Uri Alon was long puzzled by a textbook statistic: longevity, the thinking went, was about 20 percent in our genes.
“That makes you think what’s the rest of the 80 percent: Is it the lifestyle? Why should we study genes for lifespan if it’s not that important? It kind of bothered me,” said Alon, a physicist-turned-systems biologist at the Weizmann Institute of Science in Israel.
Alon uses mathematical models to understand complicated biological problems, and he and his colleagues built one to reexamine the factors that define the contours of human lifespan in a Science study published earlier this year.
The original studies that were used to estimate how much of lifespan was inherited were studies of Scandinavian twins from the tail-end of the 19th century.
During that era, “extrinsic” mortality was high — deaths that aren’t related to the deterioration of aging, such as accidents, violence or deaths from infections that are now uncommon because of better nutrition, therapies and hygiene.
His team examined a database of Swedish twins born later, between 1900 and 1935, and found that these extrinsic deaths were masking the inherited component of lifespan. When they applied their model, designed to remove extrinsic deaths, to databases of Scandinavian twins and the siblings of centenarians who lived to at least 100, the heritability of lifespan markedly increased — to about half.
It isn’t that the old studies were wrong: They were focused on longevity in a different era — a generation born between 1870 and 1900. “At that time, people died of pneumonia and tuberculosis and not a lot of people made it to their 40s,” Alon said. “In that situation, who cares how long your parents lived? Genes don’t have 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 got a heart attack at the same age, but had a triple bypass surgery and lived to 84.
“Do the father and the son live the same amount of years? No, because if you look at fathers and sons, what happens in between is progress in medicine,” Barzilai said.
If half of lifespan is inherited, what does that mean?
In hindsight, it is perhaps 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 the genes,” said Morten Scheibye-Knudsen, an associate professor focused on aging research at the University of Copenhagen who was not involved in the study.
But because previous studies had suggested human lifespan was only 10 to 30 percent heritable, “that in some way gave us some liberty in imagining we could live to become very old, and we had control and were masters of our own aging,” Scheibye-Knudsen added. The new study resets the discussion, showing that both genetics and environment are important.
Thomas Perls, a longevity researcher at Boston University and the 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 are talking about.
At the very extremes of old age — 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 that suggests that even without winning the genetic lottery, an average person can probably get to about 88 years old as a man, and 93 years old as a woman. That depends on embracing good health-related behaviors. He also notes that socioeconomic advantages contribute — access to health care, education, healthy food.
“I think that the average human being and the average genetic makeup provide resilience and resistance to aging, better than people have thought in the past,” Perls said.
Alon thinks of it as a “genetic set point.” How old our parents and grandparents were when they died has some effect on the probability of how long we live. Healthy habits can add years, but the upside is less pronounced than bad habits, which can shear decades off a lifespan.
How should we live?
Don’t give up!
For scientists searching for longevity-related genes, the new evidence underscores the urgency to look for the biological mechanisms behind very long lifespan. 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 numbers for how many years healthy living could add to an individual person’s life trajectory, from five to 20, they all agreed there was some play in the system. What’s more clear is that unhealthy behaviors can sharply decrease it.
“What is your starting point? You actually don’t know that. We have no way of measuring that,” Scheibye-Knudsen said. “So unfortunately, or fortunately depending on how you look at it, that means you should not smoke, you should drink moderately and eat your vegetables.”
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