United Public Domain Gold 2/United Public Domain Gold 2.iso/utilities/pu732.dms/pu732.adf/Mys00946.txt

Text File | 1995-03-07 | 37KB | 565 lines

 I

                                IEGELIXIRS OF YOUTHFHI


                          KIIn the twenty-first century
                 antiaging substances will revitalize our skin,
                           KIour organs--and our genes

                           BY ANN GIUDICI FETTNER AND
                                PAMELA WEINTRAUB

    During Prohibition Mama and her friends used to ride out into the still-
 rural area surrounding Atlanta to buy bootleg whiskey from Pop Adams.  In the
 Southern mode they would sit on the porch drinking buttermilk while Pop's
 daddy, who was one hundred one, tossed a shovel across his shoulder and nipped
 down through the piny woods to disinter some fruit jars of white lightning and
 outwit the Feds.  Mama said the liquor was so raw it'd take the enamel off
 your teeth.  But it must have been doing something right because the old men
 swore by it.  "We have a little toddy now and then through the day, yessiree,"
 Pop's daddy said, a Home Run cigarette dangling from his mouth.  "Good corn
 likker's the secret to long life; wouldn't miss a day."
    Pop himself had no patience for Mama's shudder as she gagged down the
 white-corn squeezings and longed for something bottled in bond.  "That gov-
 ernment whiskey?  Why, 'tain't nothing but a little water and a double handful
 of chemicals that'll kill ya surer'n hell."  Pop's professional bias notwith-
 standing, it's likely that I-some-I double handful of chemicals -- produced in-
 ternally or consumed in the course of everyday life -- enabled the Adams men
 to survive in exceptional health and vigor to great old age.
    The search for this double handful of chemicals -- a magic potion to stave
 off death and postpone the ravages of age -- is as old as man.  The myth of
 Shangri-la, for example, comes from the Greek tale of the Hyperboreans, who --
 after living 1,000 years -- simply plunged into the sea.  The promise of gold
 wasn't the Spaniards' only quest in the New World: They genuinely thought they
 would find the Fountain of Youth on the shores of Florida.  Had the Spaniards
 recognized Aztec and Inca ritual snake paintings as symbols of rebirth,
 though, it would probably have tipped them off: The Indians were looking, too.
    But now, after millennia of frustration, youth elixirs may be at hand.
 What's more, the dozen or so substances on the horizon stem not from the com-
 mercial aspirations of a health-food chain or the twisted imaginings of a
 crank but from a new and profound understanding of how we age.
    To scientists in the forefront of longevity research, aging is the tragic
 side effect of life.  The hormones released during puberty and as a result of
 stress slowly erode the body's organs.  The food we eat and the air we breathe
 generate highly reactive free radicals, which make subtle but deadly changes
 in DNA.  And environmental hazards, from ordinary sunlight to industrial
 toxins, infiltrate the cells, helping to grind their engines to a halt.  Some
 scientists have even found compelling evidence for an aging clock in the
 brain.  As that clock winds down, they say, it alters the levels of hormones
 and other biological substances, slowly lowering the effectiveness of the
 heart, lungs, immune system, and just about everything else that keeps the
 body healthy and strong.
    Increased comprehension of the problems, however, may soon yield what
 amounts to an aging cure.  Within the next decade we might use hormones to
 bolster our immune systems, viruslike vaccines to slow the death of cells, and











 uric acid to prevent the destruction of our genes.  Such supplements could
 help us maintain our health and vigor throughout much of our current maximum
 life span of 115 years.  What's more, in the twenty-first century these
 potions will be dwarfed by a new, more potent generation of "longevity pills."
 Enzyme drinks will endow us with the ability to repair each new nick in our
 armor of DNA, and synthetic neurohormones will literally reset the aging clock
 in our brains.  Instead of simply keeping us healthier longer, these new drugs
 will push the outside of the aging envelope, eventually increasing our life
 span by dozens of years.
