June 23, 2010

Technology Review: The Argument over Aging

MIT's Technology Review wonders if a drug can extend good health and postpone the effects of aging. Early results are not promising:
In 2003, Sinclair made headlines around the world when he announced that the red-wine component resveratrol, which had previously been linked to a reduction in heart disease, extended life span in yeast. He argued that the compound activated one of the sirtuins and proposed that it mimicked the effects of caloric restriction. Sinclair and Westphal launched Sirtris in 2004 with the aim of developing molecules that could stimulate the enzyme much more potently. The company is developing treatments not for aging itself--which the U.S. Food and Drug Administration doesn't consider an illness--but for diseases of aging, such as diabetes, Alzheimer's, and cancer.

As Stipp recounts, hopes for antiaging drugs captured media attention and investors' imaginations. But a different conversation has played out in the academic community. Some scientists doubted whether resveratrol truly targeted the sirtuins. Researchers at drug maker Pfizer also published a study in January questioning whether one of Sirtris's newer compounds targets the enzyme. The study failed to confirm the health benefits seen in earlier trials. To make matters worse, safety concerns have arisen over one of Sirtris's resveratrol compounds. In May, Glaxo announced that it would not expand a clinical trial for multiple-myeloma patients until it better understood why some participants developed a dangerous kidney ailment.

The field of antiaging research is littered with failures, and the controversy over Sirtris's compounds highlights just how difficult it has been to transform exciting scientific discoveries about the aging process into useful drugs. As Stipp illustrates, many candidates with promising antiaging benefits later failed to work in mammals or showed conflicting results.

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