Genes could shape our lifespan, they thought more than once

How long you live may depend more on your genes than scientists thought.

Once you have ruled out life-shortening events – such as infections and injuries – genetics account for about half of the factors that determine human lifespanreport the researchers in January 29 Science. The findings challenge the commonly held notion that lifespan is primarily determined by lifestyle and environmental factors.

It is important to determine the extent to which human lifespan results from genes to understand aging more generally. “If we can understand why some people can reach 110 years old by smoking and drinking their entire lives, then perhaps in the future we can also translate this into interventions or medicine,” says biophysicist Ben Shenhar of the Weizmann Institute of Science in Rehovot, Israel.

So far, many studies of human populations have estimated that the heritability – the extent to which genetic differences are responsible for biological variation – of lifespan is about 20 to 25 percent. Some estimates are as low as 6 percent. This has led to the prevailing view that the length of life is determined primarily by external factors. In recent years, such studies have led to skepticism about the importance of the genetic study of aging and longevity in general.

Shenhar and colleagues did not set out to determine the heritability of lifespan. The researchers had studied how aging varies in human populations using mathematical modeling. One day, Shenhar was tinkering with some inputs to a model and noticed that removing extrinsic mortality – deaths caused by events outside the body, such as environmental riskshomicides or accidents – increased the theoretical heritability of lifespan.

Wondering if this was a real phenomenon, the researchers dug deeper.

The team compiled mortality data from Swedish, Danish and American databases as well as datasets from three different lifespan studies in a collection of Danish and Swedish twins and a study of siblings of American centenarians. Because this historical data lacks information on the cause of death, the team had to mathematically estimate and separate the impact of deaths from external factors in the data sets. The overall mortality rate generally increases with the years, but previous research has shown that any population experiences a mortality plateau between the ages of 20 and 40. This is due to a decline in extrinsic mortality during these years. Shenhar and his team used the value of this plateau to calculate and separate extrinsic mortality. From there, they could calculate the heritability of lifespan with and without these added external factors.

This helped the team answer a hypothetical question: “Let’s say I could raise humans in a lab like I raise mice, and I feed everyone the same food, and I make sure they’re all doing the same activity, so I control their environment,” he said. “How much do their genes impact their lifespan? »

When the team applied their model to both datasets, the heritability of lifespan was consistently high, at around 55%, double that found in many previous studies. The results represent a turning point in our understanding of lifespan, says Shenhar.

“Most human physiological traits from twin studies are about 50 percent heritable,” he says. “We’re bringing lifespan – which we thought was very different – ​​back onto the same playing field with the rest of the traits.”

This new calculation of lifespan heritability also more closely resembles what scientists have estimated in laboratory animals such as mice and flies.

Biostatistician Paola Sebastiani, who was not involved in the study, notes that the new results are closer to those of her and her colleagues. had estimated the heritability of extreme longevity – living more than 100 years – in humans. In the future, removing extrinsic deaths from studies of genetic factors that impact lifespan could increase the discovery power of these studies, says Sebastiani, of the Tufts Clinical and Translational Science Institute in Boston.

Shenhar next wants to target the environmental side of the lifespan equation. “How much of it is just this kind of inherent chance,” he asks, “and how much of it is lifestyle?” »