July 17, 2007 — -- Controlling aging with drugs is a remarkable idea, and some might say an outlandish one. But two Massachusetts scientists say they're enticingly close to making the idea a reality.
The brains behind the idea are Harvard Medical School scientist David Sinclair, 38, and millionaire investor Christoph Westphal, the 39-year-old CEO of Sirtris Pharmaceuticals.
They say they hope the research they're doing in Cambridge, Mass., the biotech hub of the universe, will revolutionize medicine.
"If we are right, these drugs will be enormously successful drugs and treat very important diseases," said Westphal.
Inside a nondescript building, the co-founders share a tiny office and a goofy sense of humor. But the company's goal is quite serious. They hope to develop drugs that will treat not just some but potentially all the diseases that come with old age -- diabetes, Alzheimer's and Parkinson's, for example.
"I used to think it was probably 100 years in the future that we'd see these anti-aging drugs come around," said Sinclair, "but now I'm optimistic that we'll see these within the next, possibly within the next few years."
Sirtris was founded based on the science of David Sinclair. He was something of whiz-kid when he was recruited by Harvard Medical School and given his own lab devoted to research on aging. He still spends most of his time there, where he and his team do what he calls cutting-edge science.
Sinclair said from the moment he realized he was mortal, he was on a quest to do something about it. So after finishing his Ph.D. in his native Australia, he sold his car to buy a plane ticket to Massachusetts.
There, he began working in an MIT lab that was doing groundbreaking research on the genetics of aging.
"The simple fact that there are genes that control aging is really one of the most important discoveries in the last decade or more," Sinclair said. "But the details of what these genes actually do and how they do it, we're really just beginning to tap into that and the more we study, the more exciting it becomes."
Exciting, because he said the genes are activated by a red wine ingredient called resveratrol. Mice that received it in their study lived 30 percent longer than the mice that did not.
That finding made big headlines, and grabbed the attention of Christoph Westphal, who is now Sinclair's business partner.
Westphal is an M.D.-Ph.D., which he finished in almost-record time at Harvard. But he's made his name and his fortune as a venture capitalist, investing in edgy biotech companies. Westphal explained that his first meeting with Sinclair wasn't all red wine and roses.
"There was a little bit of a chess match at the beginning, where we were all trying to figure each other out," explained Westphal.
"He basically said, tell me all, or I'm going to walk out of here," said Sinclair. "And I realized pretty quickly that he was a guy that I wanted to tell things to because I thought he was somebody very special."
Special indeed. Originally from Germany, Westphal paid his way through medical school by performing as a concert cellist. He's also fluent in four languages.
So when the two paired up, it was something of a dream team. But they still needed backing.
"It's tens of millions of dollars to set up a company like Sirtris, and ultimately hundreds of millions of dollars to develop a drug," said Westphal.
Westphal raises those millions by selling investors on the promise of those mice.
"If we're right, this is a game-changer," he said. "There's very few things I've ever seen in my life, and I've looked at a lot of these technologies, that if the technology is right, and the drugs actually deliver on the promise of the science, it's a game-changer."
So, how exactly will red wine do that? The approach starts with a very simple idea: dieting. Serious dieting.
"There is a very simple way to slow down aging in animals. It's called caloric restriction. And this is a diet that was discovered 70 or more years ago by scientists in the United States. And what they found was that if you restrict the amount of calories a rat or a mouse gets throughout its lifespan by about 30 percent, they live dramatically longer -- about 30 to 50 percent longer."
"So these same rats, these control rats that are on a normal diet have cancer and are dying from all sorts of horrible diseases, while the rats on the calorie-restricted diet are running around the cage. They don't have cancer."
Scientists have spent decades trying to figure out why. Sinclair believes he's discovered the answer in a gene that gets switched on when you stop eating.
The gene starts producing an enzyme that puts your cells in defense mode, making the body more able to fight off disease.
"So instead of having to calorie restrict your whole life span, which nobody really wants to do, your life may not be longer but it will certainly feel that way," said Sinclair. "What we hope to do is have a pill that will be able to be taken safely, hopefully for many years, and to give you the same benefit of this diet that we see happen in rats, this remarkable effect against aging and diseases of aging."
The pill would mimic the benefits of the restrictive diet, without having to limit your actual diet.
That brings us back to that bottle of red wine and resveratrol, wine's magic ingredient.
"Think of a Pac-Man controlling things in the cell, and resveratrol binds to the Pac-Man and makes it more active," Sinclair explained. "And tells the cell to be more efficient, ramp up metabolic rate, and overall health of the cell and [is] resistant to diseases of aging."
Sinclair's research shows that's what happens in mice, as well as in yeast. But will it work the same way in humans? That remains to be seen.
"This is very pure resveratrol, which is pure enough to go into human studies," said Westphal, whose team is currently trying to discover how much resveratrol humans need to receive benefits.
The human trials are currently taking place, and they say they expect results around the end of the year. "I think the biology is very strong, and so I'm willing to bet my career that it is very likely to be right," said Sinclair.
Matt Kaeberlein, who's a former colleague of Sinclair's and a specialist on aging, said Sirtris is taking a risky bet.
"There have been many findings that were at first thought to be extremely important and extremely exciting but didn't live up to the hype," he said. "There are many other cellular targets of resveratrol that could be accounting for some of these beneficial effects, and that hasn't really been explored."
In other words, what's in that glass of wine might be helpful, but perhaps not for the reasons Sirtris thinks.
"Well, I don't believe we need to fully understand what these genes do to make a drug that will work," said Sinclair. "Many of the drugs that we take today, we don't know what really, the downstream effects are. It's very complex. The body is complex, I'm not denying that."
"The specifics, the very fine specifics about the mechanism which might be part of the sources of academic conflict," Westphal admitted. "To the company, it's not that important, but all we care about is, are we right? And will it work in man?"
While they wait to find out, should the rest of us start pouring the pinot noir?
"Probably, if you wanted the health-giving effects of resveratrol from red wine, you'd have to have a couple of hundred glasses of wine," said Westphal. "Per day."
That's why Sirtris is hoping to pack the power of resveratrol into a tiny pill. But in the meantime, you can buy a lower dose of resveratrol at health food stores. What is unclear is whether the over-the-counter versions work, or whether they're safe.
Kaeberlein points out that even if those resveratrol supplements work in humans, there's still not enough concrete evidence to start taking it regularly.
"There is no safety data on resveratrol, particularly long-term safety data," he said. "I would be particularly wary if I was taking a prescription drug. One of the targets resveratrol is known to act on are enzymes that influence the way certain drugs are metabolized. So there's certainly a possibility of drug interactions."
If this endeavor fails, Westphal admits he'll be disappointed. But if it succeeds, "It's going to be great. It can change the world."
So, despite the doubt -- and the risk -- behind their venture, these two are willing to drink to the idea that they've uncorked the secret to longer, healthier lives.