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Keeping Score
From his modern ninth-floor office on the Harvard Medical School Campus in Boston, Sinclair has a view that includes Fenway Park. “I can see the scores light up at night,” he says. I’m there on an oddly warm day in January, when a few trees are budding and the sky is crystal blue. On a shelf are a book by the Australian golfer Greg Norman called The Way of the Shark and a number of textbooks. Behind ­Sinclair’s desk are pictures of his wife and children.

Sinclair’s Harvard lab, now well funded, is working feverishly to clarify the health benefits of resveratrol and other compounds, and to discover exactly how sirtuins work on aging and the diseases of aging. In experiments involving thousands of mice, researchers are homing in on different sirtuin pathways and determining how they affect different diseases. Sinclair smiles and tells me they are getting great results, but he can’t say any more on the record. He does say he is working with Guarente on some experiments. “Lenny and I typically don’t work on things that aren’t important,” he says.

It has been two years since I last saw him, and in that time Sinclair has become more seasoned, more confident about fending off critics, and more comfortable with his stance as a scientist-zealot. “I am a science rebel,” he says. “That’s who I am. Everything we publish is criticized.”

In the conference room where I join his team to watch a presentation, the table is made of blond wood, and the black mesh chairs look expensive. Sinclair is dressed conservatively in a dark-red button-down shirt and gray slacks–not exactly the clothes of a rebel. A postdoc, Juan J. Carmona, gives a talk about what happens to the SIR system when a worm is exposed to the stressor of heat; Sinclair asks questions, pushing hard. Like most leading academic scientists with labs, he does little bench research himself, leaving the experiments to his students. His own success is highly dependent on their work. In the end, Sinclair looks pleased when Carmona describes how heat activated the sir2 pathway and increased life span in the worms.

Students in Sinclair’s lab say he sometimes seems driven, and he admits that he is: “I’m driven to get to goals as fast as possible. It frustrates people in my lab who have something they think is cool, but if it doesn’t move us forward, I don’t want to do it.” He says he views all the experiments being done at Sirtris, all his work, as part of a master plan. “I see this laid out in my mind, every step. But it’s happening faster than I imagined–it’s taking 10 years instead of 20 years.”

“When will it be ready for humans?” I ask.

“This will impact humans within a decade,” he says. “That’s why I don’t think there is anything more important than this quest. That’s why I take chances, and why the controversy is worth it: because I think we are right.”

He is also not averse to discussing the possibility that a Nobel Prize will someday be awarded to longevity researchers–something Lenny Guarente has also mentioned, though with the “I don’t really think much about it” attitude that is typical of senior scientists talking about the ultimate award. If such a prize is given, Sinclair says, Guarente and Cynthia Kenyon are likely to be two of the winners–out of a possible maximum of three.

“And the third person on the prize, who will that be?” I ask.

Sinclair smiles coyly and says nothing.

David Ewing Duncan is a freelance journalist. His last article for Technology Review was “Brain Boosters,” in the July/August issue.

To read a detailed explanation of the science behind resveratrol and sirtuins, go to technologyreview.com/sirtuins.

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Credit: Steve Brodner

Tagged: Biomedicine

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