WE HUMAN BEINGS are the onlyanimals capable of contemplatingour own demise. We mourn, wememorialize, we philosophize andwe pray. And when it happens onrare occasions that we "cheat"death, we believe, just for amoment, in immortality.

Today scientists are tempting fatein ways never before imagined asthey demystify the secrets oflongevity. Biochemist Bruce Amesbelieves that nutrients can repairdamaged cells and make them"young" again. Molecular biologistJudith Campisi is studying how tokeep cells from aging.

Both believe that while there maybe no actual Fountain of Youth orscientific

Dorian Gray in a bottle, reversalof aging and an extended lifespan are now on the horizon.

AT 74, BRUCE AMES looksevery bit the part of an elderlygent, with his white hair, bifocalsand quaint bow tie. Ames is a bigidea man. Genes. Cancer.Nutrition. And now aging. He haspublished more than 450 articlesand is becoming one of the mostfrequently cited scientists on theplanet. "I told a colleague recentlythat 1 was doing the best work inmy career," says Ames, who is aprofessor of biochemistry at theUniversity of California atBerkeley, "and he looked at

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consumed by an average cell, themitochondria convert 95 percent to helpturn food into fuel. Every time webreathe, we're giving a boost to our cells.

During that process, however,mitochondria sometimes "misplace"electrons. Like money flying out the backof a Brink's truck careening around acorner, these electrons-now called freeradicals-scatter around inside cells,bonding indiscriminately with othermolecules. This mischief is calledoxidation, and it allows free radicals tobecome chromosomal rototil lers,mangling DNA at will.

Too many free radicals create a kind ofcellular pollution that shoots down ourenergy levels. Too much damaged DNAcauses cell mutation (which can causecancer) and cell death. Both are signs ofaging. In 1990 Ames and his colleaguesat the University of California at Berkeleyannounced that they'd discovered twiceas much free radical damage in tissuesof two-year-old rats as in two month-oldrats. Ames's team had found a cruciallink between oxidation, DNA mutationand age: Free radical oxidation doesn'tjust rise with aging-it causes it. The morethat mitochondria "leak" free radicals, themore those radicals end up damagingthe mitochondria, which in turn leak evenmore free radicals.

This vicious cycle gets worse as we getolder. It is the ultimate biological irony:The thing we most need to live oxygen-isthe very thing killing us. Regarding hisown biological clock,

me and said, 'Bruce, you've been tellingme that for 30 years.' I guess that meansmy enthusiasm genes are undamaged."

AMES WOULD KNOW if they were.Damaged genes have been his businessfor half a century. In the 1950s, Ames wasa researcher at the NIH. His researchultimately proved that genes damaged bycertain chemicals often give rise to cancer.By the 1970s, the "Ames test" was theworld's most widely used method foridentifying potential carcinogens ineverything from clothing to hair dye topharmaceuticals.

Ames has a penchant for mixing plaids; atthe same time, his mind is relentlesslymixing and matching ideas. "It's justproblem-solving:' he says of hismethodology. "If you have two odd facts inyour head and suddenly they fit together,you see a new way of explainingsomething."

Two odd events kept jangling about inAmes's head: the rise in cancer and theincrease in free radicals with age. Freeradicals are molecular miscreants thatcreate havoc inside cells by stripping othermolecules of vital electrons. Was there adirect link between free radicals andaging? he wondered.

Ames began by looking at mitochondria,where free radicals are produced.Mitochondria are tiny structures insidecells that act like furnaces, manufacturingmost of the energy that is used by thebody. Mitochondria are spectacularlyefficient. Of the oxygen

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Ames, surprisingly, has been somethingof a slacker. He likes to joke that he getshis exercise by "running" experiments,"skipping" the controls and "jumping" toconclusions. His wife of 40 years,biochemist Giovanna Ferro Luzzi, heardthe joke for the 50th time recently andexacted her revenge: "She got me apersonal trainer."

Ames says he has time for only about anhour a week with the trainer, butGiovanna insists they walk the two milesto their favorite Italian restaurant, Oliveto,for lunch at least three times a week.

Visiting his wife's native country in themid-I990s, Ames saw that a dietarysupplement known as acetyl-L-carnitine,or ALCAR, was sweeping Italy. It wasbeing marketed as a pick-me-up, andAmes understood why: ALCAR is anatural biochemical that helps cellsproduce energy. He suspected ALCARmight slow, or even reverse, aging, andbegan feeding it to his old rats. Theyloved the stuff. Within weeks, theyappeared re-energized.

