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Noel Thomas Patton was 50 when he decided that he would not go gently into that good night. He was born in December, 1945, on the eve of the baby boom, and sees it as his birthright not to follow in the orthopedic footsteps of his father's generation - "when you sat in your rocking chair, played checkers, watched TV and then you died." Mr. Patton, now 63, wants to keep his mind sharp and play tennis, ski and disco dance for at least another decade. "I do like discoing," he says. He believes a long, robust life is entirely possible if you can keep all your parts running smoothly. Mr. Patton knows parts - mostly mechanical ones: blowers, motors, belts and blades. The American entrepreneur made his fortune in electric fans and heating supplies. But since selling that business in 1995, the same year he first "started to feel a little stiffness here and there," he has applied his acumen to body parts - specifically the human cell. Mr. Patton believes that he has found a way to keep cells hustling well past their prime. For the past 18 months, he has been dosing himself with an extract of the astragalus plant, an ancient Chinese herb said to protect cells against the wear of time. He has also been selling the treatment - to the tune of $25,000 a year - and says many of his clients are doctors and scientists themselves. There is not yet any real proof that it works, but if it does, it would be a big deal: Extend the lifespan of a healthy cell and, perhaps, you extend the span of a healthy life. Through history, legions have hunted that prize in the waters of Babylon, in the beds of young virgins and in the fabled powers of monkey testicles. Walt Disney and baseball great Ted Williams hoped it would be found while they waited on ice. Ponce de Léon thought he'd find it bubbling up from the ground in Florida. And now Mr. Patton, a multimillionaire hungry for science to back up his hopes, has joined the age-old quest to extend the vigour of youth. His timing couldn't be better. Once considered a fringe field littered with charlatans and quacks, anti-aging research has entered its prime. Respected scientists are pursuing regenerative medicine through stem cells, searching for clues to longevity in the genes of fruit flies, flat worms and really old men and women. Dozens of legitimate companies are developing anti-aging drugs. Bruce Ames, one of the world's most-cited researchers and a winner of the U.S. National Medal of Science, has launched a company called Juvenon. None of it has yielded any proven clock-stopping treatments so far. But just as baby boomers brought the rise of disposable diapers, draft dodging, miniskirts, minivans and stock options, their march toward mortality is now making aging research a global priority. In part, it's because scientists are aging themselves. But governments too are anxious about the burden of caring for a degenerating generation. The number of people aged 80 and older is projected to quadruple to almost 400 million worldwide by 2050. The research boom is "something of an apocalyptic response to the demographic realities," says Anne Martin-Matthews, scientific director of the Institute of Aging, part of the Canadian Institutes of Health Research (CIHR). "The goal is to identify the factors that will enhance the good health of the population so that we don't exhaust our health resources." Aging research has gained such prominence that it has begun to spawn its own language - as "geroscience" strives to understand the "wellderly" and increase human "health span." In Europe, a massive, five-year effort is under way to study the genes of nearly 2,700 siblings older than the age of 90 from 11 countries. The U.S. has a Well Elderly study to investigate the links between physical activity and a healthy aging population. And next year in Canada, 160 investigators from several universities will launch the Canadian Longitudinal Study on Aging, which will follow 50,000 men and women 45 to 85 years old for at least two decades, probing the subjects' biological, psychological, social and economic changes over time. It is being billed as the most comprehensive aging study ever undertaken. The CIHR, Canada's main medical-research funding body, spent $136-million on all age-related research in the past year, more than five times what it spent in 2000-2001. The Institute of Aging now gets roughly 14 per cent of CIHR's total budget, compared to 6 per cent nine years ago. Progress has been so rapid that many researchers now see aging as a series of degenerative diseases than can be delayed or even prevented. The prospect has even sparked serious debate about the limits of the human lifespan, with a bold few predicting that the average North American girl born today will live to be 100. "We have all the tools - we