    The first longevity drugs to reach the market I-could-I be the thymosins, a
 family of hormones produced by the thymus, the master gland of the immune
 system.  "The immune system is the bubble that protects us from a dangerous,
 hostile environment," says biochemist Allan Goldstein, chairman of the bio-
 chemistry department at George Washington University.  "And the immune systems
 of superhealthy people are unusually effective.  The thymosins play a key role
 for these people.  Our goal is to learn how.  Then we'll put the thymosins
 into stay-healthy pills, to be taken once a day like vitamin supplements.  The
 pill could add perhaps a dozen years to the maximum human life span of one
 hundred fifteen.  But even if it doesn't, it should help us live out in health
 the years to which we are genetically entitled."
    Twenty-five years ago no one even knew what the thymus gland was.  Indeed,
 because the thymus is the first gland in the body to atrophy -- it weighs 200
 to 250 grams at birth, begins to shrink at puberty, and has shriveled to a
 three-gram, grizzled clump of cells by the sixth decade of life -- scientists
 always believed it had no function at all.  But in 1961 researchers from the
 University of Minnesota removed the small, pink organ from a group of newborn
 mice.  Much to their surprise the mice failed to grow and then died of over-
 whelming infection.  The suggestion: that the thymus gland was crucial to the
 immune system I-and-I, quite apart from that, to the growth of the whole organism.
    Enter Goldstein, a brilliant young post-doctoral student at Albert Einstein
 College of Medicine in New York.  The year was 1964, and Goldstein was lucky
 enough to be working under the late biochemist Abraham White.  When asked by
 White to conduct a needle-in-a-haystack search for a thymus hormone, Goldstein
 agreed.
    The thymus and its hormones, Goldstein eventually learned, control produc-
 tion of the white blood cells known as T cells, the brain and brawn of the im-
 mune system.  He found that the thymosins work their magic by aiding in the
 activation of three types of T cells: I-killer-I cells, which attack foreign or-
 ganisms and cancer cells directly; I-helper-I cells, which aid in the production
 of antibodies; and I-suppressor-I cells, which prevent the immune system from at-
 tacking one's own tissue.  "It was obvious," Goldstein says, that "any im-
 balance in the numbers of various T cells could lead to poor health.  The fur-
 ther implication: that we could increase a person's immunological response by
 manipulating the amount of thymosins in the blood."
    Finally, in the early Seventies, Goldstein put his theories to the test
 with a five-year-old girl named Heather, who was suffering from a condition
 known as thymic hypoplasia.  "Her body didn't make enough T cells," Goldstein
 explains.  "She should have weighed sixty to seventy pounds, but she weighed
 only twenty-six pounds.  She had all sorts of severe infections.  In truth,
 her condition was terminal.  But five days after we started her on thymosin,
 her infections had decreased, and she was gaining weight."
    Today, Heather is a healthy junior high school cheerleader living a normal
 life.  "I have a beautiful picture of Heather on my wall," Goldstein says.
 "And I think that what was true for Heather will be true for the great majori-
 ty of the aged.  Right now the shriveled thymus glands of the elderly produce
 only small amounts of T cells.  Instead of suffering from the acute disease
 that Heather had, they go into gradual decline.  But for them and for Heather,
 the solution will be the same.  If we can give them enough thymosin to keep
 the T cell level high, we should be able to enhance immunity throughout old
 age."






    Rejuvenating the immune system with thymosins would add perhaps a dozen
 years to life by fighting off cancer, arthritis, pneumonia, and many other
 diseases to which the aged are prey.  But Goldstein's most recent work, sug-
 gesting that the thymosins regulate an aging clock in the brain, should
 I-revolutionize-I the longevity field.
    According to Goldstein, the idea that the thymus regulated more than the
 immune system came to him in the mid-Seventies as a result of a series of ex-
 periments done by endocrinologists like Sandra Michaels at the State Univer-
 sity of New York at Binghamton.
    Michaels found that removing the thymus gland in female mice not only
 decreased resistance to infection -- a sign of impaired immunity -- but also
 distorted the ovaries and altered the vaginal opening.  What's more, when
 Michaels gave the mice thymosin supplements, the conditions were corrected.
