A Wrinkle in Time; Do You Have to Age? How Science Is Finding Ways to Help Your Cells Say No

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Byline: Mary Carmichael and Jennifer Barrett Ozols

Though death is still as inevitable as taxes, future generations may age more slowly and live significantly longer. Here are five scientists in the vanguard of research, offering new insights into the biochemistry of aging--and opening the door for life-lengthening drugs. Their approaches vary, but they share the belief that the human life span is not fixed.

Enhanced: TARGETED GENES ARE MORE ACTIVE IN FIGHTING AGING

The "guess your age" booth at a carnival isn't often exactly right. But it's not usually as off-base as Cynthia Kenyon's colleagues. A few years ago Kenyon, a molecular geneticist, had one of her grad students cart a tray of worms around her lab, asking people how old they thought the worms were. Most said about 5 days. What they didn't know was that Kenyon had tinkered with the worms' genes. The squirmy creatures had the perfect health of 5-day-olds, but they were 144 days old--six times their normal life span.

Over the last decade, Kenyon's continuing work has shown that "you can make huge changes in life span so easily"--in worms, at least--by changing hormone levels and enhancing the effects of fewer than 100 genes. Some of the target genes produce antioxidants; some make natural microbicides; some are involved in transporting fats throughout the body, and some, called chaperones, "keep the cell components in good working order," says Kenyon. What they all have in common is their effect on aging. The more active the genes, in general, the longer an organism is likely to live.

When Kenyon's work with worm genes was first published in 1993, skeptics predicted it wouldn't translate well to humans. One hundred forty-four days might be ancient for a worm, but a far more complex human being can already expect to live about 200 times longer than that. Scientists still don't know exactly why the life spans are so different, much less what a change in a worm's life span might mean for a person's. Nonetheless, much of the cellular machinery in worms closely resembles that in higher mammals. That finding has opened the door for a neutraceutical company, Elixir, which is trying to develop a drug that would yield the same kind of results as Kenyon's genetic tampering. "I'm not saying that with a few changes humans could be immortal," she says. "But it'd be like looking at an 80-year-old and thinking he was 40." Who could object to that?

Stressed: CHRONIC TENSION MAKES CELLS DETERIORATE FASTER

If you've ever blamed stress for new wrinkles or gray hairs, you may have been right. "As a society, we have a deeply held belief that life stress causes premature aging, but there's actually been very little empirical evidence to show this," says Elisa Epel, assist-ant professor of psychiatry at the University of California, San Francisco.

Until now. In a UCSF-led study published this past fall in Proceedings of the National Academy of Sciences, Epel and her colleagues found that chronic stress--or even the perception of stress--significantly shortened the length of telomeres, the tips of chromosomes within cells that can be used as a measure of the cells' aging process. The shorter the telomere, the shorter the cell's life span and the faster the body's deterioration. As more cells die, the effects of aging kick in: muscles weaken, skin wrinkles and eyesight and hearing worsen.

Epel and her colleagues studied 39 women between the ages of 20 and 50 with children suffering from serious chronic conditions, like cerebral palsy, and compared them with 19 mothers in the same age group with healthy children. The longer a woman had been caring for a sick child, the shorter her telomeres--and the greater her oxidative stress (a process that releases DNA-damaging free radicals).

But what startled researchers more was that the most profound differences were tied to the women's perceptions of how much emotional strain they were under, regardless of whether their children were healthy or sick. …