Unraveling the secrets of the aging process could lead to lives that are healthy and decades longer If there were a pill that could add two decades to your life, would you swallow it? Not if you're like most people scientist Matt Kaeberlein asks-they see it as an invitation to purgatory. "Why would I want to be old for an extra 20 years?" they say. But when the University of Washington longevity researcher dangles the prospect that those extra years would be spent spry and hale, not enfeebled and ill, they listen up. Researchers like Kaeberlein are learning that the aging process-not only how long we live but how well-is remarkably elastic, and that it can be manipulated. The lives of lab animals have been dramatically stretched in several ways-by tweaking their genes, feeding them drugs, changing their diets-that seem to make them age more slowly while prolonging good health. In theory, these strategies all do the same thing: fool the body into reacting as it would to a harsh environment, going into survival mode. The question is whether such techniques also can be made to work-safely-in humans. Scientists like Cynthia Kenyon, a geneticist at the University of California-San Francisco, want to try. Kenyon found in the 1990s that by tampering with a single gene associated with aging in nematodes, roundworms no bigger than one of the commas in this sentence, she could double their normal three-week life span. Deactivating the gene, she discovered, kicked in a "fountain of youth" gene that juiced up the worms' defenses against a slew of ills-extreme heat, oxygen deprivation, starvation, and disease. They lived longer and stayed younger; at six weeks, twice the nematodes' usual life span, they looked to be in the prime of life. It turns out that humans have both of those genes, and certain variations are enriched in centenarians. Now Kenyon is hunting for drugs that could turn on the fountain of youth gene in human cells. The secret of slowing down human aging would be one of the greatest discoveries in medical history, says S. Jay Olshansky, a biodemographer at the University of Illinois at Chicago. While aging itself is not a disease, postponing it, he says, would simultaneously postpone the risk of our biggest scourges-cancer, heart disease, stroke, diabetes, Alzheimer's. What follows are three hot areas under investigation: cutting calories, developing drugs to mimic a lower-than-normal calorie diet, and deciphering the genetics of the oldest of the old. Fewer calories Hundreds of studies since the 1930s have shown that a below-normal intake of calories slows aging and greatly extends healthy life spans in organisms as simple as yeasts and as complex as rats. The journal Science recently reported that rhesus monkeys (our evolutionary cousins) whose daily calories were reduced 30 percent for 20 years had one third the risk of developing age-related illnesses such as diabetes, cancer, heart disease, and brain deterioration compared with normally fed monkeys. That suggests "quite convincingly" that their aging is being slowed, says Richard Weindruch, a professor of medicine at the University of Wisconsin whose group is leading the ongoing study. (He'll have to wait a good while, however, to see if they live longer, since rhesus monkeys have been known to survive for 40 years.) In another study, called CALERIE, researchers are investigating the effect of cutting calories by 25 percent for two years for people of roughly normal weight to see if they undergo the same sorts of changes seen in animals. There's reason for thinking they will, says John Holloszy, a professor of medicine at Washington University in St. Louis and a principal investigator of the study. He and a colleague also have been tracking members of the Calorie Restriction Society International, or "Cronies," as some call them, who curtail their calories-typically by about 30 percent-in pursuit of better health and long lives. They are "powerfully protected" against type 2 diabetes and heart disease, says Holloszy, with clean arteries, low blood pressure (60-year-olds have the levels of children), low cholesterol, and much younger hearts than age-matched control subjects who eat a typical American diet. Successful screening measures such as a Papanicolaou test, HPV polymerase chain reaction testing, or both may be daunting to achieve, but there is meaningful hope that prevention efforts will ameliorate the effects of HPV-related oropharyngeal cancer."
