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Never Say Die
NEWSWEEK
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.
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