Other scientists have approached questions of human aging from a completely different direction, studying people who have achieved exceptionally long lives. One part of that research has pointed to genetic mutations that seem to be concentrated in centenarians, people who live beyond 100 years. Those gene variants are involved in some of the same processes that regulate metabolism and immunity, protecting cells in model animals.
These researchers are also finding that much of the human life span doesn’t just depend on characteristics people are born with, but rather on a host of other factors: lifestyle, relationships, environment, psychology. That might seem like common sense, but the centenarian studies give it scientific heft.
Research on so-called blue zones—a handful of regions that boast unusually high numbers of centenarians—has identified such hot spots as the interior mountains of Sardinia. There, the most salient local trait isn’t genetic, but rather a propensity for youthful exercise. It’s a region of shepherds, and many of the men who live to advanced ages spent their early lives walking long distances over steep terrain.
People in blue zones also tend to have common dietary habits. They eat smaller meals, have their last meal in the late afternoon or early evening, and consume lots of whole grains and vegetables—practices that are in line with modern dietary research. Social connections are crucial, too. In Okinawa’s blue zone, a cultural tradition called moais creates groups of five people obligated to be intimate, lifelong friends. That resonates with the idea that centenarians who have stronger social networks before reaching old age might fare better.
Psychology seems especially influential. Many centenarian studies point to the importance of mental resiliency and openness to new experiences. “Old people, especially centenarians, are confronted with key losses in all domains—health, mobility, loved ones—yet they seem happy and able to deal with those limitations,” says Daniela Jopp, a psychologist at the University of Lausanne who studied centenarians living in New York City. “Centenarians have quite a few psychological strengths that can buffer and protect them from difficulties.” Research on centenarians in the U.S. state of Georgia emphasized the importance of traits such as enthusiasm, warmth and self-discipline, with the single greatest predictor of health being their own perception of it. Optimism was literally healthy.
Cause and effect is tricky here. Someone who has managed to survive for a century might simply feel happy as a result. But it also may be that centenarians benefit from genetic traits that help them feel more upbeat—and that disposition, in turn, minimizes cellular damage. Leonard Poon, former director of the University of Georgia’s Institute of Gerontology, notes how people with a genetic variant linked to late-onset dementia and diabetes are more prone to stress than people who don’t have that mutation. It’s possible that their genetic makeup amplifies the effects of stress, which in turn accelerate the cellular breakdowns of aging. “Both psychology and biology would act synergistically,” says Poon. “The study of such interactions is the exciting new frontier.”
While lab-based gerontologists chafe at the notion that lifestyle alone will provide a longevity breakthrough, most also doubt that drugs by themselves will suffice. “I don’t believe that if you’re doing whatever you want, and then take one or two drugs, you’ll then live long and healthy,” says Fontana. “Social relationships, exercise, sleep, avoiding exposure to pollution—you can’t get all that with a pill.”
Finally, beyond the question of what will be required to make human lives longer and healthier is the matter of who will benefit. Massive health disparities already exist between those with different levels of wealth, and in the United States, the poorest 1% of Americans live an average of 12 fewer years than the richest 1%. If longevity breakthroughs carry a high price tag—such as that of everolimus, a cancer drug that could have antiaging effects and can cost more than $7,000 per month—the cost could exacerbate those differences.
“When we finally get the magic cocktail to make us live longer, will it be so crazily expensive that only a few people will have access to it and be able to benefit?” asks Raul Mostoslavsky, a molecular biologist at the Mass General Cancer Center and a faculty member at the Broad Institute.
Public health policy and social engineering aimed at prolonging lives might be as important—and as difficult—as finding the next aging breakthrough. “The question is,” says Fontana, “how can we change the system to give everyone the longest, best lives they can lead?”