Now or Never?

Although scores of scientists are studying the biology of aging, they disagree about when--if ever--we'll be able to control the process.

In the late 1980s, when gerontologist Caleb Finch of the University of Southern California was penning his biology-of-aging classic, Longevity, Senescence, and the Genome , he received worried queries from academic reviewers who were perturbed by a proposed chapter title: "Negligible Senescence." Finch had coined the expression to describe a state in which an organism's statistical chance of death remains unchanged as it grows older; some rockfish, for example, survive and continue reproducing for an astonishing two centuries. Unaware of such evidence, the reviewers blanched at the concept. But Finch persisted, and in his final text even implied that if certain kinds of animals could apparently escape the ravages of aging, scientists might be able to orchestrate a similar effect in other species as well.

Ten years later, the term "negligible senescence" has been adopted by other scientists and is now the focus of a heated debate over the forseeability of human life extension--a discourse driven in large part by a software engineer-turned-gerontologist named Aubrey de Grey. In 2000, de Grey--of the University of Cambridge, U.K.--organized a roundtable discussion about the possibility of coming up with therapies that would postpone aging indefinitely, treatments that de Grey calls "strategies for engineered negligible senescence" (SENS). The group, which included University of California , Berkeley , biochemist Bruce Ames and Lawrence Berkeley National Laboratory gerontologist Judith Campisi, concluded that within ten years, a combination of already known and not-so-distant biotechnologies could allow scientists to reverse aging in mice. In a 2001 paper in the Annals of the New York Academy of Sciences , the SENS panel noted that such an achievement would spark an intense scientific race to extend the result to humans, with success potentially occurring "rapidly thereafter."

In contrast to de Grey's gung-ho scenario , other gerontologist take a considerably more pessimistic stance. Behavioral geneticist Richard Sprott, executive director of the Bethesda, Maryland-based Ellison Medical Foundation--a major funder of research on aging and of Crossroads' sister website SAGE KE--considers the prospect of controlling aging so unlikely that he won't even offer an alternative time frame to counter de Grey's. "I don't think it's likely in any time frame," he says. The two air their differences in this month's SAGE Crossroads Webcast debate--"How Soon Until We Control Aging?" The discussion won't resolve the question of whether life extension is just beyond the horizon--only the passage of time can do that. But the argument nevertheless has pressing ramifications: If most scientists doubt that they can ever learn how to regulate the aging process, research toward that goal could go unfunded.

A kind of gerontological gadfly, de Grey has made a habit of challenging skepticism about stalling or preventing aging. In a recent paper in Experimental Gerontology , he upbraided his peers for holding deeply pessimistic views "on the basis of extraordinarily ill-founded arguments," and for failing to work towards the discovery of antiaging medicines that may well be within their grasp. Among the gerontological platitudes that de Grey aimed to debunk: "There's no evidence that aging can be appreciably altered"; "There's so much in biology that we don't remotely understand;" "We must say nothing to cause optimism until we succeed in mice"; and, "We'll be seen as charlatans."

Most scientists who take the prospect of life extension seriously hope to achieve it by slowing the rate of aging. But de Grey's argument centers on the counterintuitive claim that reversing aging might not be any harder than retarding it. Advocating an "engineer's approach" to inventing antiaging medicines that would build a longer-lasting body, de Grey says we should think about preserving ourselves in much the same way that we preserve houses. In other words, let damage accrue and then repair it, rather than trying to prevent or slow the accumulation of damage by intervening in the complicated metabolic processes that precipitate it. De Grey, for example, doesn't have much use for the ongoing attempt to derive drugs that would mimic the effects of calorie restriction, a regimen that has been shown to slow aging in mice. "This is, to my view, completely wrongheaded--not the way to go about things at all," he says. Instead, de Grey advocates biotech interventions such as engineering cells to more effectively break down the detritus left behind by metabolism.

A sense of urgency pervades de Grey's approach. He argues that to successfully control aging, researchers must adopt a new perspective on the problem. At present, de Grey doesn't think the right research is getting done--which is why he says he wants to debate Sprott and potentially win him over. "He's the sort of person who, in my view, needs to have a more optimistic attitude," says de Grey, "or else he won't fund the correct research."

But even gerontologists who share de Grey's general bullishness wonder about the feasibility of skipping over age retardation and leap-frogging straight to age reversal. "I wouldn't choose that as my first strategy," says Finch. "I'd choose a strategy of finding out, at one fundamental level, whether you can block the accumulation of damage in the key molecules that drive the aging process."

Sprott, for his part, doesn't take a rosy outlook on either philosophy. He says that de Grey's optimism "entails a basic misunderstanding of the biology of aging," in particular an underestimation of the complexity of aging processes. "We can't get hormone replacement therapy for menopausal women right," Sprott says. "What makes us think that we can regulate the whole life span successfully, which is vastly more complicated?" Nevertheless, Sprott says Ellison funds a considerable amount of research by gerontologists hunting for the Fountain of Youth. Even if such studies don't lead to life extension, Sprott says, they could have "significant impact on reducing the consequences of age-related diseases."

Clearly, Sprott and de Grey lie at radically opposed ends of a continuum of opinions. Sprott says he's probably outdone in his pessimism only by gerontologist Leonard Hayflick, who decades ago discovered that adult cells themselves become senescent over time, but who has since written very critically of the idea of life extension. So even as some ethicists begin to worry about the repercussions of boosting longevity for individuals and society, the scientists who would presumably engineer this revolution remain of two minds about whether it will actually ever happen.

Chris Mooney is a freelance writer living in New Orleans , Louisiana . He's happy to take bets on how soon life extension will happen .