 Strange as it seemed, the thymosins -- in addition to the normal array of sex
 hormones -- were affecting sexual development, usually under the control of
 two glands at the base of the brain: the hypothalamus and the pituitary.
    Goldstein decided to study the relationship between sexual development and
 the thymosins, too.  Under normal circumstances, he knew, the hypothalamus
 secretes hormones that trigger a second platoon of substances in the pituitary
 -- the sex hormones -- that take us through puberty and ultimately make us ma-
 ture.
    Goldstein and Robert Rebar, now at Northwestern University Medical School,
 found that when they removed the hypothalamus and pituitary from mice and kept
 them in solution, the glands I-still-I released the full cascade of hormones -- as
 long as I-thymosin-I was added to the solution as well.  Thymosin, it seemed,
 could trigger the release of hormones in the brain.
    In subsequent experiments Goldstein learned that thymosins were directly
 linked to other brain systems as well: They could stimulate the brain's pro-
 duction of adrenocorticotrophic hormone (ACTH), normally associated with
 fight-and-flight reactions; beta endorphin, the "feel-good" chemical; and pro-
 lactin, a growth hormone.  Stimulation of ACTH, for instance, caused the
 adrenal gland to pump out the hormones of stress.  Even more interesting, he
 found, the stress hormones traveled full circle back to the thymus gland.
 They shrank the gland, turning production of thymosins -- and thus release of
 stress hormones -- down.
    According to Goldstein, these elaborate feedback loops between the thymus
 and the brain are the key to aging itself.  "As we grow older," he says,
 "there are changes in brain chemistry.  These changes alter hormone levels,
 causing deterioration throughout the body.  And our studies place the thymo-
 sins at the center of this process.  It's even possible that the whole range
 of brain hormones falls off from optimum levels as soon as the thymus begins
 to shrink, before the onset of puberty.  The suggestion is that it's the dete-
 rioration of the thymus that leads to deterioration of the brain -- and
 ultimately of the body itself.  By adding the thymosins back, much of that
 decay should be set in reverse."
    Goldstein still recalls that when he first developed an interest in the
 field of aging, his mentor, Abraham White, said, "Allan, whatever you do,
 don't pursue it until you're at least forty-five because it's sure to ruin
 your reputation.  People will think you're a crackpot."  Now forty-eight, with
 the discovery of the thymosins behind him and pictures of powerful political
 friends on his office wall, Goldstein can I-afford-I to dream: We know for sure
 that thymosins prime the levels of brain hormones involved in reproduction,
 growth, and development, he says.  Thus we should be able to use them to main-
 tain a whole complement of characteristics associated with youth: fertility,
 razor-sharp cognitive skills, facile memories, fast reflexes, potent wound-
 healing abilities, and even that most intangible of traits, a youthful zest
 for life.  Because these restorative hormones also bathe our skin, muscles,
 and bones, these body parts should retain their youthful structure and ap-
 pearance as well.
    "In five to ten years even healthy people will be taking the thymosins on a






 daily basis," Goldstein declares.  "Those supplements should help to push the
 average person's vigorous years upward of eighty or ninety simply by boosting
 the immune system.  Because we'll also increase the level of vital brain
 hormones, the impact will probably be greater still."
    While Goldstein wants to reset the aging clock in the brain with thymosins,
 other substances may also prove to be potent antiaging agents.  As it turns
 out.  It might be possible to tap into the feedback loop of aging at any point
 along the way.  And one of the most promising youth elixirs to emerge from the
 brain -- thymus feedback loop has the jawbreaking name of I-dehydro--I
 I-epiandrosterone-I, or DHEA.  One of the most common steroid substances secreted
 by the adrenal gland, DHEA has recently been shown to protect the thymus
 gland, increasing the number of T cells available to fight off infection and
 disease.
