THE AGE OLD PROBLEM; THE NEW SCIENCE OF HEALTH: PART THREE

As new anti-ageing products swamp the supermarket shelves and promises of eternal youth seem closer than ever, just what are the chances that we might live to be 200 and unwrinkled? Liz Hunt explores the latest scientific research in the death-defying race to prolong human life
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The Independent Culture
For most of human history, man's only hope of living forever has been to die first. Eternal life, with death reduced to a transient state en route to the hereafter, has been the most popular means of avoiding eternal oblivion.

But now death itself is under siege as never before, as chemical and genetic manipulation of the ageing process and its terminal consequences, become real possibilities. Evidence against the "wear and tear" theory of ageing is growing, suggesting that it is a process that can be tinkered with - mankind may one day have no need of a hereafter because life on earth will just go on and on.

Fruit flies and worms are the major beneficiaries of the Methuselah-mania that is currently sweeping through laboratories worldwide, but it is more scientific fact than fiction which has respected scientists and learned scientific journals discussing the prospects of human life measured in centuries rather than decades.

Dr Michael Rose, a British-born geneticist now based at the University of California at Irvine, and the man credited with almost single-handedly bringing "the evolutionary theory of ageing from an abstract notion to one of the more exciting topics in science," has, by selective breeding techniques, managed to double the life span of his laboratory fruit flies.

This, he says, corresponds to a human life span of around 200 years. Dr Rose is now planning to extend his work to mice, a more useful genetic model for man than the 500 generations of drosophilae he has bred over the last 20 years.

Meanwhile, scientists at McGill University in Montreal recently published research in the journal Science, showing how they had genetically altered worms to live almost seven times longer than normal. And Cynthia Kenyon, professor of biology at the University of California in San Francisco, has succeeded in breeding nematodes, microscopic worms found in the soil, which buck their expected life-span trend. At eight weeks old - positively senile in nematode terms - they are as vigorous as they were at two weeks old.

By studying these longer-living flies and worms, and extending the work to other species, scientists hope to determine how the Meth-uselahs differ from their "normal", shorter-living brothers and sisters; what hormones, enzymes, or other biologically active proteins they make more or less of, and at what stage in their life cycle. It may then be possible to devise therapies which will make humans live longer, according to Dr Rose.

In a recent interview published in The New Yorker magazine, he fast-forwards to a future in which popping anti-ageing pills - clinically proven to be effective in total contrast to the extremely dubious panaceas like DHEA and melatonin which are the current fashion - is the accepted norm. "You'll have a big, elaborate industry ... which will involve companies that turn out many products for a considerable amount of money, so that people are going to have to spend a very significant fraction of their income every year on products that will keep them young and robust," Dr Rose confidently predicts.

Certainly that is what the Geron Corporation in San Francisco is hoping for. It is the world's first biotechnology company devoted to developing drugs to treat ageing, and is at the forefront of what is known as telomere theory. It is an area of research which has sprung up only in the last five years, and focuses on the caps of DNA - telomeres - that sit on the end of human chromosomes. The exact function of a telomere is not known but it has been observed that each time a cell divides, it gets a little bit shorter. The older a person is, the shorter these DNA caps on the chromosomes.

Telomere experts such as Carol Greider at Cold Spring Harbour Laboratory on Long Island, and Calvin Harley, chief scientific adviser at Geron Corporation propose that telomeres regulate the ageing of cells. They argue that telomeres have a critical length below which a cell cannot divide further, and this is when the ageing process kicks in. If the shortening of telomeres could be halted, or a means found of lengthening them, in theory at least, the ageing of the cell could be stopped in its tracks. This theory also offers a route to another of medical science's holy grails, a cure for cancer, predominantly a disease of ageing.

