The secret to long life? It could be in the genes after all, say scientists | Genetics

Some people who live to be very old attribute it to a night full of whiskey, others to avoiding trouble. Now scientists think they may have discovered a key secret to long life: simply put, genetics.

Writing in the journal Science, the researchers described how previous studies that attempted to analyze the genetic component of human lifespan failed to take into account that some lives are cut short by accidents, murder, infectious diseases, or other factors occurring outside the body. This “extrinsic mortality” increases with age, as people often become more fragile.

Professor Uri Alon and colleagues at the Weizmann Institute of Science in Israel say the true genetic contribution to variation in human lifespan has been obscured.

The team looked at “heritability,” the proportion of change in a trait such as height, weight or lifespan within a population that can be attributed to genetics rather than environmental factors. Previous studies of human lifespan have found a wide range of values ​​– heritability ranging from 6% of variation to 33%.

But Alon, a co-author of the study, and his colleagues said those numbers were underestimates. “I hope this will inspire researchers to undertake an in-depth search for genes that impact lifespan,” Alon said. “These genes will tell us the mechanisms that govern our internal clocks.

“These may one day be turned into a therapy to slow the rate of aging and thus slow all age-related diseases in one fell swoop.” »

The team created a mathematical model that takes into account extrinsic mortality and the impact of biological aging, and calibrated it using lifespan correlations from historical datasets of thousands of twin pairs in Denmark and Sweden.

They removed the impact of extrinsic mortality to reveal the signal of biological aging, caused by genetics. The results suggest that about 50% of the variation in human lifespan is due to genetics – a figure that the researchers say is comparable to that observed in wild mice in the laboratory.

They say the remaining 50 percent of the variation in human lifespan is likely explained by factors such as random biological effects and environmental influences.

“This is where we expect to find all the usual suspects: lifestyle, diet, exercise, social relationships, environment and more,” said Ben Shenhar, co-author of the research, adding that lifestyle and environment are likely to become more important as we age.

The team tested their results using data from a US study of siblings of centenarians and found a heritability of lifespan of around 50%.

Further testing using another Swedish dataset found that as extrinsic mortality declined from the early 20th century onwards – likely due to factors such as improved public health – the estimated genetic contribution to lifespan increased, supporting the idea that extrinsic mortality was a key factor in heritability. The team also found that the heritability of lifespan varied depending on the cause of death, such as cancer or dementia, and age.

Shenhar added that daily experience showed that genetics played an important role in longevity. “About 20% of centenarians, for example, reach age 100 without any serious, debilitating illnesses,” he said, adding that this could suggest their genes had a protective effect. “Studies have been done to identify these protective genes, and many have been discovered, but there are surely many more to be discovered,” he said.

Although the new study does not take into account the influence that genes may have on the immune system, Professor Richard Faragher of the University of Brighton said the research suggested that humans did not appear to be an exception when it came to the heritability of lifespan.

“And that’s useful because it means that humans are a lot like a species in which we study aging, [and] gives you some confidence that interventions that will work in mice will translate to humans,” he said.