    The first chapter of the DHEA story, though, started more than a decade
 ago, when Temple University cancer researcher Arthur Schwartz stumbled upon a
 study of 5,000 women on the British island of Guernsey.  The study found that
 those women who eventually developed breast cancer had abnormally low levels
 of DHEA.  It seemed to Schwartz that if low levels of DHEA were associated
 with the presence of cancer, high levels might keep cancer away.
    Schwartz went on to add DHEA and powerful carcinogens to animal cells in
 culture.  The carcinogens alone would have resulted in high rates of mutation
 and cell death.  But with the addition of DHEA, the culture continued to grow
 in perfect health.
    To try to understand these results Schwartz went back to the literature for
 clues.  And two things stood out.  First of all, the amount of DHEA in the
 body was highest at age twenty-five of thirty.  From that point on it
 decreased until, at age seventy, it was at about 5 percent of its peak.
    Even more interesting, DHEA altered metabolism.  Excess glucose, Schwartz
 explains, is normally stored in the body in the form of fat.  But when DHEA
 was added, the fat pathway was blocked.  The glucose instead traveled down the
 only other metabolic pathway available -- the energy-yielding pathway, where
 it was converted to the body's ultimate form of fuel, ATP.  Significant weight
 loss resulted.
    Studies had long shown that low-calorie diets prevented some forms of can-
 cer.  Now it seemed as if a mysterious cancer preventative, DHEA, acted just
 like a low-calorie diet, promoting weight loss.  Perhaps DHEA and low-calorie
 diets worked in much the same way.
    If so, Schwartz knew there was a tantalizing tie-in with aging.  Thus far,
 the only proven means of extending life had been fasting: Anecdotal evidence
 came from the Himalayan Yogis, known for their long lives and subsistence
 diets.  And experimental evidence came from Cornell University nutritionist
 Clive McCay, who in 1935 doubled the average life span of rats by limiting
 their food intake.  Not only did McCay and other researchers eventually use
 the technique to stretch the average life span in a large number of mammalian
 species, the researchers also found they could increase what's known as I-max--I
 I-imum-I life span -- the age reached by the oldest survivor of a population.  The
 implication: Something basic to the very mechanism of aging had been changed.
    Schwartz set out to see if that mechanism, whatever it was, could be af-
 fected by DHEA as well.  And after eight months he achieved remarkable
 results.  Untreated mice "were coming down with cancer right and left," while
 those injected with DHEA had no tumors at all.  But the absence or presence of
 cancer was just the beginning: The untreated mice seemed old.  They couldn't
 move as quickly, and their coats were coarse and gray.  The DHEA mice ran
 around like pups -- and their coats were sleek and black.  Says Schwartz,
 "Without a doubt they were aging at a slower rate."
    Today Schwartz is working with a safer, synthetic analogue of DHEA that he
 says is ten times more potent.  He still hasn't received Food and Drug Admin-
 istration approval to test the analogue on humans, but he expects to receive
 the go-ahead in a couple of years.  And when he does, he hopes he might see
 some of the same life extension effects in people that calorie restriction has






 in the mice.  If animal results can be carried over to humans -- a distinct
 possibility -- then the DHEA analogue might extend our life spans by as much
 as 50 percent.  In other words, when treated with the supplements a sixty-
 year-old would resemble in every respect the forty-year-old of today.  At age
 one hundred the treated individual would resemble a healthy person at sixty-
 five.
    "The goal right now," Schwartz adds, "is to understand the mechanism by
 which DHEA seems to promote weight loss I-and-I longevity.  Once we understand
 what's happening during calorie restriction, which seems to be the same thing
 that's happening when DHEA is consumed, we might develop a host of DHEA-like
 substances that can help us lengthen life -- without reducing a person's
 weight."
    Many have taken Schwartz's goal to heart.  This past summer, when longevity
 researchers attended the prestigious Gordon Conference in the tiny college
 town of Plymouth, New Hampshire, the I-big-I news was that the diet-restriction
 mechanism -- and the body chemicals that drive it -- were on the verge of
 being found.
