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Thursday, Aug. 30, 2001

NATURAL SELECTIONS

We can't stay young forever, but why not age gracefully?


Following recent reports of a mammal able to regenerate after injury, science continues to imitate fiction, with a discovery in Boston that recalls the search for the philosopher's stone. The stone, the subject of the first Harry Potter book, was long sought after by medieval alchemists, who believed it would provide the elixir of life, but scientists from Boston have succeeded where the alchemists failed. The secret to aging has been found, not in a stone, but in chromosome 4.

Howard Hughes Medical Institute researcher Louis Kunkel led a team that scanned the genome of exceptionally long-lived siblings and pinpointed the location of genes that appear to be associated with living for 100 years and more.

The secret has been "found" before, closer to home. Okinawans live longer, on average, than people in other parts of Japan, who themselves can expect to live longer than people in the rest of the world. Centenarians usually remain active and in good health. (The BBC once reported about a 105-year-old Okinawan woman who clubbed a poisonous snake to death with a fly swatter.) How are these people protected from cardiovascular disease, cancer, Alzheimer's and strokes? If it's not the philosopher's stone, what is it?

Scientists say aging is a very complicated process. This sounds suspiciously like shorthand for "we don't understand it," but it underscores the fact that there are likely to be many factors that contribute to the decay and disease associated with getting old. Environmental factors such as diet, climate and stress levels -- thought to be key to the longevity of Okinawans -- are likely to be important influences.

What about the genetics of aging? Most researchers in the field thought that as many as a thousand genes would contribute to such a complex trait as human aging, but the new research, published this week in the Proceedings of the National Academy of Sciences, suggests otherwise.

In lower organisms such as fruit flies, nematodes and yeast, researchers have found that you need only to alter a few genes to increase life span. Based on this, Kunkel, who is also chief of genetics at Children's Hospital Boston, started a search for longevity genes in humans.

To qualify for inclusion in the study, subjects had to be at least 98 years old and have a living brother of at least 91 or a living sister of at least 95. The search for the long-lived siblings began in 1997. Eventually, the researchers had found and verified the ages of enough siblings to go ahead with a genome-wide comparative analysis of their genes.

Using blood samples from 137 so-called sibship pairs, for a total of 308 people of predominately European descent, researchers scanned their genomes for similarities. The search located a small region of chromosome 4 that most of the venerable sibs had in common. That region is likely to contain a gene or genes associated with extreme longevity.

Kunkel warned that this is only the beginning of a long research plan to identify the longevity genes. "This is an extremely complicated process because there are perhaps as many as 500 genes in this region," Kunkel said, "and one of them has a single sequence variation that confers this phenotype [the trait in question, i.e. longevity].

"This variation is not a mutation as in genetic disease. Rather it is a very subtle genetic difference that produces a protein that may either work slightly better or be less active than in the normal population."

And if the products of the key genes can be synthesized, will science have reproduced the fabled elixir of life?

"We're not trying to find the fountain of youth," emphasized Thomas Perls, a geriatrician at Beth Israel Deaconess Medical Center and a coauthor of the study. "If anything, we're trying to find the fountain of aging well."

Even the "fountain of aging well" would be clearly in high demand. Despite their rarity, centenarians are the fastest-growing segment of the U.S. population, according to Perls. The research will help identify why centenarians age so slowly, delaying age-related diseases such as Alzheimer's and cancer or entirely avoiding them. Drugs that could mimic what centenarians have genetically? You can almost hear the ka-ching of cash registers everywhere.

People are already willing to pay for their heads to be cryogenically frozen after their death and for their favorite dogs to be cloned: Imagine what they'd pay for what would inevitably be seen as an antiaging drug? Surely it would take its place alongside the other recently patented genetic discoveries, but according to Annibale Puca, lead author of the paper, "If we are able, in a few years, to discover a drug for 'aging well,' then everybody can use it."

E-mail Rowan Hooper at: rowan@japantimes.co.jp


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