Health Checkup: How to Live 100 Years

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Separately, biologists and geneticists have pursued the secret to longevity on a cellular or molecular level, first in animals and more recently in people. The goal is to identify genes associated with slowing normal aging and avoiding the chronic illnesses that accompany it.

But with advances in genomic technology that allow scientists to scan thousands of genes from a single sample at a time and then link them to specific functions in the body, researchers on aging can finally begin to knit together their two strands of inquiry. The result is an intricate tapestry that is starting to reveal exactly how we can best push the limits of life span. These findings in turn could eventually lead to drugs or other compounds that mimic such natural mechanisms, stretching lives a bit longer by keeping the genome in good repair, for example, or by boosting the body's defenses against free radicals. If we can't stay chronologically young, the scientists reason, we can at least live and feel as if we are.

"We are going through a revolution," says David Sinclair, a professor of pathology at Harvard Medical School, who has studied aging in animals and co-founded Sirtris, a biotech company developing antiaging compounds. "I think we might have our first handle on the molecules that can improve health." Even if we are not endowed with the genes that can ease us into our 100s, most of us can certainly learn something from families like the Hurlburts, who apparently are.

Of Yeast and Men
Until relatively recently, the best clues about the factors involved in growing old came not from healthily aging humans but from other, decidedly less interesting species. Take, for instance, yeast. These organisms provided the first hints about how much of aging was due to genes and innate biology and how much was the product of other variables. It was yeast and, later, flies and rodents that provided the first findings about caloric restriction, the intriguing hypothesis that a drastically reduced intake of calories can extend life span.

While there is no firm evidence that the same phenomenon occurs in humans, researchers like Leonard Guarente at the Massachusetts Institute of Technology found yeast genes that appear to cause a food-restricted metabolism to use energy more efficiently, burning through caloric inventory at just the right rate to maintain life-sustaining processes while keeping something around for future use. Sinclair calls these survival genes. When they're activated, he says, they stabilize DNA and, in the yeast's case, extended survival 30% beyond what is normal. So far, Sinclair and others have identified a dozen similar genes in people. What they are hoping to do is find a way to turn these pathways on without forcing the rest of the body to hunker down in survival mode.

But while genes are certainly an important component of aging, they may not be the most relevant factor, if only because we don't have much control over them. The good news is that according to animal studies, only about 30% of aging is genetically based, which means that the majority of other variables are in our hands. Not only can getting such factors under control help slow the aging process before it starts, it can also help those who are already in their golden years improve their fitness and strength. Recent studies have shown, for example, that when seniors from ages 65 to 75 exercise with resistance weights, they can improve their scores on cognitive tests of memory and decision-making. Other research, in Germany, found that regular physical activity lowers the risk of developing cognitive impairment in people over age 55.

The 70%-30% split between environment and genes, however, doesn't apply to everybody. For lucky oldsters like those who qualify for the LLFS study, the reverse seems to be true. Perls has found that in centenarians, it's principally genes that are the secret to extra years. That's not surprising, since these people represent the extreme limit of our species' life expectancy.

But the centenarians' happy accident of birth may benefit the rest of us too, if Perls and his colleagues are successful in their work. Their first goal is to draw a complete map of their subjects' genomes, to figure out what makes their mortality clocks tick so slowly and for so long. "We think centenarians are going to be really powerful when it comes to genetic variations or combinations that are important to living to really old age," says Perls.

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