understand genes, metabolism, and these things are much easier [now]to measure and manipulate," the California-based Dr. Ames says. "I think we can push back all the degenerative diseases of aging. I think we can add a few years to everyone's life." Funding fuelled In Canada, the CIHR helped to kick-start the process in 2001 when it put out a call for aging-research proposals. Angela Brooks-Wilson, a senior scientist at the B.C. Cancer Agency in Vancouver, was researching genetic susceptibilities to cancer, but she realized that she could tweak her project to qualify for the new funds. "It shows how granting agencies can foster research in a particular area," she says, adding, jokingly, "People at the granting agencies are aging too." She broadened her planned study of elderly people who were free of cancer and decided to analyze the genes of seniors who had not developed any major disease. Dr. Brooks-Wilson says human lifespan depends largely on environmental and lifestyle factors, but estimates genes account for about 30 per cent of the question. By the end of 2002, the CIHR had granted her $1.25-million over five years to study such a cohort of "super seniors." These 550 people from the greater Vancouver area, selected with information from the B.C. Ministry of Health, range in age from 85 to 105 and have never developed cancer, pulmonary disease, Alzheimer's, diabetes or cardiovascular disease. Two-thirds of them are women (who tend to live longer than men) such as Barbara Roberts, who lives alone in the city's east end and still shovels her own snow at the age of 90. "She's amazing, energetic," says Dr. Brooks-Wilson. "A live wire." Among the super seniors, researchers are looking at 25 different genes involved in metabolism and tumour suppression. They are comparing them with DNA from a control group of 550 randomly selected men and women between the ages of 40 and 50 - two-thirds of whom, statistics suggest, will not live to be 85. They are investigating whether the super seniors carry a common genetic trait that most of the control group does not. Results are expected early this year. Meanwhile, the B.C. group has already found something of interest in the telomeres of the super seniors. Telomeres are one of the hottest molecules in medicine. Like plastic caps on the ends of shoelaces, telomeres are tails at the ends of chromosomes that keep genetic information from "fraying." But telomeres are also biological time bombs: They grow shorter each time a cell a divides; and the longer we live, the more each cell has divided. The telomeres, which are actually a certain repeated sequence of DNA (TTAGGG), eventually wear down to unstable nubs. At that point, cells start to break down and die - and so, it seems, bones thin, chins sag and cancers sprout. Naturally, there's a big interest in finding ways to turn back the telomere clock. As a group the super seniors do not have especially long telomeres, says Dr. Brooks-Wilson, but their telomeres do seem to be of a generally uniform length, while the middle-aged control group shows much greater variation. The theory is that if a telomere is too long, the cell will divide more times than it should, increasing the risk of cancer. But if a telomere is too short, the cell could suffer early genetic damage, also leading to disease. In a paper published in November, Dr. Brooks-Wilson and telomere expert Peter Lansdorp speculate that the super seniors may carry an "optimal length" of telomere that "could contribute to disease resistance and promote healthy aging." Immortal cells Mr. Patton had never heard of telomeres until he attended a black-tie dinner to raise funds for aging research in Palm Desert, Calif., in 1999. By then, he had spent about four years searching for a doctor to provide him "with some decent anti-aging care." But for the most part, he said, he encountered hucksters. Then he listened to Jerry Shay, a noted cell biologist from the University of Texas Southwestern Medical Center, give a talk on telomeres. Dr. Shay, whose research helped produce the telomere theory of aging, described how activating an enzyme known as a telomerase "might be able to extend the lifespan of telomeres and immortalize cells." Telomerase is usually turned off in normal cells. But the gene that produces it is usually turned on in stem cells and cancer cells - both of which are theoretically "immortal," having the ability to multiply indefinitely. Mr. Patton immediately approached Dr. Shay, who told him that the University of Texas had licensed its telomere work to the California-based Geron Corp., an influential biotech firm that co-discovered the telomerase gene in 1997 and backed the early work on human stem cells. The next morning, Mr. Patton called Geron's CEO and made a major investment in the company. He learned that it was hunting