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A massive genetic study of people who lived for more than 100 years has found dozens of new clues to the biology of aging.
The findings won’t be turned overnight into longevity elixirs or lifespan tests, nor do they untangle the complex interactions between biology, lifestyle and environment that ultimately determine how long — and how well — one lives.
But they do offer much-needed toeholds for scientists studying the basic mechanisms of aging, which remain largely unexplained.
“It shows that genetics plays an extremely important role at these extreme ages. And it begins to be a not-unsolvable puzzle,” said Boston University gerontologist Thomas Perls. “If we start looking at these genes and what they do, we better understand the biology of extreme longevity.”
Published July 2 in Science, the findings come from gene tests of 801 people enrolled in the Perls-founded New England Centenarian Study, the largest study in the world of people who’ve lived past 100.
People who’ve reached that mark tend to have lives that are not only exceptionally long, but unusually healthly. Unlike most people, they rarely develop diseases of aging — such as heart disease, metabolic disease, cancer and dementia — until well into their 90s. They’re also more likely to bounce back from disease, rather than entering a spiral of declining health.
That manner of aging is a goal for most people, and a public health necessity. Modern medicine has had success in slowing individual aging diseases, but when one is postponed another soon emerges. Americans are living longer but not healthier. Nearly three-quarters of U.S. health spending now goes to treating diseases of aging. That proportion is rising.
In the last decade, scientists using animal models of disease have identified numerous genes and biological pathways implicated in aging. That animal research is valuable, but the gold standard of longevity science involves long-lived people.
Other studies suggest that whether or not someone lives to their 80s is mostly a result of common-sense lifestyle choices: moderate drinking, no smoking, plenty of exercise, a vegetable-centric diet and low stress. But beyond that, “genetics plays a stronger and stronger role,” said Perls. The concentrations of telltale gene profiles found by his group suggest “that the genetic influence is very, very strong.”
Perls’ team surveyed the genomes of 801 centenarians, focusing on “hot spots” where people are most likely to have mutations. They compared the results to genome scans of 926 random people from the general population. From this came a list of 70 gene mutations found mostly in the centenarians. After comparing those to genome scans of 867 people with Parkinson’s disease, the list was whittled down to 33 key mutations.
The researchers used these results to develop statistical models of longevity-associated gene profiles. Used to evaluate anonymized sample genomes, the model could predict whether the sample came from a centenarian with 77 percent accuracy, underscoring the importance of genetics in extreme long life.
Centenarians also tended to fit one of 19 different gene profiles. Some of the profiles tracked with especially low rates of cardiovascular disease, dementia and hypertension or diabetes, suggesting specific genetic pathways for those diseases.
Perls emphasized that the profiles — which came from Caucasians, and are likely different in other ethnic groups — are not intended as guides for drug cocktails or diagnostic tests.
“We’re quite a ways away still in understanding what pathways governed by these genes are involved, and how the integration of these genes, not just with themselves but with environmental factors, are all playing a role in this longevity puzzle,” he said in a press conference.
Other were excited about the findings, but echoed Perls’ restraint.
National Institutes on Aging neuroscientist Donald Ingram called the study a “very impressive genetic and statistical tour de force,” but one that leaves environmental influences unexplained.
According to Perls, one of the study’s most intriguing results is that roughly 15 percent of the general population has some of the longevity-associated genes. Yet only one in 6,000 people currently live to be centenarians — many fewer people than seems to be suggested by the genetics.
Some of the discrepancy can likely be attributed to standards of infant care and public health at the beginning of the 20th century, when these centenarians were born, said Perls. Lifestyle and genetics are also sure to play a part. There will also be genetic factors missed by the study’s narrow focus on hot spots.
According to Jackson Laboratory gerontologist David Harrison, who called the findings “very interesting,” researchers will use animals to explore the roles of genes and pathways flagged in the study.
The findings will also need to be replicated and expanded in more human studies, said National Institutes on Aging gerontologist Winifred Rossi.
“It’s groundbreaking work,” she said. “But science is not fast. It’s slow. It takes a lot of steps to get to something with an impact. We’re only at the start of exploring longevity.”
