You Don't Look a Day Over 150. Want to Screw?

One enduring certainty of medical science has been that the maximum human life span is, give or take a few birthdays, 120 years. There is now a growing feeling that the new human biological limit could be 150--or even 200-- and that with the right treatments just about anyone will be able to live that long.

"Now it's a function of money," says Michael Rose, professor of evolutionary biology at the University of California-Irvine and a pioneer in the field of delaying aging. "The basic scientific questions have mostly been resolved, and we're just waiting to turn the crank. It's breath-taking what can be done now."

"The spirit of Ponce de León lives on," MIT's Leonard Guarente wrote in an academic journal. Guarente is another pioneer in research to make youth last longer--and to postpone the infirmities of old age. "The idea is to maximize a healthy life span of 120 years," says Dr. Michael Fossel, editor-in-chief of the Journal of Anti-Aging Medicine. "If people can hang on another 20 years, I'm sure it'll turn out to be a realistic goal."

The science behind these developments is complex, but think of a clock built into our genetic makeup steadily ticking away. When your clock, or your collection of clocks, has run the course dictated by your genes, you're dead. Now, thanks to break-throughs in genetic research, doctors believe they can slow down or even reset those clocks--and reset them again and again. At midnight, or bedtime, as it were, the genetically altered man of the future will be as fresh as he was at 10 A.M.

Seymour Benzer of the California Institute of Technology put it some what differently when talking to Time magazine: "Perhaps aging can be better described not as a clock but as a scenario, which we can hope to edit."

Hyperlongevity research is advancing with startling speed. If you're 20 years old now, there is every reason to believe you can live a much longer time than your genes originally had in mind for you. "Many people alive today will live into the 22nd century," said Dr. Roy Walford of the UCLA School of Medicine. "I can predict that with some certainty."

The most optimistic--if that's the word--prognosticators say that in 20 years, newborns will routinely have life expectancies of 1 50 or 200--if, of course, they avail themselves of the various treatments and procedures that are now being developed.

One day all the tributaries of research may produce a modern version of the Fountain of Youth--the longevity pill.

"There's nothing bigger," Steven Austad, professor of zoology at the University of Idaho, told The New York Times about stretching the human life span. "If we could do it, there's nothing bigger."

The quest for hyperlongevity may well become one of the most expensive, glamorous and problematic enterprises of the 21st century. It already has its share of legends, eccentric heroes, financial disasters, moral conundrums and striking possibilities. On these pages are glimpses from the cutting edge, along with what you need to know to survive one of the most exciting episodes in medical history.

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From Alchemy to the Cutting Edge

We owe all these possibilities to scientists who endured the mockery of their colleagues when their work was regarded as akin to alchemy. After all, in terms of evolution there is no point in longevity, and until recently, our genes, cells and chromosomes seemed too complicated to tamper with. Two decades ago, research of the sort now booming was, in the eyes of mainstream medicine, the province of charlatans, fringe scientists and fast-buck artists. "We weren't even pariahs," says Michael Rose, an early maverick. "We were flies buzzing around the pariahs' faces." Back then, aging was, Rose noted in The New York Times, "famous as the rock on which scientists dashed their careers."

Speaking of Flies, Can a Man Make Love for Three Weeks Without Stopping?

It was Rose who made a break-through discovery--with the help of fruit flies who lived, served science and died in his laboratories, eating mushed bananas, sucrose and Jell-O pudding while they engaged in elaborate precoital rituals.

Until Rose came along, fruit flies typically began to reproduce when they were 14 days old and died around 40 days. But some flies lived longer--some as long as 70 days (in human life span, well over 100 years). Rose hatched the eggs of those oldest but obviously fit flies, encouraged the new flies to reproduce, then repeated the experiment over two decades on hundreds of generations of flies. Rose's superflies lived an average life of 90 days--or about 160 years.

