Forever Young

The new scientific search for immortality

Ronald Bailey from the August/September 2002 issue

(Page 4 of 6)

The true fountain of youth will involve stopping those pesky free radicals that are wrecking your DNA and cooking your tissues to death. The most popular anti-aging regimen, practiced by millions of Americans, is to pop anti-oxidant vitamin and mineral pills. There is no firm scientific evidence that gobbling down such supplements actually increases life spans. Simon Melov of the Buck Institute for Aging Research notes that the effects of anti-oxidant pills are fairly weak, since most of the nutrients don't get inside the cells where the free radical damage is occurring. Jay Olshansky dismisses megadose vitamin supplements as "a way to make expensive urine."

On the other hand, Olshansky admits that some people can benefit from vitamin supplements. Epidemiological studies show that vitamin E supplements might help 12 percent of the population. The problem is, each individual has no way of knowing now whether he or she is part of that 12 percent. Nevertheless, many of us cover our bets by taking supplements anyway.

A recent study conducted by Bruce Ames' team at Berkeley found that lethargic old rats are perked up by l-carnitine and alpha lipoic acid. Their mitochondrial function improves, they become more active, and their memories get better. A company called Juvenon, founded by Ames and others, is testing the supplements in people with the goal of finding an effective human dose.

Meanwhile, Thomas Perls of Harvard is hunting for longevity genes. Perls noticed a decade ago that people who live to be 100 are often in remarkably good shape. Today, he runs the New England Centenarian Project, whose participants must be 100 years old and have siblings who lived to be over 90. By looking at DNA taken from some 600 participants so far, Perls has found that a region on chromosome four appears to help its carriers become healthy geezers.

Perls and his colleagues have formed a company called Centagenetix to narrow the search for the longevity gene. Once it's identified, Centagenetix will try to produce a Methuselah pill that mimics the activity of the proteins made by the longevity gene.

The M.I.T. biologist Leonard Guarente recently showed that nematode worms with more than one copy of a gene called SIR2 live 50 percent longer than normal worms. This may explain why calorie restriction increases life span, because SIR2 slows down gene activity when a cell is being starved. Guarente and Cynthia Kenyon have already identified genes and enzymatic pathways that increase the life spans of invertebrate species. They believe that these same mechanisms will be found in people, giving them targets at which to aim anti-aging drugs. Guarente and Kenyon have created a company called Elixir, which will try to develop such pharmaceuticals.

Eurkarion, a privately held biotech start-up in Massachusetts, is working with the Buck Institute's Melov to test its novel small-molecule anti-oxidant compounds. Melov has genetically engineered mice that don't produce superoxide dismutase, the oxygen-scavenging enzyme that protects mitochondria from free radicals.

Such mice typically die within a week after birth. They suffer from enlarged hearts, damaged livers, and a spongiform brain ailment that looks very much like mad cow disease. But when these mice are injected with compounds that mimic the effects of superoxide dismutase and catalase (a compound that transforms hydrogen peroxide into water), they live four times longer. Eukarion is currently testing one of its compounds as a topical application to heal skin damaged by radiation treatments. It plans to test further compounds as treatments for degenerative neurological diseases in human beings.

As for the gunk built up in our cells, researchers are testing some compounds that break apart AGEs, enabling cells to get rid of them. In preliminary testing, a compound called Pimagedine has improved cardiac function in rats, dogs, and primates. It is also being tested for efficacy in treating kidney failure associated with diabetes. Another anti-AGEing compound, ATL-711, has shown some promise as a treatment to reverse age-related and diabetes-related cardiovascular diseases and restore function to the cardiovascular system.

Runaway Hormones

What about lengthening telomeres? Remember, our immortal germ cells activate the gene that produces the enzyme telomerase, which restores the ends of their telomeres whenever they divide. Cancer cells also stimulate production of the enzyme. The Geron Corporation is conducting research into how to use telomerase to fight cancer. The idea is that if you can turn off telomerase in the cancer cells they will stop dividing and commit cellular suicide, called apoptosis.

Some researchers have suggested that it might be possible to make normal cells immortal by getting them to produce telomerase, which could prevent the shortening of their protective telomeres. It seems logical that if telomere shortening causes cells to become senescent, lengthening them should rejuvenate them and the tissues in which they reside. Still, according to Barbara Hansen, there is little evidence that telomere shortening causes senescence on the organism level.

Hormone replacement therapy is second only to vitamin supplements in popularity among those seeking the fountain of youth. The aim here is to restore the hormones that decline with age to their youthful levels. The most popular hormones involved are DHEA, human growth hormone, melatonin, testosterone, and estrogen.

The notion that hormones could restore youth has a long and disreputable history. In the late 19th century the noted French physiologist Charles Edouard Brown-Sequard injected himself and his patients with extracts from the testicles of young dogs and guinea pigs, then declared that the treatments had restored his physical vigor and mental acuity. In the early 20th century the American John Brinkley claimed to restore men's vitality by transplanting goat testicles into them. He performed over 16,000 transplants before he died, though his medical license was revoked after some of his customers claimed a new compulsion "to chew sprouts."

More recently, hormone replacement therapies took off after the endocrinologist Daniel Rudman reported in 1990 that a dozen older men he had injected with growth hormone three times a week had more muscle mass, less fat, tauter skin, and lower cholesterol levels. Subsequent studies have shown that these quality-of-life benefits are real but slight. In fact, regular exercise is more effective in obtaining most of the gains achieved from injecting growth hormone.

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