Is Aging Inevitable

From turtles that don't seem to grow old to mayflies that live for only three hours, animals hold clues for making our own lives easier and even longer

02-01-1994 // Doug Stewart

Among the armaments of a British fort on the island of Mauritius, the oldest turtle on record once plodded as if it would live forever. When it finally succumbed, the cause was not illness or infirmity, but a freak accident. In 1918, still spry more than 150 years after its initial capture (or as spry as any giant tortoise is apt to be), it wandered through a gun port and died of the fall.

Turtles, you see, don't seem to die of old age. Whether giant tortoises or humble, box turtles, they don't steadily deteriorate just because they put on years; they don't senesce, to use the gerontologists' term.

"You can find an individual turtle that's sick and say that maybe it's senescent, but there's no evidence of senescence in turtles as a population," says Whitfield Gibbons, a turtle expert at the University of Georgia's Savannah River Ecology Lab in South Carolina. Rather, the armored reptiles persevere-lumbering, swimming, feeding, laying eggs-until something kills them. And something always does, eventually. That's not to say that turtles have discovered the fountain of youth. "As best I can tell," says Gibbons, "even young turtles look old."

Why an animal ages-or, in a turtle's case, doesn't age-is very much an open question in the world of research gerontology. The question sounds at first too obvious to deserve an answer-they age because they get old, right? Not really, it turns out. No one knows if animals die because their time is up-or because illness, injury or deprivation does them in.

"Can you look at pure aging in the absence of disease?" asks Huber Warner of the National Institute on Aging (NIA) in Bethesda, Maryland. "The pathological changes that we think of as aging are also pathological changes that we think of as disease." For Warner, the deputy associate director of the NIA's Biology of Aging Program, identifying precisely what aging is remains a central research question.

A host of new studies of animal aging is beginning to suggest answers, some unexpected, some hotly debated. Motivating the research is more than curiosity about elderly wildlife: An understanding of how animals age, researchers agree, could lead eventually to drugs and therapies to combat the afflictions of elderly humans.

But arriving at that understanding will take some doing. Consider: A mayfly in its adult stage, born without a mouth and living off energy reserves it's born with, has a life span as brief as three hours. A four-year-old mouse is elderly, as is a dog at 15 years, a horse or a chimp at 40. African elephants can reach 70. Among mammals in particular, a pattern seems to emerge: The bigger you are, the longer you live. (Humans, which have made it to 120 years, presumably have extended their allotment of years with hospitals, health food, step aerobics and the like.)

Observing this pattern, German physiologist Max Rubner theorized in 1908 that all mammals, pound for pound, expend the same amount of energy during their lifetimes. Raymond Pearl, a biologist at Johns Hopkins University, expanded on this notion in 1929, suggesting that each species has a fixed metabolic potential. If so, individuals with fast metabolisms would die sooner than would more sluggish members of the same species. The so-called rate-of-living theory of aging supposes that the daily act of living is harmful and that deterioration is an unavoidable outcome of cell metabolism-in short, that an animal's body steadily falls apart.

As a predictor of life span, the rate-of-living theory does appear to hold true for houseflies and many other insects. "If you put 200 male houseflies into a 1-cubic-foot cage, they'll live an average of 15 days," says Robert Allen, a biologist who studies aging at the Medical College of Pennsylvania. "If you put individual flies in small bottles with cardboard mazes to keep them from flying, they'll live on average for three months." Houseflies, unlike humans, don't benefit from a workout. "If we exercise, we probably live longer," Allen says. "If insects exercise, they just get tired."

Moreover, cold flies, whose metabolism is relatively slow, live longer than warm flies. That explains the handful of slow-moving flies that appear in your home each spring before you've even opened the windows; they've overwintered in some cold corner. Allen also reports the intriguing finding that the total amount of oxygen consumed by flies during their lifetimes, vigorous or sedentary, warm or cold, is almost identical. Discoveries like this have led to theories that oxygen consumption leaves a toxic residue that damages cells and ultimately helps kill the fly. Biological rust, in effect.

But if the large outlive the small, why do birds far outlive rodents of the same size? Why do cats outlive dogs? A different theory views an animal's life span as genetically programmed, like fetal development or puberty. This notion is known as the evolutionary theory of aging, and it supposes that natural selection has determined each species' life span.

The key is an adaptive benefit in each case, though the word "benefit" can be hard to reconcile with what actually happens to the creatures. Consider Pacific salmon. Within days of spawning, populations of adult salmon collapse in cataclysmic die-offs. The salmon don't simply die of exhaustion from propelling themselves upstream to their spawning pools. Rather, the cause is a grotesque onslaught of stress-related ailments: ulcers, infections, enlarged glands, devastated immune systems -all apparently triggered by a flood of adrenal hormones. It is as though Mother Nature had checked her watch and thrown a "hormonal death switch," as University of Southern California neuroscientist Caleb Finch and Stanford University gerontologist Robert Sapolsky have written.

What's tough on a parent can be fine for offspring, however, and therein lies one possible evolutionary justification for such fast-forward senescing. The dead fish, had they lived, wouldn't have helped raise their young. In fact, they might even have competed with their offspring for food-if adult salmon ate in fresh water.