In the mid-Eighties, scientists discovered a protein known as telomerase, an enzyme which can replace all the bits of telomere lost during cell division, and stop it shortening. Cancer cells, rogue cells which divide repeatedly short-circuiting the normal growth controls imposed on a cell, are rich in telomerase. Healthy cells are not; they possess the ability to make the enzyme but the genetic switch regulating its production has not been flipped on. Developing a therapeutic approach which targets the switch in cancer cells could actually limit tumour growth and spread. Alternately, manipulation of the switch during life could also prevent cell senescence.

Telomere theory has lead to a plethora of articles in serious science journals in the past year, some of which have filtered down through less specialist media because of its implications for an age-old question: how can we live for ever? Tom Kirkwood, a gerontologist at Man-chester University, attempted to answer it in a recent issue of the British Medical Journal. Or rather he didn't, pointing out that living for ever was a myth and "sooner or later an accident would catch up with us, even if we did not age."

He argued that the best recipe for longevity was to choose one's parents, in the same way that Dr Rose chose his longest-living fruit flies to breed from. In 1993, scientists published the results of their investigation into a sample of twins living in Denmark in the 19th century, and concluded from their research that genes are responsible for a fifth of the variance of life span.

But we cannot choose our ancestors; we must make the best of whatever genetic legacy we possess, and it may be some time yet before Miller Quarles, an 81-year-old millionaire from Texas, has to part with the $100m he is offering as a prize to the person who discovers a "cure for the disease of ageing". In the interim, men and women who want to live longer and look younger, are turning to more accessible solutions.

Business in "anti-ageing" hormones, youth-enhancing food supplements, diet pills, virility enhancers, and plastic surgery, is booming. The cult of youth and beauty which pervades Western society is partially responsible, and in a diminishing jobs market a youthful appearance and outlook is considered an asset. But the trend is fuelled by the influence and purchasing power of that over- indulged demographic group, the baby boomers.

Millions of baby boomers will turn 50 this decade, and they are reaching middle-age, fitter, more active, more youthful-looking - and more determined to preserve it all - than any preceding generation. They grew up benefiting from advances in public health and medical science, free from the scourge of diseases such as tuberculosis and smallpox, and with better housing, hygiene, and food. High-tech operations, such as coronary by-passes, are available to them, as are potent drugs which relieve symptoms, and control or eradicate illness.

Although life expectancy has increased these extra years mean little if they are spent as wrinkled, fragile beings, who are overweight, tired all the time, increasingly forgetful, and burdened with a flagging libido.

A careful diet, regular exercise, and the odd vitamin pill to rev the engine, are the cheapest and most reliable routes to a healthier old-age. But they are not enough - and require too much self-discipline - to achieve the Dorian Gray-like miracles now being sought. The other best known routes to longevity, a significantly reduced calorific intake throughout life, or castration, are not viable alternatives. It is, predictably, the American baby boomers who, with the aid of various doctors anxious to jump on the anti-ageing bandwagon, are turning in their millions to growth hormone injections, testosterone and oestrogen patches, and other hormone-like compounds such as melatonin and DHEA. In the UK, our pursuit of eternal youth is less aggressive at present and there are tighter controls on what can and can't be sold or prescribed to provide it, but there is a burgeoning interest being taken in such matters.

DHEA, sold as a food supplement in the United States but now available only on prescription in the UK because of safety concerns, is the current favourite of those eager to drink at the fountain of youth. In breathless prose, books such as The Super-Hormone Promise, and The DHEA Breakthrough, first published in the United States and now being translated for the UK consumer, are promoting the virtues of this miracle answer to preventing cancer and heart disease, restoring sexual vigour, improving cognitive function, and halting middle-age spread.

DHEA is dehydroepiandrosterone, which is produced in the body by the adrenal glands, and to a lesser extent in the testes and ovaries throughout life. As we age, our bodies produce dwindling amounts of DHEA; high levels are linked with good health and a primed immune system while low levels are linked with infirmity and death. However, there is not much else known about it, or much in the way of supporting evidence for the extravagant claims now being made for it.

