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How long you live may depend much more on your genes than scientists thought

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Three decades ago, a famous study of Danish twins found that our genes “only moderately” influence how long we’re likely to live. Longevity, the authors estimated, was about 25 percent heritable, meaning the remaining three-quarters was determined by environmental factors and lifestyle choices, such as diet and exercise. Most subsequent studies found heritability to be somewhere in the 20 to 25 percent range, and 25 percent is now widely accepted. But a new study more than doubles it, suggesting lifespan may be more genetically fixed than we thought.

The study, which was published today in Science, arrives at this dramatic increase by reframing how scientists think about longevity. Rather than lumping all deaths together, the researchers distinguish between two kinds: “intrinsic mortality” comes from built-in biological aging processes and genetic mutations, whereas “extrinsic mortality” comes from outside causes, such as accidents and infection. Early longevity studies analyzed groups of people who were born in a time of widespread extrinsic mortality. That skewed previous estimates of heritability, says Uri Alon, a systems biologist at the Weizmann Institute of Science in Rehovot, Israel, and senior author of the new paper.

To sort out the effects of intrinsic versus extrinsic deaths on longevity heritability, he and his colleagues ran computer simulations of human mortality, calibrated using data from those previous twin studies. When they dialed extrinsic mortality down to zero, leaving only deaths caused by intrinsic aging processes, lifespan heritability roughly doubled. Surprised, the team performed a sanity check—the researchers calculated heritability in the traditional way for twins born between 1900 and 1935, an era when rapid medical advances steadily curtailed premature death. From one generation to the next, Alon says, “they have lower and lower extrinsic mortality, and we see that their heritability goes up and up.” Taken together, the results indicate that intrinsic lifespan—how long a person lives if they don’t die of an external cause—is about 55 percent heritable.

Kaare Christensen, an epidemiologist and professor at the University of Southern Denmark’s Danish Twin Research Center, who was not involved in the study, calls it “an interesting mathematical exercise” but notes that “in the real world, people die from both kinds of death.” There’s no actual discrepancy between the two heritability estimates, 25 and 55 percent, he says, because they’re measuring different things. Considering extrinsic mortality has declined so much in the past century, however, Alon argues that “the higher number is more relevant” for people born today. In reality, except for the most clear-cut cases of genetic causes (such as a genetic disease) or environmental ones (such as a lightning strike), it’s hard to separate extrinsic and intrinsic factors.

Whether or not the new estimate offers a more realistic picture of lifespan heritability, it highlights the importance of genetics in extending lives, says Sofiya Milman, a scientists who studies aging and longevity at the Albert Einstein College of Medicine. She’s one of many researchers who are trying to understand how centenarians’ unique biology protects them from age-related disease. “We’re hoping to create therapies that will mimic those intrinsic factors,” Milman says, “and make them accessible to people who didn’t win the genetic lottery.”

Most of us are unlikely to break 100 without the right set of genes—or at least drugs designed to replicate their beneficial effects. Until such treatments become available, though, a healthy lifestyle remains the best path to living longer. Even if exercise, sleep, and a balanced diet only contribute 45 percent to lifespan, evidence shows they can still add 10 years or more to a person’s life. “Those things will be helpful,” Milman says, “irrespective of your genetic makeup.”

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https://static.scientificamerican.com/dam/m/6d14c3894dbc61b9/original/GettyImages-1781825521_resized.jpeg?m=1769712819.473&w=900Amr Bo Shanab/Getty Images

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Click the link below for the complete article:

https://www.scientificamerican.com/article/how-long-you-live-may-depend-much-more-on-your-genes-than-scientists-thought/

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