    Gathered at the foothills of White Mountain, in the solemn lecture halls of
 the Plymouth State College, the world's top longevity researchers were un-
 prepared for the weight of evidence that would mount.  First German
 gerontologist Klaus Beyruther reviewed the life cycle of a cell.  Ever since
 Leonard Hayflick published his classic paper in 1961 it has been known that
 human cells are mortal: They divide some 60 times over a period of years.
 Then they suddenly stop.  Beyruther explained that the amount of time between
 each division cycle could be increased or decreased, depending on the
 nutrients present in the petri dish.  The cells could divide at least 60 times
 in as little as a year; but if they were virtually starved, the 60 divisions
 would take three times as long.  If diet-restricted mice stretched out their
 life spans because they had less food, perhaps diet-restricted cells did the
 same.
    Also on the agenda was physiologist Edward Masoro of the University of
 Texas at San Antonio.  When Masoro restricted the calorie intake of laboratory
 rats, he extended life spans by 50 percent.
    Recently, Masoro reported, he had come to suspect that the increase in life
 span might be due not to a decrease in calories per se but rather to a
 decrease in a specific I-component-I of the diet.  To test that notion he
 restricted elements of the everyday diet, one by one.  But it was to no avail.
 He now believes that diet restriction itself seems to trigger the release of a
 neurotransmitter or hormone, and this, in turn, is what extends life.  "I'm
 now preparing experiments with two guiding principles: What kind of hormonal
 change might cause life extension?  And how can hormonal response be modified
 by calorie restriction?  Once we find the answers to these questions, we may
 be able to home in on the specific biochemical mechanism.  Then, and this is a
 very real possibility, we'll be able to intervene in that mechanism, actually
 extending life."
    The mechanism suggested by Masoro, it turns out, may have been found in
 what amounted to the most explosive life extension news in years.  Molecular
 biologists James R. Smith of Baylor Medical College in Houston and Charles K.
 Lumpkin of the Veterans Administration Medical Center in Little Rock,
 Arkansas, and their colleagues said they were zeroing in on a senescence
 protein that inhibits DNA synthesis in skin cells, literally shutting down the
 cell.
    As Lumpkin, a specialist on aging tells it, he began to suspect the exist-
 ence of such a protein when he learned that old cells, infected with certain
 viruses, seemed to revert to youth.  If those old cells were damaged in
 numerous ways, he asked himself, how could a single virus restore them to
 vitality?  It just couldn't.  "I began to think," Lumpkin says, "that the
 virus simply repressed a protein that shut down the cell."
    Then, in the early Seventies, Lumpkin discovered a paper by pathologists
 Tom Norwood and George Martin of the University of Washington in Seattle.  The






 Seattle scientists took young and old cells and I-fused-I them to produce a cell
 hybrid -- a single cell body with two nuclei in the center.  (The cell nucleus
 contains the genetic material, the DNA.)  In that single cell, neither the old
 nucleus nor the young nucleus was able to synthesize DNA.  In other words, the
 fused cell took on the characteristics of the old cell.  The implication: The
 old nucleus produces a protein that shut down its own replicative machinery
 and then traveled through the cell body to squelch the young nucleus as well.
    Lumpkin was so impressed by the work that he went to Seattle to study with
 Martin.  And it wasn't long before he'd used Martin's findings to help develop
 a potent theory of his own.  Working with molecular biologist Jim Smith, Lump-
 kin proposed the existence of one or more cell proteins that turned DNA
 synthesis off.
    Last year the two tested their notion in the lab.  In essence they ex-
 tracted genetic material from old cells, divided that material into segments,
 and injected each segment into a different young cell.  Time after time, a
 specific bit of material from the old cell made the young cell age as well.
    The present goal is to isolate and clone this genetic material -- apparent-
 ly the gene that codes for the senescence protein.  Once the gene is found,
 Lumpkin says, we can find ways to turn it off.  One suggestion might be a vac-
 cine that instructs the body to produce antibodies against the protein.  An-
 other solution would be to override the protein with another natural substance
 -- one that turns the cells on.
    That may soon be possible, thanks to biochemist Vincent Cristofalo of the
 University of Pennsylvania and the Wistar Institute in Philadelphia.