for a compound to boost telomerase and had started talks with researchers at the University of Science and Technology in Hong Kong to look into compounds from China. As it happened, Mr. Patton was also based in Hong Kong, where he had moved with his wife, Eve, and their two children in 1987 after deciding to manufacture some of his fan and heater parts in mainland China. From there, he was able to help facilitate an agreement with the Hong Kong scientists to test 50 compounds from traditional Chinese medicine. One candidate was astragalus, a spiky shrub from Inner Mongolia that the Chinese have used for thousands of years as an immune-system booster, blood-pressure controller and overall wellness agent. They add it to stews and soups and boil it as a tea. Health-food stores carry extracts. When it was tested, according to Mr. Patton, the scientists found that the plant did indeed boost the human cell's telomerase activity. At the time, however, developing an astragalus drug was not a priority for Geron, which was concentrating its efforts on cancer and stem cells. Mr. Patton didn't want to wait. In 2002, he formed his own company, TA Sciences, in Manhattan (where he now lives part-time). He struck a deal with Geron for a worldwide licence on an astragalus plant extract for non-drug purposes. By billing his planned product as an dietary supplement and making no disease-curing claims, he could develop his alternative medicine free of the time-consuming regulatory processes of the U.S. Food and Drug Administration. Smoggy cells Bruce Ames never set out to study aging at all, let alone form a company selling an anti-aging product. The 80-year-old biochemist with the University of California at Berkeley and the Children's Hospital Oakland Research Institute has spent most of his lauded career studying DNA damage. In the 1960s, he invented the Ames test, still the gold standard in identifying cancer-causing substances. But as he became more interested in pinpointing the causes of cancer, he found himself thinking about aging. "It's clear that cancer is a disease of the aged," he says. "About a third of us have it by the time we're 80." Much of the damage is self-inflicted, he notes. Seventh Day Adventists, who don't smoke, drink or eat meat, have half the cancer-mortality rate and live about two years longer. (Asked what does eventually kill them, he jokes, "Boredom.") His research eventually focused on fighting some of the causes of aging, namely the disturbing phenomenon known as mitochondrial decay. Mitochondria are the engines of cells, converting the oxygen and fats and sugars we consume into energy. But just as all engines give off an exhaust, the cellular energy-conversion process gives off its own form of pollution, called free radicals - highly reactive atoms and molecules that clutter up the cell. Over time, this free-radical smog fouls up DNA and the cell's proper functions. Ironically, the very acts that sustain us - breathing and eating - eventually kill us. In 2002, Dr. Ames reported in the prestigious Proceedings of the National Academy of Sciences that he and colleague Tory Hagen may have found a way to reduce mitochondrial decay. They concluded that two compounds commonly found in health-food stores - lipoic acid and Acetyl L-Carnitine (sometimes used as a pick-me-up in Italy) - improved mitochondrial function as well as energy levels and cognition in aging rats. As Dr. Ames likes to say, "These old rats got up and did the Macarena." A friend persuaded him to launch a company - Juvenon - to sell the double-compound combination. He agreed to be its scientific director on the condition that all profits - the product sells for about $30 for a month's supply - go to clinical research. These days, Dr. Ames is also on a self-funded crusade (he has mortgaged his house) to convince scientists and governments that extremely common deficiencies in micronutrients are behind many of the degenerative diseases of aging. Cells lacking magnesium, for example, have a more rapid shortening of their telomeres, he says. The guinea pig Mr. Patton did have to wait: "It took five years and millions of dollars till I felt I had a pill in my hand that was safe enough to take," he says. But since the middle of 2007, he has ingested 50 milligrams a day of astragalus extract - twice as high a dose as he prescribes to anyone else, but only one-1,000th of the level his researchers determined would be toxic to human cells. He admits to feeling "a bit like a guinea pig." But he adds, "I feel absolutely great, more energy, more libido, my immune system is stronger. People tell me my skin looks better, healthier." He was having joint pain in his right knee, particularly on the tennis court, but now, he says, that pain is gone. Did astragalus extract solve it? "I can't say for sure," he admits. But