It has been tagged "the mother hormone" because it is the precursor for all sex hormones, including oestrogen and testosterone, and for the "stress" hormone cortisone. DHEA is a biologically active substance, but research into its therapeutic dose range, its long-term effects on hormone-sensitive tissues in the breast and prostate gland, or its impact on the brain is scarce, hence the concern of British scientists. Professor Geo-rge Fink, of the Medical Research Council's Brain Meta-bolism Unit in Edinburgh, said: "It does have some effects on the brain. Until we know more, I don't think it would be wise to use it." Recent studies on rats at the Northwestern University in Illinois support this cautious stance: 14 out of 16 rats fed DHEA developed liver cancer.

Melatonin, another hormone, is no less troublesome - and untested. It is also available in the United States as a food-supplement and was available from some health-food shops in the UK until the Department of Health banned its supply in 1995. The DOH regards melatonin as a medicinal product which should be licensed accordingly. The Melatonin Miracle, and other upbeat books have advocated its use for treatment of jet-lag and other sleep disorders, to boost immunity and as a cancer preventive. But in an article in the journal Cell, published last year, Steven Reppert and David Weaver from Harvard University, pointed out that the original experiments which triggered the melatonin craze were conducted in mice which, because of a genetic defect, were unable to produce melatonin themselves. When melatonin was given to mice able to produce the hormone, as indeed humans are, they developed cancers of the reproductive tract.

Human growth hormone, used for decades to successfully treat short stature in children, is also the subject of a new sales pitch, following claims that it will preserve lean body mass, improve skin and hair quality, boost immunity, improve heart and kidney function and all-round well-being, in middle-aged men. Doctors at the various "youth clinics" and "life extension centres" that are springing up in the United States, are already prescribing it for this group, despite few long-term studies of its effects in adults, and known risks such as diabetes, fluid retention and enlarging of bones and internal organs. It is unlikely that many doctors in the UK could be persuaded to prescribe it for this purpose - at present.

More is known about testosterone, the fourth "youth" drug in the currently available armamentarium. It has been used for years to treat hypogonadism, a rare condition in which young men have abnormally low levels of testosterone. It has also been used illegally by athletes to boost their strength and endurance while training. Testosterone- reducing therapy, mean-while, is administered to some convicted sex offenders in order to reduce their libido.

However, it is only with the recognition of the andropause, or viropause, as the male equivalent of the menopause - and the majority of doctors are still sceptical about the existence of this condition - that the clinical use of testosterone as a possible anti-ageing drug has been raised. It is claimed to revive libido and lower total cholesterol, as well as maintaining muscle mass. The advent of testosterone patches means that male HRT is as readily available as oestrogen HRT for women, and some British doctors are prepared to prescribe it for this purpose. But just as oestrogen replacement therapy comes with a health warning, testosterone is not without its risks either. It reduces levels of the "good" type of cholesterol, known as high-density lipids; it blocks sperm production and, in some cases, can trigger or stimulate the development of prostate cancer.

Until the discoveries made in fruit flies and worms can be applied to humans, or telomere theory is translated into therapeutic interventions, it seems that a high price must be exacted for trying to slow, or reverse the ageing process. Although science can prolong life to a degree that would have been unimaginable a century ago, in reality we appear to have more in common with the Struldbruggs or Immortals of Jona-than Swift's imagination. They lived forever but with all the infirmities and sorrows of old age, and none of the vigour and joys of youth that is our understanding of immortality.

In an article in the British Medical Journal, Professor James McCormick in the Department of Community Health and General Practice, Trinity College, Dublin, summed it up thus: "As somebody who looks after several people who are living to die the slow death of senescence, there seems to me a strong case for relatively early and speedy death. In a world where all women are taking hormone replacement therapy and all men are taking statins [cholesterol-lowering drugs], the possibility of a peaceful myocardial infarction [heart attack] will diminish, and many more of us can look forward to a life 'sans teeth, sans eyes, sans taste, sans everything'."

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