The thinking was this: Calorie-restricted animals survived longer, in many cases 30 percent longer, because the process activated a family of genes that produce proteins called sirtuins, substances that directly altered the metabolic activity of cells in ways thought to stave off diseases of aging.
When a team of scientists from Harvard reported in 2003 that a compound in the skin of red grapes called resveratrol seemed to activate sirtuins—and caused obese and diabetic mice fed a high-fat diet to live longer—sales of red wine and resveratrol dietary supplements shot through the roof.
In recent years, however, snags in the science have suggested the rush for resveratrol supplements may have been premature. A fierce and public debate has since emerged with camps of researchers publishing contradictory studies.
Scientists have had difficulty reproducing some of the original resveratrol findings. And studies in yeast, flies, and worms have questioned whether resveratrol really activates sirtuins and whether sirtuins are as instrumental to aging as first thought.
Meanwhile, in the human research realm, the drug maker GlaxoSmithKline terminated a clinical trial of a concentrated form of resveratrol that doctors had been testing on cancer patients because of unexpected side effects on people's kidneys. In the spring of 2012, it even came to light that a University of Connecticut researcher had allegedly falsified numerous studies suggesting that resveratrol has positive health effects.
But none of this means that nothing will ever come of sirtuins. Despite the controversy, a steady stream of studies continue to materialize and show that sirtuins play an important role in aging. A new study in the May issue of Cell Metabolism, for example, argues that there's a clear connection between resveratrol and sirtuins and suggests that sirtuins are key to slowing down the aging process.
Meanwhile, Sirtris Pharmaceuticals, the company that had been testing resveratrol for GlaxoSmithKline, has a number of newer, more potent and targeted sirtuin compounds in its pipeline that resemble resveratrol but are structurally distinct.
There's nothing particularly unusual about having a compound that works in the lab prove problematic in humans: In drug development, there are often false starts and dead ends. "People forget that we're not mice," Sierra says. "And what works in mice doesn't necessarily translate to humans as cleanly as we'd like."
Most researchers studying longevity believe that drugs to combat multiple age-related diseases will emerge eventually, just not for decades. In the meantime, Sierra does not advocate popping resveratrol or any of the other anti-aging pills already on the market. "We're still in an early stage of research," he says. "I don't have a tail. I don't have whiskers, and I won't take anything until we have good studies in humans showing a drug is safe and effective."
Until then, his anti-aging medication of choice is exercise.