The length of your life may depend more upon your genes than scientists thought.
Once you remove from consideration events that cut life short — such as infections and injury — genetics account for about half the factors that determine human life span, researchers report in the Jan. 29 Science. The findings challenge the prevalent view that life span is determined mostly by lifestyle and environmental factors.
Determining how much of human life span results from genes is important for understanding aging more generally. “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,” says biophysicist Ben Shenhar of the Weizmann Institute of Science in Rehovot, Israel.
Until now, many studies on human populations have estimated that the heritability — how much genetic differences are responsible for biological variation — of life span is around 20 to 25 percent. Some estimates are as low as 6 percent. This has led to the dominant view that the duration of your life is determined primarily by external factors. In recent years, such studies have led to skepticism toward the importance of the genetic study of aging and longevity overall.
Shenhar and his colleagues didn’t set out to determine the heritability of life span. The researchers had been studying how aging varies in human populations using mathematical modeling. One day, Shenhar was tinkering with some of the inputs of a model and noticed that cutting out extrinsic mortality — deaths caused by events outside the body, such as environmental hazards, homicides or accidents — caused theoretical life span heritability to jump.
Wondering if this was a real phenomenon, the researchers dove deeper.
The team compiled mortality data from Swedish, Danish and U.S. databases along with datasets from three different studies of life span in a collection of Danish and Swedish twins and a study on the siblings of U.S centenarians. Because these historical data lack cause-of-death information, the team had to mathematically estimate and separate the impact of deaths from external factors in the datasets. The overall mortality rate generally rises with advancing years, but previous research showed that any population has a plateau in mortality between the ages of 20 and 40. This is caused by a dip in extrinsic mortality during those years. Shenhar and his team used the value of that plateau to calculate and separate out extrinsic mortality. From there, they could calculate the heritability of life span with and without those external factors added in.
This helped the team answer a hypothetical question: “Let’s say I could raise human beings in a lab like I raise mice, and I feed everyone the same food, and I make sure they all exercise the same, so I control their environments,” he says. “How much do their genes impact their life span?”
When the team applied their model to the twin datasets, the heritability of life span was consistently high, at around 55 percent — twice that found in many previous studies. The findings represent a pivot in our understanding of life span, Shenhar says.
“Most human physiological traits from twin studies are around 50 percent heritable,” he says. “We’re bringing back life span — which was thought to be very different — into the same playing field with the rest of the traits.”
This new calculation of life span heritability also more closely resembles what scientists have estimated in laboratory animals such as mice and flies.
Biostatistician Paola Sebastiani, who was not involved with the study, notes that the new findings are closer to what she and her colleagues had estimated for the heritability of extreme longevity — living over 100 years — in humans. In the future, removing extrinsic deaths in studies on the genetic factors that impact life span may increase the discovery power of these studies, says Sebastiani, of Tufts Clinical and Translational Science Institute in Boston.
Shenhar is interested in targeting the environmental side of the life span equation next. “How much of that is just this kind of inherent randomness,” he asks, “and how much of that is lifestyle?”
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