The experiments proved, Rose says, that aging is not an absolute. In theory, at least, it means that humans could get where flies had gone. "My flies are athletically superior, they have a greater ability to do work and a greater ability to survive under stress," Rose noted in The New York Times.

And, he adds, they have sustained copulation (after the male flies make their wings hum, and examine and lick the females' genitalia) for 20 minutes (three weeks in human terms) and can copulate 10 to 12 times in 24 hours.

If Flies Can Do It...

What are the implications for you and me? Listen to Rose: His flies, he declares, "had sex more often and more frequently at age 120 than ever. We're not talking about producing the kind of guy who goes to a monastery to lead a contemplative life. We're talking about a 110-year-old playing tennis." It's as if, says Rose, his flies had said, "Screw it! Life is a party and we are going to do it more frequently and for a longer period of time than ever before."

Sexy at 90? Are You Sure?

Cynthia Kenyon, professor of biochemistry and biophysics at the University of California--San Francisco, is another early believer who has been vindicated. Her experimental subjects are nematodes, worms no bigger than commas--creatures that have some of the same basic biological processes as humans and which have many genes similar to those found in humans.

In the Nineties Kenyon identified the gene that controlled the worms' aging clocks and was able to tweak it, as it were, to the "off" position. The worms simply stopped (or at least paused) aging.

Eventually, Kenyon's colleagues produced worms that lived as long as six times longer than the two weeks that had been considered the normal life span. "Normal" worms become unpleasant sights well before they die, but even at advanced ages genetically altered worms have smooth skin and move with smooth undulations. "The idea that I could look like this at 90 is not so far-fetched," says 46-year-old Kenyon. "The lights are green everywhere you go."

Unsung Role Models

Jeanne Calment, a Frenchwoman who met Vincent van Gogh in 1888 when she was 13, was 122 years old when she died three years ago. There is no proof that anyone has ever lived longer, but medical researchers seem to be ignoring the lessons of her life. The evidence is that she lived well. She ate plenty of olive oil, drank port, smoked cigarettes until she was 117 and ate as much as two pounds of chocolate every week. And she was not the sort of person to be easily impressed. She found Van Gogh, for example, "very ugly, ungracious, impolite, sick. They called him loco."

Sarah Clark Knauss of Allentown, Pennsylvania died last year at 119. She had avoided vegetables and favored potato chips, chocolate and pretzels.

As a Matter of Fact

There are already some 135,000 people around the world who are 100 years old or older. There are some 62,000 in the U.S. A century ago there were an estimated 3500. According to United Nations statistics, there are nearly two women for every man over 80 around the world. Over 100, the ratio is four women for every man. Thomas Perls, director of the New England Centenarian Study at Harvard Medical School and Beth Israel Deaconess Medical Center, reports that men who live into their 90s, by the way, tend to hold on to their mental functions better than women who live into their 90s.

A Pretty Thought

WHY DIE? was the headline on a January 1, 2000 column in The New York Times in which William Safire said: "For future people, doddering will no longer be an option. Throw out those second-millennium images of codgers in wheelchairs staring at the wall. The Gramps of a century or so from now will be swiveling on the dance floor with his replacement hips and fresh lungs and newly enlivened brain and pocketful of potency pills."

A Less Pretty Thought

Remember telomeres? The idea is to fiddle around with them genetically so that your cells keep on dividing and you'll never have to worry about sagging skin again.

Only cancer.

If we genetically engineer the perpetual division of our healthy cells, no one can be sure it would not trigger the mechanism that allows cancerous cells to proliferate. "That's why we have to think hard about taking the steps to postpone aging," says Judith Campisi, the telomere expert at the Berkeley lab. "It's just not that simple."

Two Paths to Long Life You Should Probably Skip

Reducing caloric intake toward starvation levels increases the chances for longer life--according to experiments on flies, protozoa and rodents.

Castration is a surefire way to extend life span--according to a variety of studies of eunuchs (and salmon).