 Cristofalo and his group have found proteins in the membrane that revive
 senescent cells.  "There's a definite relationship,"  Cristofalo says,
 "between the balance of cell proteins and the rate at which organisms age."
    As we get older, he explains, the proteins that prevent DNA synthesis be-
 come increasingly common in a larger proportion of our cells.  As a result
 cells become less able to respond.  Muscles, for instance, contract more slow-
 ly.  And the cell receptors, which normally act as portals for everything from
 energy molecules to growth hormones, don't always recognize the substances
 they were designed to process and absorb.  Without growth hormones, for exam-
 ple, wounds won't heal.  And without sufficient energy the body can't function
 at all.
    There's a strong correlation, Lumpkin says, between the life span of cells
 and the life span of the organism.  "On the most basic level," he says, "the
 eighty-year-old would be able to heal his wounds as easily as if he were fif-
 teen.  Theoretically speaking, if we were to suppress the protein that in-
 hibits DNA synthesis, our cells should be rendered immortal."
    If all the body's organs, including the kidney and the liver, age in
 analogous ways, he adds, we might be able to surpass the current limit of one
 hundred and fifteen years in a sexually mature but youthful state, our bodies
 tight and our minds alert.  "Once we understand the cellular pathways," Lump-
 kin says, "we might even be able to live three or four hundred years and keep
 on going from there."
    Listening to the findings, gerontologist Richard Cutler of Baltimore's
 Gerontology Research Center suggested that the on/off proteins found by Smith,
 Lumpkin, and Cristofalo were the very substances responsible for extending the
 lives of lab mice placed on restricted diets.  Mulling it over while in a
 canoe on Plymouth's placid Lake Squam, Cutler was reminded of a well-
 understood phenomenon known as heat shock response.  "When heat becomes parti-
 cularly intense, neurotransmitters in the brain stimulate a set of genes to
 produce a protective protein," he explains.  "The protein literally cools the
 animal down, eliminating undue stress."
    Dietary restriction might work the same way.  When the food supply is low,
 he notes, adult animals can't sustain a fetus or care for their young.  In the
 face of this threat a hormone like the one suggested by Masoro probably
 switches on a special gene.  The gene, in turn, probably generates the senes-
 cence protein found by Lumpkin and Smith.  Under normal circumstances that






 protein would be produced only by very old cells, to trigger death.  But in
 times of famine they might be switched on temporarily, delaying development --
 and the years of reproductive viability -- until such time as nutrients would
 again abound.  When food becomes plentiful, the protein found by Cristofalo
 comes into play.  "Once we isolate the neurotransmitter or the proteins," says
 Cutler, "we might use them to enjoy the same antiaging benefits of diet
 restriction we see in the mouse."
    A serum that inhibits the senescence protein might drastically increase the
 longevity of our cells, conferring infinitely more staying power on our organs
 and the body as a whole.  But according to Cutler, the technique will add
 decades to life only if supplemented by a I-third-I sort of potion -- one that
 prevents genetic damage caused by metabolism, environmental toxins, and the
 sun.
    In the forefront of that research is the short, stiletto-thin Bruce Ames.
 A biochemist at the University of California at Berkeley, Ames is the con-
 troversial researcher who first declared that small amounts of man-made chemi-
 cals cause cancer by creating mutations in our genes.
    In 1984, just as people were embracing the notion that cancer is caused by
 the toxins of our industrialized world, Ames came out with an even more radi-
 cal sentiment.  True, man-made chemicals are carcinogenic, he said.  But most
 cancer-causing mutations come from the very food that we eat and the air that
 we breathe.  Living is like being irradiated, he explained.  Many fruits and
 vegetables produce natural pesticides that are as mutagenic as man-made ones.
 And the oxygen molecules we breathe tend to turn into highly reactive free
 radicals -- particles that scavenge the body, voraciously consuming bits of
 DNA and damaging the cells.
    As far as Ames was concerned, these same forces were responsible for aging.
 The genetic damage they caused was fairly constant throughout life, he
 theorized.  Although DNA was always repairing itself, eventually the mutations
 would mount, resulting in aging and death.