Turtles, along with other nonsenescing animals like lobsters, clams and rockfish (none of them mammals), are at the other extreme. "In terms of evolution," says Gibbons of the Savannah River Ecology Lab, "the measure of success is passing genes on to the next generation, not how long you live." A long life in itself provides an adaptive benefit only in animals with social cohesion.

"Among primates, older individuals have acquired knowledge about the environment and can contribute to the success of their offspring's offspring's offspring," says Gibbons. "A turtle, once it lays its eggs in the ground, walks away." Since turtles, like salmon, show no parental care whatsoever, there is no evolutionary reason for them to live beyond the age of reproduction. And they don't. Healthy turtles never stop reproducing, no matter how old. The older a turtle lives, the bigger its total contribution to the gene pool-and the better its genes' chances of prevailing in the natural-selection sweepstakes.

Rates of aging for mammalian species generally fall somewhere between the extremes of the Pacific salmon's rapid degeneration and the turtle. Unlike the latter, a mammal's fertility begins to fall off as it ages, at least under laboratory conditions. In the wild, an animal is usually dead by the time it's too old to procreate. (Humans are a conspicuous exception.)

Among mammals, variations in how fast individuals in different species age have long perplexed biologists. A porcupine can live to be 20, for instance, while an opossum of the same basic size and metabolic rate is lucky to see its second birthday. Might quills have something to do with it? Yes, they might. Quills, quite obviously, reduce the chances that a porcupine will die young from a predator's attack. Far less obvious is how body armor could help determine innate life span. But natural selection works in wondrous ways.

An ongoing study by evolutionary biologist Steven Austad of the University of Idaho provides an unusually clear-cut illustration of the connection between aging and susceptibility to predation. Austad is studying Virginia opossums on an island off the Georgia coast, where they have evolved for thousands of years free of mammalian predators. Compared to mainland opossums, the island animals not only live as much as 25 percent longer but also stay fertile longer and age more slowly physiologically. Natural selection has presumably chosen different genes as advantageous on the island, and Austad thinks the absence of predators may be the main reason.

Virginia opossums are relatively defenseless, and few in typical mainland populations survive longer than two years. Austad asks: What if a gene that confers some benefit early in life also causes a late-acting genetic malady, one that kills off the few opossums that manage to live beyond two years? That gene will continue to be passed on, the good outweighing the bad. After all, very few of the animals live long enough to fall victim to the hypothesized defect.

On the island, however, the theory goes, opossums that inherit such a defect would be far more likely to live long enough to succumb to it. That's where natural selection could play a key role. If such a defect exists, lucky animals that don't inherit it would live longer and produce far more offspring than their handicapped rivals. With every generation, a smaller proportion of the population would be born with the genetic defect-and animals without it would age beyond mainland opossums, just like the actual island opossums.

A dramatic boost to the evolutionary theory of aging has come from the University of California at Irvine, where biologist Michael R. Rose and colleagues have been experimenting with geriatric fruit flies. In one population, Rose's group destroyed the eggs of all but the oldest members, one generation after another, so that only unusually long-lived flies became parents. Their descendants live 80 percent longer than do flies bred from a lineage of youthful ancestors. "That's the equivalent of a human living 150 years or even 200 years," Rose says.

The idea that genes can affect longevity is becoming widely accepted. More controversial is the idea of an actual longevity gene whose function is to control life span. Thomas E. Johnson, a behavioral geneticist at the University of Colorado, believes that there is such a gene, at least in the animals he studies, nematode worms. He uses chemicals to encourage the tiny worms to mutate, then searches through thousands of offspring to select those whose life spans have been extended by genetic accidents. His longest-lived worms live five weeks; three weeks is the usual upper limit. "We're 99 percent certain that these differences result from a single gene change," he says.

The purpose of experiments like these isn't to create immortality in the lab, of course. "No combination of genes is ever going to produce 40-year-old mice," Johnson notes. Nor 400-year-old humans. But the new genetic work is helping researchers understand animal aging and, by extension, human aging.

A gene's job in the body is to control and choose proteins manufactured by the cells. Ultimately, new drugs might mimic that task, making the later stages of human lives healthier, more comfortable and more productive. Finding ways to prevent Alzheimer's disease in particular is a key goal of research funded by the National Institute on Aging. The drug industry, meanwhile, has shifted close to half its funds for research and development-nearly $4 billion a year-into research related to aging.

Low-tech methods for aging research are also showing promise. One approach, studied since the 1930s but now arousing new interest, is to simply put animals on a diet. Numerous studies of mice, rats and other animals have found that populations fed one third to one half as much as what they would eat freely live up to 50 percent longer. Doubts remain about what conclusions to draw, however. Do the diets block aging itself or the diseases that accompany aging? Are diet-restricted animals doing well only in comparison to lab animals, which may have been pigging out and dying young? More philosophically, is the extra time worth it if you spend it hungry?

New large-scale studies are now under way, but already there is at least one telltale sign that diet restriction is a promising research direction: When the first beneficial results became clear, many of the human researchers themselves promptly went on diets. Just in case.

Freelance writer Doug Stewart is all too aware he's a member of a senescing species. Yet he's glad he's not a turtle.

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