We may have less control over how long we live than previously thought
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Uri Alon has long been intrigued by a classic statistic: Longevity, it was thought, was about 20 percent in our genes.
“It makes you think about what the rest of the 80 percent is: Is it lifestyle? Why should we study genes for lifespan if it’s not that important? That bothered me a little,” said Alon, a physicist turned systems biologist at the Weizmann Institute of Science in Israel.
Alon uses mathematical models to understand complex biological problems, and he and his colleagues built one to reexamine the factors that define the contours of human lifespan in a scientific study published earlier this year.
The original studies used to estimate inherited lifespan were studies of Scandinavian twins dating from the late 19th century.
At that time, “extrinsic” mortality—deaths not related to the deterioration of aging, such as accidents, violence, or deaths from infections, now rare due to better diets, therapies, and hygiene—was high.
His team examined a database of Swedish twins born later, between 1900 and 1935, and found that these extrinsic deaths masked the hereditary component of lifespan. When they applied their model, designed to eliminate extrinsic deaths, to databases of Scandinavian twins and siblings of people who had lived at least 100 years, the heritability of lifespan increased significantly – to about half.
It’s not that the old studies were wrong: They focused on longevity in a different era, a generation born between 1870 and 1900. “In those days, people were dying of pneumonia and tuberculosis, and few people reached their 40s,” Alon said. “In this situation, it doesn’t matter how long your parents live? Genes don’t stand a chance.”
Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine, who was not involved in the study, pointed to his own family history. His grandfather had a heart attack and died at the age of 68. His father had a heart attack at the same age, but underwent triple bypass surgery and lived to be 84.
“Do father and son live the same number of years? No, because if you look at fathers and sons, what happens in between is the advancement of medicine,” Barzilai said.
If half the lifespan is inherited, what does that mean?
With hindsight, it may be obvious that genes play a major role in determining lifespan.
“As humans, we live very different lives than other organisms, and the difference between you and me, a mouse or a bowhead whale, or a bristlecone pine that lives 5,000 years, or the yeast in dough that lives 13 days, the real difference is in the genes,” said Morten Scheibye-Knudsen, an associate professor specializing in aging research at the University of Copenhagen, who did not participate in the study.
But because previous studies had suggested that human lifespan was only 10 to 30 percent hereditary, “this sort of gave us some freedom to imagine that we could live to be very old, and that we had control and were masters of our own aging,” Scheibye-Knudsen added. The new study reignites the debate, showing that genetics and environment both matter.
Thomas Perls, a longevity researcher at Boston University and founding director of the New England Centenarian Study, agrees that genetics play a major role in lifespan, but that it depends on what age you’re talking about.
At extreme ages – in people who live to 105 or even 110 – genetics play a major role in lifespan. But Perls points to a 2018 study in the journal Circulation suggesting that even without winning the genetic lottery, the average person can probably reach about 88 years old as a man and 93 years old as a woman. It depends on adopting good health-related behaviors. He notes that socio-economic benefits also contribute: access to health care, education and healthy food.
“I think the average human being and the average genetic makeup provides resilience and resistance to aging, better than people thought in the past,” Perls said.
Alon sees this as a “genetic set point.” The age of our parents and grandparents at the time of their death has some effect on the likelihood of our longevity. Healthy habits can add years, but the benefits are less pronounced than bad habits, which can reduce lifespan by decades.
How should we live?
Don’t give up!
For scientists looking for genes linked to longevity, the new evidence highlights the urgency of investigating the biological mechanisms behind very long lifespans. A deeper understanding of the hundreds of tiny variations in genes that influence lifespan could provide targets for drugs that could influence aging.
But Alon still eats salad and swims. While several longevity scientists gave different figures for the number of years a healthy life could add to an individual’s life trajectory, from five to 20, they all agreed there was a game in the system. What is clearer is that unhealthy behaviors can significantly reduce it.
“What is your starting point? You actually don’t know. We have no way of measuring that,” Scheibye-Knudsen said. “So, unfortunately – or fortunately, depending on how you look at it – that means no smoking, drinking in moderation and eating your vegetables.”
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