    He found support for his ideas in evolution itself.  Indeed, as we evolved
 from our early primate ancestors to I-Homo sapiens-I, over a period of millions of
 years, our life span basically doubled while our metabolic rate was cut in
 half.  "Perhaps we lived twice as long," Ames suggests, "because we were
 producing free radicals and other natural toxins at half the rate."
    Ames was also aware of new research showing we could protect ourselves
 against the oxygen scavengers, at least to a degree, with another sort of nat-
 ural substance -- the I-anti-Ioxidants.  This group -- including vitamin E, selen-
 ium, beta carotene (which provides carrots with their orange color), and su-
 peroxide dismutase -- literally neutralized the free radicals before they had
 a chance to destroy DNA.  "A major factor in the evolution of increasing life
 span," Ames adds, "might well be an increase in the presence of these pro-
 tective mechanisms against free radicals."
    Fascinated by this theory, Ames even discovered another, unlikely anti-
 oxidant -- uric acid, long considered nothing but a waste product.  "I real-
 ized that at the beginning of primate evolution, we'd lost the enzyme that
 breaks down uric acid.  What's more, the kidneys pump ninety-five percent of
 all uric acid back into our blood," he says.  Thus unlike mice and rats, we
 have high levels of uric circulating throughout our bodies.
    If antioxidants like uric acid and superoxide dismutase propelled the
 evolution of human longevity, then it only makes sense that raising their
 levels would extend life span even further.  The problem with taking such sup-
 plements in pill form, however, is that increasing one antioxidant reduces the
 levels of all other antioxidants -- unless the I-total-I antioxidant load is espe-
 cially low.
    If that load is low, DNA damage might pile up more rapidly than normal, and
 life span would be short.  But if we could somehow I-detect-I that damage early in
 life, we would be able to I-increase-I antioxidant protection.  DNA damage would
 be limited, and the potential for a normal life span would be restored.
    Already Richard Cutler is developing a longevity kit to do just that.






 First he screens patients for high levels of thymidine glycol, a by-product of
 damaged DNA.  "If someone excretes excessive amounts of thymidine glycol in
 the urine," Cutler says, "it's probable that free-radical damage is high --
 and that the antioxidant level is low.  We'll keep adding different
 antioxidant supplements and retesting the urine for thymidine glycol.  When
 the right combination of supplements has been found, thymidine glycol should
 be reduced to normal.  Then we'll know that the aging is as low as possible
 and that antioxidant protection is prime."
    Cutler, who takes supplements of beta carotene and vitamin E himself, says
 that his current technique may help those who now age abnormally quickly.  But
 for the rest of us other tactics may be suitable.  "What we've got to do is
 understand how evolution increased our antioxidant level, then use the same
 technique ourselves."
    One of evolution's tricks may have been convincing the cells that extreme
 genetic damage had occurred.  He explains: "When you exercise, you burn more
 oxygen, produce more free radicals, and also generate more antioxidant pro-
 tection.  If you could trick the cells into thinking that exercise or its
 equivalent was taking place when it wasn't, then you might I-increase-I the
 antioxidant levels while free-radical damage stayed the same."
    Cutler is currently working on two ways to trick the cells so that excess
 antioxidant production occurs.  In one experiment he's simply injecting mice
 with thymidine dimers, chemical by-products of damaged DNA.  In another he's
 injecting them with cyclic GMP, a messenger chemical produced whenever free-
 radical damage has occurred.  So far, he says, the cyclic GMP and the dimers
 seem to be ringing the alarm: Treated mice are more resistant to radiation.
 The extra protection, he adds, can be easily explained if we assume that ex-
 cess antioxidants are produced.
    If that turns out to be the case, Cutler says, then such supplements as
 thymidine dimers or cyclic GMP might eventually increase our protection
 against free radicals, expanding our maximum life span as much as a decade or
 two.  But in the distant future there will be a far more powerful way of
 fighting off DNA damage -- increasing the amount of enzyme available to
 literally I-repair-I our genes.  Working on this technique is cell biologist and
 paramecia expert Joan Smith-Sonneborn of the University of Wyoming at Laramie.