he says lab tests at the University of California suggest the treatment has rejuvenated his immune system. Higher telomerase activity is associated with cancer cells, but Mr. Patton considers it only a theoretical risk that his pill could cause cancer. He points to research that suggests cancer is the result of several other mutations, not the mere activation of telomerase. It's also a comfort that the Chinese have consumed astragalus tea like chicken soup for centuries. He claims, however, that astragalus extracts at health-food stores do not contain the same active ingredient as his compound, based on his company's tests of four brands. TA Sciences' molecule, which it has dubbed TA65, was isolated from the plant's 2,000 other compounds. "We start with three tonnes of astragalus to make a very small amount," he says. Mr. Patton will not say if his pill is the same astragalus-based compound that Geron is now developing as a pharmaceutical to boost telomerase in immune-system cells. But he does maintain that it works just as well. In November, Geron's version, called TAT2, was the subject of an article in the peer-reviewed Journal of Immunology that found it boosted the immune system's ability to fight off HIV. Its lead author, Rita Effros, a professor of pathology and lab medicine at the University of California at Los Angeles, collaborated with Geron in 1996 showing that people with HIV have killer T-cells with shorter telomeres. Killer T-cells are like the front-line soldiers of the immune system; people tend to lose the fit ones as they age, in part because of a lifetime of battling viruses (making the elderly especially vulnerable to the flu and other infections). But people with HIV, who have T-cells at constant war with the AIDS virus, also have relatively few functioning T-cells. "Their immune systems look like they're aging prematurely," Dr. Effros says. Meanwhile, she adds, "We know that HIV 'controllers,' who never progress to AIDS, have killer T-cells with higher telomerase activity." In earlier experiments, Dr. Effros had shown that injecting the telomerase gene into T-cells taken from infected patients kept telomeres from shortening and better enabled the cells to fight HIV in a lab dish. But injecting genes into HIV patients is not a feasible way to treat the disease. As an alternative, she and her colleagues tested the astragalus compound: "We found we got just as much telomerase activity with TAT2 as we did with the gene therapy. "The difference," she says, "is that we had more control with TAT2. We could reduce the amount of activity - eliminate it completely." Dr. Effros feels the finding could have implications beyond HIV treatments. T-cells, for example, are also involved in bone loss. Human bones constantly undergo a process of destruction and re-creation, she said, "so that every 10 years you have a new skeleton." But with a chronic infection, the steady activation of T-cells and the immune system upsets the rebuilding of skeletal tissue and bones can thin. "If all this comes to pass, TAT2 could be used in HIV and bone loss and other diseases related to aging," Dr. Effros says. "That's the long-term, blue-sky vision." She cautions, however, against the idea that the compound could be used to make everyone live longer. "Anyone pushing to extend human lifespan is still on the fringe," she says. "I'm more interested in extending 'health span' - so one can just drop dead and not be sick for 10 or 20 years before that." Old, older - oldest? Still, some demographers do feel that history gives humans plenty of reason to expect longer life spans in the coming decades. Through most of evolution, people, like most species, died not long after the end of their reproductive period. Up to 1800, life expectancy in Europe was stuck at 40, and only in 1900 did it reach 50. But humans have made staggering gains in the decades since. In an article in Science in May, 2002, demographers James Vaupel of Duke University and Jim Oeppen of Cambridge University noted that life expectancy in developed countries has been growing by three months per year since 1840. "In 1840, the record for longest life expectancy was held by Swedish women who lived on average a little more than 45 years," they wrote. "Among nations today, the longest expectation of life - almost 85 years - is enjoyed by Japanese women." In industrialized countries, the average now hovers around 80 for women and slightly less for men. Most of the increase came thanks to improvements in sanitation and nutrition, and the advent of vaccines and antibiotics, along with more recent medical advances. With breakthroughs in genetics and stem cells on the horizon, some believe the lifespan trend shows no sign of slowing. But not everyone agrees. Jay Olshansky, a leading population expert at the University of Illinois in