Never Say Die

None of this proves that SIRT1 extends human life. But both Kenyon and Sinclair have helped set up businesses to pursue clinical applications of their work. Any drugs that result will not be approved for longevity, since the FDA approves drugs only to treat illnesses. Instead, both Sinclair's Sirtris Pharmaceuticals and Kenyon's Elixir Pharmaceuticals are pursuing pills for diabetes, one of the leading diseases of aging. Sirtris's formulation of resveratrol has been shown in early trials to lower blood sugar and insulin in patients with type 2 diabetes, and the company is entering trials with synthetic sirtuin activators that are up to 1,000 times more potent than resveratrol. Though 60 to 90 percent of drugs at these stages of testing ultimately fizzle out, GlaxoSmithKline purchased Sirtris over the summer for $720 million. "Half a dozen major drug companies are working on sirtuins," says Dr. Christoph Westphal, CEO of Sirtris. "Because they affect many diseases of aging, the potential market is huge."

Other future blockbusters could be drugs that repair telomeres, the DNA caps on the ends of chromosomes. Every time a cell divides, the telomeres become shorter. When they shrink too much, cells stop replicating and start to function poorly. The result is wrinkling and general deterioration—well-known problems of aging. But scientists hope to forestall the effects by boosting telomerase, an enzyme that rebuilds telomeres. "There are rare families with very low telomerase," says molecular biologist Elizabeth Blackburn of UC San Francisco. "They never make it to old age. They die first of infections, cancers or lung fibrosis."

That doesn't prove that boosting telomerase extends years of health. But it's a reasonable hypothesis. Last month the first evidence in mammals surfaced in a study from Spain. Mice that were bred to have enhanced levels of telomerase lived 40 percent longer—and had better glucose sensitivity and motor function, stronger skin and less inflammation. The relevance to humans is open to debate. But UCLA immunologist Rita Effros also published a study last month on immune cells that were drawn from people with HIV. The cells were treated in the lab with a telomerase activator from Geron Corp. "Sure enough, they killed viruses better, divided longer and acted more youthful," Effros says. It's not just people with HIV who stand to benefit. "Many diseases of aging involve a weakened immune system," she says. But because too much telomerase could theoretically boost cancer risks, "it will be a long and difficult job to make sure a telomerase drug is safe," says Blackburn.

Some folks aren't waiting. Telomere biologist Bill Andrews of Sierra Sciences is taking a telomerase-boosting supplement called TA-65. "I believe it's safer than driving my car to work," he says. Since he started taking it a year and a half ago, Andrews says he has moved from the back of the pack to the front in 100-mile runs known as ultramarathons. But don't expect to find TA-65 at your local Vitamin Shoppe. It is available only from TA Sciences—for $25,000 a year. And customers have to undergo a battery of tests every six months to gauge the results, none of which have been published yet.

It might be smarter to save the $25,000 and modify your lifestyle. Last month Blackburn published a study showing that 30 men on Dr. Dean Ornish's program (an ultralow-fat diet, exercise and stress reduction) increased their telomerase levels by 30 percent. "According to the World Health Organization, 80 percent of heart disease and 40 percent of cancers could be prevented with a healthy diet and lifestyle," says Fontana. For those of us in the wrong end of the gene pool, healthy habits may be the best life preserver around.

With Karen Springen

© 2008