 Someday, Smith-Sonneborn believes, "we'll be able to identify and clone the
 genes that make the different repair enzymes and transfer them into our
 cells."
    Right now Smith-Sonneborn is attempting just that with her paramecia.
 She's chopping the paramecia's genome into sections and matching each section
 with a I-known-I repair gene from yeast.  When she gets a match she'll know that
 the paramecia's repair gene has been found.  Then she'll transfer cloned ver-
 sions of the gene into the paramecia cells.  "If the repair genes do what we
 think they should," she says, "the life span of the paramecia will increase."
 We might then use the same technique to create a gene-repair formula for con-
 sumption by man.
    Yet another formula might pry open our genes, Smith-Sonneborn believes.
 DNA, she explains, is tightly coiled.  If we could relax the coils, the genes
 would open up, and we'd get in more repair enzyme.
    One of the most important benefits, Smith-Sonneborn predicts, would be a
 boost for our immune system: Recent experiments lead her to suggest that some
 DNA-repair enzymes and the antibody-building enzymes may be one and the same.
 And, she adds, it's possible that an increase in these enzymes will offer a
 cosmetic advantage, too.
    "Skin is wrinkled by ultraviolet rays from the sun," she explains.  "What
 those rays do is damage DNA.  But repair enzymes might fix the damage as fast
 as it occurs."
    Finally, Smith-Sonneborn's experiments indicate that stimulating DNA repair
 can boost the life span of single-celled paramecia by 50 percent.  "One
 thing's for sure.  When we tap into the mechanism of DNA repair, we're tapping
 into a great many of the things that make us age," she says.  "If we can in-






 crease repair, we'll help ameliorate any pathology associated with damage to
 our genes."  Our immune systems should produce more antibodies, and we should
 be less prone to cancer and infectious diseases.  We'll reach old age later,
 and we might be able to greatly exceed the maximum human life span of one hun-
 dred and fifteen years.
    Many experts, of course, doubt that we'll be able to achieve drastic expan-
 sion of human life any time soon.  Dr. Edward Schneider, deputy director of
 the National Institute on Aging, says, "I don't foresee a magic bullet, an
 antiaging pill that you could take to restore youth.  But I do predict that
 our increased knowledge about the aging of different organs will enable us to
 prevent various body functions from deteriorating.  We might be able to re-
 store immune function, for instance, and even prevent short-term memory loss.
 In the next decade or so, we might see average life span increase from
 seventy-five to about eighty-five years for men and ninety years for women.
 Perhaps in the next few years someone will eventually live to be as old as one
 hundred and thirty.  Barring some unforeseen breakthrough, though, I don't
 think we'll see people living to one hundred fifty in the near future."
    But a lot of longevity researchers say Schneider may be erring on the side
 of caution.  "There's no obvious bottleneck on the extension of life span,"
 Cutler declares.  "Today it seems probable that aging is caused by hormones
 and other molecules that alter the activity of genes.  We should eventually be
 able to manipulate those hormones and molecules directly or through control
 sites in the brain.  The result would be a slowing of the aging rate of vir-
 tually every organ and cell."
    The impact would be profound.  Once we fine-tune our engines we'll spend
 more time in the flush and energy of youth.  Natural proteins will make us
 more vigorous.  Enzyme supplements will restore smoothness to our skin and
 rigor to our bones.  Hormone additives will add fight to our immune system,
 giving us powerful resistance to cancer, arthritis, lupus, and the array of
 infectious diseases.  Viruslike vaccines will literally alter our genes, sup-
 pressing the chemicals that once wore us down and made us old.
    After we extract the secret fuel of old Pop Adams and his hundred-year-old
 daddy, we'll fulfill the dreams of Ponce de Len.  In the twenty-first century
 the Fountain of Youth will be here.  In one sense, Ponce de Len was born 500
 years before his time.  But in another, the answers have always resided within
 him and us all.