Chicago, is a strong supporter of scientific efforts to extend the healthy period of human life, but in a 2005 New England Journal of Medicine article, he argued that the rise of obesity could end the life-expectancy gains of the past two centuries. Dr. Martin-Matthews of Canada's Institute of Aging says the best evidence from scientists suggests that the human lifespan has a ceiling of about 120 years. But, she adds, everyone agrees that it's pointless to add 40 years to human life unless "we can reduce the incidence of degenerative disease." The challenge, she says, is to balance the rigours of credible research with the demands of a greying and impatient mass market. When three University of British Columbia scientists recently gave a public lecture on how to keep your brain fit as you age, 1,500 people showed up, she notes. "They had to keep finding a bigger room." While such public interest helps support their research, cautious scientists stress that no aging research has yet translated into a breakthrough. In 2002, in the wake of optimistic projections around life expectancy, 52 scientists involved in aging research published their Position Statement on Human Aging. They warned the public of the distinction between the "pseudo-scientific anti-aging industry and the genuine science of aging" and declared there is simply no intervention currently available to stop, slow or reverse the march of time. But that won't stop wishful mortals from hoping. Salvation or snake oil Even without a shred of hard proof, nearly 100 people have paid the $25,000 yearly fee for Mr. Patton's astragalus treatment regimen, which he has dubbed the Patton Protocol. It begins with taking 14 vials of blood from the customer and sending them to four different labs to undergo 90 different tests, including measurements for telomere length. (One of those labs is the immunology lab at UCLA.) The company also tests for cognitive function, bone density, skin elasticity and eyesight. Six months after the customers start taking the astragalus-derived pills, they return to have their biomarkers retested. "Customers have definitely improved. … No one's gotten worse," Mr. Patton says, adding: "The people who have completed their first year are coming back for a second year. … They're not hiring lawyers and suing me." He doesn't advertise, he says, because he has no studies on which to base claims. Most of his clients have come by word of mouth, and "almost all of them know about telomere biology," he says. "They're MDs and PhDs and they're not just buying any pig in a poke," he adds. "We're the only thing out there as a telomerase activator." Among Mr. Patton's clients is one of his competitors, Bill Andrews - the researcher who co-discovered the telomerase gene. Dr. Andrews is now CEO of the Nevada-based biotech research firm Sierra Sciences - where, Mr. Patton notes, the motto is, "We'll cure aging or die trying." Sierra has itself been chasing a telomerase activator. "You can take two telomere biologists," Mr. Patton says, "and one would say, 'This is too soon. It's a theoretical remedy. There are risks.' The other scientist would say, 'I'm taking it. My wife's taking it. It might save my life.'&#61486;" Still, does Mr. Patton feel any concern that it's premature - or unethical - to sell such a high-priced, unproven treatment? He knows how it sounds: "If you were to meet me at a cocktail party and ask me what I did and I told you I was selling something to immortalize your cells, you would think I was saying I'd found the Fountain of Youth for cells," he says. "You'd think I was a snake-oil salesman selling bullshit, and I wouldn't blame you." Then again, earlier generations might have accepted aging as inevitable - "aches, pains and deterioration, that's just fine," he says. But "now people are saying, 'No, that's not just fine.'&#61486;" So boomers who fear that they are running out of time to beat the aging clock are willing to take a chance on a product that might not have come through the traditional research pipelines. "There is an impatience in the market place and in the baby-boom generation - we want to keep running, discoing, having sex, using our brains," Mr. Patton says. "There's an urgency." Still, the fact that they "don't have 20 years of clinical trials that are double blind" eats at him. He is hoping to publish the first peer-reviewed paper on his pill's immunity-boosting abilities this year. But he knows he needs more clients in order to amass that data, a fact that - along with the soured economy - has convinced him to drop his annual treatment fee to just under $16,000. After all, he says, "finding a cure for aging 30 years down the road, when you're 80 now, is no help." Carolyn Abraham is the medical reporter for The Globe and Mail.

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