There was a problem, however. TheALCAR did not lower the level of freeradicals. Ames decided to add anothersupplement to his rats' diets, theantioxidant alpha lipoic acid.

"With the two supplements, these oldrats got up and did the Macarena," saidAmes. "The brain looked better; theywere full of energy." It was the equivalentof making an 8O-year-old person lookand act middle-aged. In 1999, Ames anda colleague, Tory Hagen, founded theJuvenon company in order to sell theenergy formula.

The pill, available over the Internet,includes 200 milligrams of alpha lipoicacid and 500 milligrams of acetyl-Lcarnitine, but the two nutrients can bepurchased at any health food store.

"I don't want to over-hype it," cau-

tions Ames, who has no financial stakein the company. "We have to wait forthe results of the human trials."

Right now, Ames and his researchersare studying whether the pill canimprove circulation in cardiovascularpatients by relaxing blood vessels,thereby possibly reducing the risk ofheart attack or stroke. Ames takes adose of his own supplement twice aday. "I'm very optimistic."

The ultimate irony: The thing we needmost to live-oxygen-is what's killing us.

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IN HER BASEMENT OFFICE inBerkeley, Judith Campisi sits on theedge of a chair and speaks with awide-eyed enthusiasm usuallyreserved for first year graduatestudents. Piles of papers rise from thefloor like unsteady chimneys,

some nearly as tall as the four foot-ten scientist. Campisi is a seniormolecular biologist at LawrenceBerkeley National Laboratory. Anexpert in the genetics of aging, shebelieves that altering genes to extendlife span may not be far off.

Campisi, 54, is a proponent of the"double-edged sword" theory ofaging: The same cellular process thatkeeps us healthy in.our youth also

causes our bodies to age in later years.

Her research focuses on the telomere,a structure containing a repeated DNAsequence that is found on both ends ofevery chromosome in the human body.In 1990, Calvin Harley, now the chiefscientist at Geron, a biopharmaceuticalcompany, discovered that as cellsdivide, the telomeres of the new cellsare shorter.

Later, it was shown that in some cellsthe telomeres also got shorter with age.When telomeres become too short,they send a signal to the cell to stopdividing, and a natural state calledsenescence ensues. Campisi believesthe primary function of senescence isto fight off cancer.

"Senescent cells are not dead;' shesays. "They're perfectly alive, but whatthey can never, ever do again is divide.And if you can't divide, you can't form atumor."

Campisi's research has shown that thelonger we live, the more senescentcells our bodies accumulate, and it'sthose cells, she says, that may play aleading role in making us look and feelold-causing wrinkles, failing eyesightand chronic inflammation.

If she can prove this hypothesis,Campisi will have identified one of themain contributors to aging: We age notbecause our cells die, but becausethey stop dividing and start tomalfunction.

"One thing we've learned;' she says, "isthat you don't want cells to not'senesce' at all, because then you havecancer. What would be great would beto have some of the senescent cells

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die, so they don't accumulate withage. That's what we're working on."

Research, says Campisi, is a lot likeone of her favorite pastimes, cooking.A little of this, a little of that-the bestmeals are unplanned, the result ofintuition and experimentation. "Iconsider recipes advisory only," shesays.

Likewise in her research, Campisienjoys creating her own path,pursuing solutions not with asprinter's speed but at an ambler'space, taking the time to searchfamiliar territory for missed clues. "Ijust start doing this random walk,"she says, "and eventually I wind upwhere I need to go."

SOME SCIENTISTS, such as JayOlshansky, a professor in the schoolof public health at, the University ofIllinois at Chicago, express caution.The co-author of The Quest forImmortality, Olshansky says: "Whenwe

survive into old age, just as withautomobiles and race cars, thingscan start to go wrong."

Robert Lanza, medical director ofAdvanced Cell Technology inWorcester, Mass., shares this view."You can achieve immortality at thecellular level, but I don't see how itwould be practical in extending lifespan," he says. "Humans hit a wall at120 years.

"There's no question that in two orthree decades we'll be able to replaceevery part of the human body," Lanzacontinues. "But we're like tires. Thereare just so many times you can bepatched up." Ames and Campisiremain optimistic. Both share thebelief that a delay of aging is withinour grasp. Someday, they say, wemay all enjoy a very long and healthyextended middle age.

For current resources on looking andfeeling your best, check outrd.com/wellness.

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