Genes Are Very Mysterious--Or Tomorrow's Freak Shows

It's fair to say that some of the research going on evokes those science fiction films in which something goes very wrong just when the pariah scientist is on the verge of a great step forward. Is there one Big Clock in us that will be tipped off balance by genetic manipulation? Will longevity also mean people will look as if they have stepped out of a fun Picasso painting, perhaps with super-sensitive olfactory abilities and high-pitched voices? Stories have already emanated from real-life laboratories about dogs with ears growing from their spines and frogs sprouting (useless) wings that show what genetic engineering can bring about.

A Different Kind of In-Law Problem

"A 25-year-old of the future might find himself at a family reunion with his two parents, four grandparents, eight great-grandparents, 16 great-great-grandparents, 32 great-great-great-grandparents and 64 great-great-great-great-grandparents, all making fun of that doddering old wacko, 206-year-old great-great-great-great-great-Aunt Maude, who, for the 48th straight year, has dropped her century-old dentures into the coleslaw."--Seth Kugel, Satirizing Hyper-Longevity Research, in the New York Daily News, March 27, 1999

The Singapore Solution

In Singapore, there has been talk of legislation that would give each married person between 35 and 60 with children two votes and every retiree one vote.

Undertakers Have Feelings, Too

According to L. William Heiligbrodt, former president of Service Corp. International, a multinational funeral home conglomerate, "Declining death rates pose a challenge for the industry."

"Here at the funeral home I operate in middle America," Thomas Lynch wrote in a New York Times op-ed piece (March 14, 1999), "our favorite parlor game is Demographics and Expectancies. It bears a semblance to Trivial Pursuit. In the last century, the life span of Americans rose to 76 years from 47. Such wonders can be credited to antibiotics, indoor plumbing, spandex and the soybean. With the extra three decades in most of our lives, we neither cured the common cold nor secured peace in the Balkans, but we did invent the Wonder-bra and no-load mutual funds."

Human Wisdom?

"Hyperlongevity is going to be hard for us to deal with," warns Dr. Gregory Stock, director of the program on medicine, technology and science at the UCLA School of Medicine. "It puts a distance between ourselves and our history." In Dr. Stock's view, "wisdom on how to live a life" will be irrelevant.

Let's be Precise

"I don't want to achieve immortality through my work. I want to achieve it through not dying."--Woody Allen

Huxley Deserves a Medal

"Now--such is progress--the old men work, the old men copulate, the old men have no time, no leisure from pleasure, not a moment to sit down and think."--A World Controller in Aldous Huxley's Brave New World, In which people who are 60 behave as if they were 17.

How to Get Started Now

The research that may one day produce a longevity pill has already helped create products that seem to stall the aging process--at least in small, often cosmetic ways.

For example, melatonin, estrogen and testosterone are hormones that decline with age--so it seems like a good idea to replenish them. Similarly, levels of dehydroepian-drosterone, a relatively weak male hormone, start to diminish when you reach the age of 30. Low levels of DHEA seem to reduce the immune system's ability to fight disease and are associated with age-related ailments, including heart disease and cancer. Replenishing these and other hormones appears to slow aging and--despite a lack of clinical proof--helps account for billions of dollars in sales of a variety of products (treating everything from wrinkles to diminished energy) that contain them.

The human growth hormone, produced by the pituitary gland, strengthens bones and muscles. Regular booster shots, at a cost of $15,000 a year, are rumored to be the practice of many Hollywood stars, who are reluctant to talk about them. By now we all know that martinis a la James Bond--shaken, not stirred--contain antioxidants that help cells resist wear and tear. If you have any doubt, just check out the report in the "British Medical Journal" by a team of researchers at the University of Western Ontario. They said shaken martinis have double the antioxidant punch of martinis that are stirred.

