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GETTING ON IN YEARS:

A multitude of maladies // and decades of decrepitude // or, with a pill or a tweak of the genes // 
a painless, peaceful, dignified decline?

Longevity Research: Is Aging a Disease?

By Brandon Keim // Photo Illustrations by Julien Pacaud // Spring 2010
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longevity

Julien Pacaud

When David Harrison began studying aging, he had yet to experience its effects. In his late twenties, he was fit, healthy and impervious to harsh New England winters; on all but the coldest days, he’d strap on cross-country skis and head for the Maine hills. Now, though, at age 67, he sees in himself the progressive decline he has long observed in the mice and other animals of his research. A decade ago, doctors removed a prostate tumor before the cancer spread to his bones, but other problems have accumulated. Some, such as high blood pressure and high cholesterol, are easily treated, but they’re accompanied by elevated insulin levels and weight gain—a constellation of disorders called “metabolic syndrome,” which often precedes heart disease, diabetes and stroke. Dieting, exercise and drugs only slow its progression. And he now spends winters in North Carolina, where the milder climate seems to help him dodge another apparent symptom of his advancing years: chest colds that linger for weeks. “I feel the shadow of aging’s progression growing closer,” Harrison says.

He’s careful to say “aging,” not “age,” a crucial distinction in his work as a gerontologist at the Jackson Laboratory in Bar Harbor, Maine. Some lucky people reach their nineties or beyond without being struck down by any of the diseases on a long list—heart failure, diabetes, stroke, Alzheimer’s, Parkinson’s, cancer—that become much more common after middle age and kill most Americans. And though those maladies are often grouped together as “diseases of aging,” that’s usually just a convenient catchall—they’re what tends to happen when you get old. Each illness has its own phalanx of researchers striving to understand its unique causes and find ways to prevent or treat the damage it does. But some scientists take a more holistic view. They think aging itself is the issue, and that when you trace heart disease, cancer and Alzheimer’s back to their roots, they all seem to stem from the same problems that span multiple body systems and lead them to ultimately malfunction.

To support this argument, researchers point to the fact that many diseases of aging seem to share networks of genes and molecular pathways. Harrison, like other longevity researchers, emphasizes that his work to decipher and improve those biological processes is not a quest for a fountain of youth—he doesn’t think people can live indefinitely. Indeed, “longevity research” may be a misnomer. Though these scientists routinely produce lab animals with exceptionally long lives, their goal for humans is less to help them live longer than to fulfill their allotted span in good health. They’re working to develop drugs that might delay the onset of multiple diseases of aging by acting on shared causes. That’s preferable, they say, to standard practice today—fighting off diseases one at a time in a process that provides not health but prolonged decrepitude.

Despite their success in producing long-lived animals, however, scientists so far have only a fragmentary understanding of the extraordinarily complex mechanisms that appear to determine why some mice and other species, under certain circumstances, survive so much longer than others do. One method—caloric restriction—has been a particular focus because it has seemed to be a surefire method for extending longevity and thus might reveal biological secrets that could help push back the age at which so many human diseases take hold. Yet the approach now appears to work only in some animals, further complicating research that was thought to be well understood. Meanwhile, other scientists are approaching this puzzle from a different angle, studying people who live long, healthy lives to find out what makes them special—an approach that advances in genomic analysis should make increasingly productive.

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The Time of Your Life

Do people who struggle with health problems as they age share biological similarities?

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1. “Prolonging the Life Span,” by C.M. McCay and Mary F. Crowell, The Scientific Monthly, November 1934. An account of the discovery that a calorie-restricted diet extends the lives of laboratory rats, sparking decades of research that eventually led to investigations of longevity’s molecular mechanisms.

2. “Rapamycin Fed Late in Life Extends Lifespan in Genetically Heterogeneous Mice,” by David E. Harrison et al., Nature, July 9, 2009. The authors describe findings that were later independently replicated in three research centers, working with mouse populations as genetically diverse as those of humans.

3. “New Model of Health Promotion and Disease Prevention for the 21st Century,” by Robert N. Butler et al., British Medical Journal, July 8, 2008. The authors argue that slowing aging could yield greater benefits than treatments for individual diseases.

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