris Dielen, a geneticist at Leiden University in the Netherlands.

Previous estimates from such studies have suggested that the heritability of human lifespan is only between 6% and 25%, suggesting that genetics has a limited influence on human lifespan. These estimates are significantly lower than estimates of the heritability of other complex human traits, such as mental disorders, and of lifespan observed in other mammals, both of which are typically around 50%.

But observations of long-lived families and genetic risks associated with age-related diseases such as heart disease suggest to Dielen and colleagues that there is likely a much larger genetic contribution to longevity than scientists once thought.

Another way to look at lifespan

The challenge is separating factors that have a strong genetic component to death, such as the risk of age-related diseases and the rate of physical decline, from external factors such as accidents or infections. Dielen pointed out that the distinction between these genetic and external factors is not always clear-cut. But in the case of infectious diseases, for example, they focused on diseases that were generally very treatable, such as scarlet fever.

“Previously, when studying lifespan and predictors, we tended to use all-cause mortality, where we only looked at what age people died and didn’t really consider what the cause was. The cause of death was often missing. [from those records]” said Luke Pilling, a geneticist at the University of Exeter in the UK who was not involved in the study.

Dielen’s team, which included geneticists, doctors and statisticians, designed a model that could mathematically account for these extrinsic factors, even when the cause of death was unknown. The researchers fed data from twin cohorts in Sweden, Denmark, and the United States into the model and showed that each had estimated lifespan heritability of about 50%. The dataset collectively included people born between 1870 and 1935.

“They also looked at this study of Swedish twins born between 1900 and 1935 and were able to do a very interesting analysis stratified by decade,” Pilling added. “Twins born in 1900 experienced very different exposures to infectious diseases than twins born in the 1930s, so their extrinsic mortality rate decreased over that period.”

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Classical estimates of the heritability of lifespan are likely to show that heritability increases over that period of time as genetic factors begin to dominate the calculation. This would support the idea that environmental causes of death were influencing previous estimates. In contrast, the new model provides consistent heritability estimates regardless of these external factors.

However, like all models, the new approach has limitations. “The best-case scenario is that you know the actual cause of death, and you have a cohort where you can directly classify it as intrinsic or extrinsic, and you don’t have to model it,” Dielen says. “But that data just doesn’t exist.”

Furthermore, due to the lack of similar data from other regions, the model has so far been primarily tested on people of Northern European descent.

“That’s a big question,” Dielen said. “Is this heritability unique to the Nordic countries, or is it similar in other parts of the world?”

Modern record-keeping may help scientists determine the answer in the future. But for now, what do these results mean for medicine?

Professor Pilling said understanding the genetic markers that influence how long people live, and how long they can stay healthy during that lifespan, will have important implications for the future of geriatric care, especially as more and more countries grapple with aging populations.

“If we can understand the biological mechanisms by which people live longer and healthier, perhaps we can design interventions that promote those pathways and promote healthspan (the period of life spent in good health),” Pilling said. “I would definitely like to use this for research.”

Importantly, however, Dielen says, a 50% heritability estimate neither guarantees a long life nor dooms it to a short life.

“What this shows us is that humans have a tendency to live longer in our genes, and the rest is determined by what we do and where we live,” he said. “The environment remains extremely important and people should strive to optimize their lifestyles as much as possible.”