It’s gotta be the genes: Israeli study finds genetics play key role in human longevity

WASHINGTON (Reuters) — Many factors influence how long you live, such as diet, exercise, smoking, drinking, environment and other variables. It also helps not to get hit by a dump truck. But what about your genes? That has been a contentious question for decades.

A new study points to a larger role for genetics than previous research had indicated, estimating the contribution of genes to determining human lifespan at about 50 percent. That is roughly double what prior research concluded, and it mirrors the findings of lifespan studies in laboratory animals.

“Lifespan is undoubtedly shaped by many factors, including lifestyle, genes and, importantly, randomness — take for example genetically identical organisms raised in similar environments that die at different times,” said Ben Shenhar, a doctoral student in physics at the Weizmann Institute of Science in Israel and lead author of the peer-reviewed study published on Thursday in the journal Science.

“In our work, we tried to give a handle on the amount of variance between different people that can be attributed to genetics. Our study tried to partition the longevity factors into genetics and ‘everything else.’ The ‘everything else’ is around 50% of the pile.”

The researchers sought to account for a confounding factor in previous studies that used Swedish and Danish twins, most dating to the 19th century. Those twin studies did not account for deaths caused by violence, accidents, infectious diseases and other factors originating outside the body — called extrinsic mortality — that the authors of the new study said skewed earlier findings about longevity’s genetic component.

The cause of death was absent in the historical data, which provided merely the age at death. So if one twin died at age 90 of natural causes and the other twin died at age 30, not of natural causes but due to an infectious disease such as typhus or cholera, data lacking the cause of death could provide a misleading impression about the role of heredity in lifespan.

The new study employed a mathematical formula to account for extrinsic mortality among twins. Shenhar said extrinsic mortality at the time when the studied twins lived, before the era of antibiotics, was 10 times higher than today, primarily because of infectious diseases that are now readily curable.

The researchers then validated the prediction that extrinsic deaths mask heritability by using previously unanalyzed and more recent data from Sweden that included twins raised together and twins raised apart. This analysis indeed found that as extrinsic mortality falls, heritability rises.

“Identical twins raised apart share their genes, but not their environment. This helps tease apart genetics from the environment, nature from nurture,” Weizmann Institute systems biologist and study senior author Uri Alon said.

Fraternal twins are also valuable in such research because they share about half their genetic makeup.

“Previous twin studies used statistical methods that work well for other traits — height, blood pressure, personality traits, etc. These traits are not affected by extrinsic mortality,” Alon said.

“But mean lifespan is the one special trait that is strongly affected by extrinsic mortality. Since cause of death was not recorded for the classical twin studies, it was not corrected for,” Alon said.

The conclusions may have implications for research into aging.

“Low heritability estimates may have discouraged funding and research into the genetics of aging, suggesting it was largely random or environmental. Our work validates the search for genetic factors of longevity, showing that the genetic signal is strong but was previously hidden by ‘noise’ in the data,” Shenhar said.

Genes impact lifespan in both directions. On one hand, there are debilitating genetic defects that can cause disease and shorten longevity. On the other hand, there are genes that have been identified that appear to offer benefits for longevity.

“Many centenarians reach age 100 without any serious medical conditions,” Shenhar said. “It’s clear that these people have protective genes which guard against developing diseases that naturally occur with age. Some of these genes have been identified, although, like most complex traits, longevity is likely impacted by hundreds if not thousands of genes.”