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Some people who live to a great age put it down to an evening tot of whisky, others to staying out of trouble. Now scientists think they may have unlocked a key secret to long life – quite simply, genetics.
Writing in the journal Science, the researchers described how previous studies that had attempted to unpick the genetic component of human lifespan had not taken into account that some lives were cut short by accidents, murders, infectious diseases or other factors arising outside the body. Such “extrinsic mortality” increases with age, as people often become more frail.
Prof Uri Alon and colleagues at the Weizmann Institute of Science in Israel say the true genetic contribution to the variation in human lifespan has been masked.
The team looked at “heritability”, the proportion of change in a characteristic such as height, body weight or lifespan within a population that can be attributed to genetics rather than environmental factors. Previous studies for human lifespan have thrown up a wide range of values – with heritability ranging from 6% of the variation to 33%.
But Alon, who co-authored the research, and his colleagues said such figures were underestimates. “I hope this will inspire researchers to make a deep search for the genes that impact lifespan,” Alon said. “These genes will tell us the mechanisms that govern our internal clocks.
“These can one day be turned into therapy to slow down the rate of ageing and in that way slow down all age-related disease at once.”
The team created a mathematical model that takes into account extrinsic mortality and the impact of biological ageing, and calibrated it using correlations of lifespan from historical datasets of thousands of pairs of twins in Denmark and Sweden.
They removed the impact of extrinsic mortality to reveal the signal from biological ageing, which is caused by genetics. The results suggest about 50% of the variation in human lifespan is due to genetics – a figure the researchers said was on a par with that seen in wild mice in the laboratory.
The other 50% of variation in human lifespan, they said, was probably explained by factors such as random biological effects and environmental influences.
“That’s where we would expect to find all the usual suspects – lifestyle, diet, exercise, social relations, environment, and more,” said Ben Shenhar, who co-authored the research, adding that lifestyle and environment were 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 about 50%.
Further testing using another Swedish dataset revealed that as extrinsic mortality fell from the start of the 20th century – likely due to factors such as improvements in public health – the estimated genetic contribution to lifespan rose, supporting the idea that extrinsic mortality was a key factor when looking at heritability. The team also found the heritability of lifespan varied depending on the cause of death, such as cancer or dementia, and age.
Shenhar added that day-to-day experience showed genetics played an important role in longevity. “Around 20% of centenarians, for example, reach age 100 without any serious debilitating illnesses,” he said, adding that could suggest their genes had a protective effect. “Studies have been conducted to identify these protective genes, and many have been found, but surely there are many still left to discover,” he said.
While the new study does not take into account the influence that genes can have on the immune system, Prof Richard Faragher of the University of Brighton said the research suggested humans did not seem to be an outlier when it came to the heritability of lifespan.
“And that’s useful because it means humans look quite like a species that we study ageing in, [and] gives you a certain amount of confidence that interventions that will work in mice will carry over into humans,” he said.