How to Reset Your Clock

Telomeres are the cap ends of our chromosomes. Many human cells constantly divide, and as they do, the telomeres grow shorter. Cells stop dividing when telomeres become too short; this phenomenon may cause various troubles associated with aging. "Maybe that's why our limbs move slowly and our skin wrinkles as we age," explained Judith Campisi, senior staff scientist in the department of cell and molecular biology at the Berkeley National Laboratory and a specialist in telomeres.

Can genetic engineering step into the process and keep telomeres intact as they are in youth, creating cells that continue to divide-- and thus sustain growth? Some researchers hope that in the not very distant future, regular injections of a substance called telomerase can do just that (especially for cells in the eyes, skin and stomach lining). If all goes as planned, the cells will then renew themselves and stay young in every practical sense of the term.

The Physical of the Future

Once the human genome is fully mapped, doctors will probably be able to perform routine physicals by gene scan. The test will amount to something like genetic fortune-telling: Doctors can figure out what hidden dangers may lurk down the road. Doctors believe this kind of diagnosis will enable them to thwart, avert or at least delay some formidable killers. Of course, early detection has its downside. Imagine if an insurance company were alerted to a disposition to, say, cancer. Knowledge can cost an arm and a leg.

How to Regenerate Your Body

Doctors may soon use stem cells--potent cells from which brain, muscle and nerve cells form--to grow skin for burn victims and to make bone marrow for cancer patients. Researchers are not all that far from pushing those techniques to grow new brain and heart tissue-- and other organs as well. That means you someday could get a sort of bionic tune-up--brand-new lungs and liver-- and forget about the ravages of a lifetime of smoking and drinking.

Or what about a neuro-upgrade--your neurons tuned with those amazing stem cells--for snappier brain functions and funnier jokes? Neurobiologists have already targeted genes in mice, planning a rejiggering of their genetic makeup that would allow them to learn faster and retain information longer.

"We're just waiting to turn the crank. It's breath-taking what can be done now."

These Genes Mean Business

"These genes will be a gold mine once they are all understood, both in terms of basic science and practical sense," says Judith Campisi of the Berkeley National Laboratory. Gold mine, indeed. If you discovered or helped discover the Fountain of Youth, how much do you think your efforts would be worth?

Heavy investment in hyperlongevity is relatively new. Larry Ellison of Oracle was an early casualty, burning through big bucks with Aeiveos Sciences Croup, a firm dedicated to ending aging. It lasted less than three years, dying in 1997. Ellison established the Ellison Medical Foundation in Bethesda, Maryland, which spends close to $20 million a year researching the basis of aging.

Jouvence (now known as Health Span Sciences) was another company that set out to locate the gene or genes that control aging. Between 1995 and 1998 it spent about $2 million on gene research before shifting its focus to manufacturing antiaging nutraceutical products.

"It's very difficult to survive as an aging-research business," says one industry executive whose company burned up money doing research and collecting tissue samples. To remain viable, the company changed course and now sells pharmaceutical companies access to its library of tissue samples.

Geron Corp. of Menlo Park, California is indicative of the potential of what is happening in laboratories now. Geron, a firm with $64 million in assets and copious research archives, recently purchased Roslin Bio-Med, the firm that cloned Dolly the sheep and helped establish that cloning a human is theoretically possible. Now the two companies are working to develop perpetually dividing cells--that is, immortality.

If all goes as planned, the industry will probably create billionaires--and paupers. Right now, there is one American 65 or older for every three workers. In 30 years, even if nothing happens in longevity laboratories, that ratio will increase to one retiree for every two workers. If and when the Fountain of Youth begins to flow, those numbers will look economically healthy. Meanwhile, Peter Peterson reports in "Gray Dawn" that the "benefit outlays for just five programs--Social Security, Medicare, Medicaid and federal civilian and military pensions--will exceed total federal revenues by the year 2030."

Will pharmaceutical companies and medical providers give away the Fountain of Youth? Don't bet on it It's far more likely that hyperlongevity will be only for the rich, for a long time. The chances of a black market-- with something like immortality at stake--are obvious to young and old alike.