Lifespan may be 50% heritable, study suggests

Around 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 research, published Jan. 29 in the journal Science, used a carefully designed mathematical model to reach this conclusion. With the model, the team behind the work could account for external causes of death, such as accidents or infections, eliminating these environmental factors from their heritability estimates.

The heritability of different human traits is usually determined using twin studies, which enable scientists to compare individuals who share either nearly 100% or 50% of their DNA. Identical, or "monozygotic," twins share nearly all of their DNA, while fraternal, or "dizygotic," twins share only 50%.

The researchers looked at the correlation of lifespan and genetics in individual sets of twins, and then compared how well those metrics matched across many sets of twins. "If a trait is very genetically determined, then the correlation in the monozygotic twins will be much higher than the correlation in the dizygotic twins," said study co-author Joris Deelen, a geneticist at Leiden University in the Netherlands.

Previous estimates from such studies have placed the heritability of human lifespan between just 6% and 25%, which suggested genetics have a limited influence on how long people live. Those estimates are substantially lower than those for other complex human traits, such as psychiatric disorders, or the heritability of life span observed in other mammals, which are both typically placed at around 50%.

However, observations of long-lived families and the genetic risk associated with age-related diseases, such as heart disease, suggested to Deelen and colleagues that longevity likely has a far larger genetic contribution than scientists once thought.

A different way of looking at lifespan

The difficulty lies in separating drivers of death with strong genetic components — such as the risk of age-related diseases or the speed of physical decline — from external factors, such as accidents and infections. Deelen did note that the divide between these genetic and external factors is not always clear cut; but in the case of infections, for instance, they focused on diseases that are generally very treatable, such as scarlet fever.

"Previously, when we studied lifespan and predictors, we tended to use all-cause mortality, where we're just looking at what age people died and not really considering what the causes are — cause of death is often missing [from those records]," said Luke Pilling, a geneticist at the University of Exeter in the U.K. who wasn't involved in the work.

Deelen's team — which included geneticists, physicians and statisticians — designed a model to mathematically account for these extrinsic contributors, even for cases when the causes of death were not available. The team fed data from twin cohorts in Sweden, Denmark and the U.S. into the model, and each returned an estimated lifespan heritability of around 50%. The datasets collectively included people born between 1870 and 1935.

"They also looked at this study of Swedish twins born between 1900 and 1935, and that allowed them to do a really interesting analysis, stratified by decade," Pilling added. "Because the twins born in 1900 experienced a very different exposure to infection to the twins born in the 1930s, extrinsic mortality was decreasing over that period."

Classical estimates of lifespan heritability would likely show an increase in heritability over that time frame, as genetic factors began to dominate the calculations. That would support the idea that environmental causes of death had influenced previous estimates. In contrast, the new model gives a consistent estimate for heritability, independent of those external factors.

Like all models, though, the new approach has limitations. "The best scenario would be to have a cohort where you know the actual cause of death and can classify it directly as intrinsic or extrinsic so you don't need to model it in," Deelen said. "But that data just doesn't exist."

In addition, the model has so far been tested primarily on people of Northern European descent, owing to a similar lack of data from elsewhere.

"It's a big question," Deelen said. "Is this heritability something specific for Nordic countries, or is it similar in other parts of the world?"

Modern recordkeeping may enable scientists to determine the answer in the future. But for now, what could these results mean for medicine?

Understanding the genetic markers that influence how long people live — and how long they remain healthy during that lifespan — has important consequences for the future of geriatric medicine, Pilling said, particularly as more and more countries deal with aging populations.

"If we understand the biological mechanisms that cause people to live longer and healthier, we can perhaps design interventions to promote those pathways and to promote health span — the period of life spent in good health," Pilling said. "I will certainly be using this in my research."

Crucially, though, the 50% heritability estimate neither guarantees you a long life or dooms you to a short one, Deelen said.

"What it shows is that you have a certain propensity to become long-lived which is in your genes, and the rest is based on what you do and where you live," he clarified. "Environment is still super important, and people should try to optimize their lifestyle as much as they can."