Even if Sirtris’s compounds don’t pan out as safe, effective drugs, the enzymes behind them have great medical potential, says Matt Kaeberlein, an assistant professor in the pathology department at the University of Washington, who is another former student of Guarente’s and a consistent critic of some of Sinclair’s work. These enzymes have been highly conserved through evolution, appearing in worms, flies, mice, and primates, and they play a central role in the biochemistry of the cell. Guarente says, “If the whole world gave up on sirtuins, I would still start another company for the next generation of sirtuin drugs based on what I know.”
But some scientists doubt that sirtuins hold the key to life extension; for one thing, sirtuin activation hasn’t been shown to extend life in healthy animals. A number of other molecular mechanisms are also under close scrutiny for their effects on aging. Kenyon, director of the Hillblom Center for the Biology of Aging at UCSF, points to a different drug, called rapamycin; as Stipp explains, one way it appears to lengthen life is by slowing the production of the proteins needed for cell division. As more proteins are produced, so are more defective proteins, which can accumulate in cells and contribute to the symptoms we see as aging.
Though rapamycin has not gotten nearly the attention or money that sirtuins have, some put far more faith in its age-slowing effects. “I’ve been in this area for about 35 years, and I honestly have never thought that in my lifetime there would be something like a pill that you could take that would have this impact on aging,” Arlan Richardson, director of the Barshop Institute for Longevity and Aging Studies at the University of Texas Health Science Center at San Antonio, says of the drug. Aging “may not be as intractable a problem as I thought,” he says. Rapamycin even worked on adult mice equivalent in age to 60-year-old people.
So why isn’t rapamycin more talked about? “The scientists involved with the rapamycin studies have been much less inclined to make bold claims,” Kaeberlein says. “That may be in part due to the fact that the mouse rapamycin studies were done as part of [a government] testing program, so there’s no commercial interest involved in selling a story.” But if sirtuins and rapamycin don’t work, researchers say, there are plenty of other possibilities to explore, from insulin signaling to mitochondrial function.
Stipp and others are confident that a “youth pill” is on the horizon–whether it comes from Sirtris or not. But some researchers are far less optimistic. Thomas Perls, for one, thinks it’s reckless to suggest that science is anywhere close to such a drug. “I think people just don’t get how incredibly complex aging is,” says Perls, an associate professor of medicine at Boston University’s School of Medicine, who for the last 16 years has run a study on centenarians. “Delivering the message that antiaging works, and that we’re now in prime time in producing substances that work, is incredibly irresponsible.”
Karen Weintraub is a freelance writer based in Cambridge, MA. She is the former Deputy Health/Science Editor at the Boston Globe.