A professor of genetics at Harvard Medical School and co-director of the university's Paul F. Glenn Laboratories for the Molecular Biology of Aging, he has founded a slew of startup biotechnology companies with the lofty aim of developing drugs intended to extend the human life span. Specifically, he wants to create a pill that could simultaneously combat Alzheimer's disease, cancer, diabetes and heart disease to ensure that people live longer, healthier lives.
Sinclair is at the forefront of research investigating a chemical called resveratrol, a compound found in such plants as grapes and cocoa, that works by activating SIRT1, a protein believed to play a role in regulating life span in animals. The research has been controversial, with some scientists saying such an anti-aging elixir has been overhyped. But Sinclair is forging ahead with his research and studying other molecules that might combat diseases associated with aging. A new study by Sinclair and colleagues in the European Heart Journal details how SIRT1 might also be involved in cardiovascular disease. Sinclair talked to The Post recently about the future of aging.
Q; When did you come to the conclusion that aging is a problem that can and should be solved?
A: When I became interested in it as a career, I was in the middle of doing my Ph.D in molecular biology and my mother contracted lung cancer. My mother survived for another 20 years.
So after that, I wanted to make a difference in medicine. I thought that tackling aging and the mechanisms that promote life would be worth figuring out. I wanted to learn why it is that some people are healthier than others and why some people live to 110 and others only to 60 or 70.
Q: Most people don't like to think or talk about aging. How do you want to change that?
A: Well, first of all, I would love for the U.S. Food and Drug Administration to regard aging as a condition that's worth treating. The reason is that aging is a decline in function. That, to me, is exactly what a disease is. Unfortunately, because aging is so common and natural, we tend to think of it as destiny or something we should accept. But over the last 300 years, we've been fighting diseases that cause us to suffer. Until very recently, we thought that we should only tackle one disease at a time, whereas what I would like is for the FDA and the general public to appreciate that we now have the technology to prevent multiple diseases at once.
Q: How has studying the aging process made you think differently about how you plan to age?
A: I have been testing molecules on myself, such as resveratrol. I monitor my own body reaction to that. I have done that for over a decade now. My mother, father and wife have also been taking molecules that we've been discovering. My brother recently went on resveratrol, too.
Q: What is the ultimate goal with your aging research?
A: The ultimate goal is to have a pill that can prevent or reverse all diseases of aging. The major diseases that I'd like to tackle are heart disease, diabetes, Alzheimer's and cancer. I want to reduce those diseases by 10 percent. Eventually, I'd like to reduce diseases of aging by 50 percent or more in the general population.
Q: Will things like exercise and a good diet still be important even if a pill exists to prevent age-related diseases?
A: Yes, exercise and diet will be important. Our studies show that the drugs will work even better if you're already healthy. In an experiment we conducted with mice, a healthy diet plus resveratrol was the best combination. Resveratrol had a decent benefit when the mice were obese and sedentary. The mice that were fed a lean diet and resveratrol lived significantly longer than other treated mice as well as those that had no healthy diet and no resveratrol. So resveratrol is not an excuse to be lazy or eat whatever you want.
Q: How much exercising do you do? And what about your diet?
IA: work out in a gym each week, but more exercise would be good. I used to be on a tofu and fish diet to mimic the Okinawans, who live the longest, but with the arrival of kids that went out the window. The best thing I've done is to give up desserts at 40.
Q: Do you drink a lot of wine or eat a lot of grapes to get resveratrol?
A: You would need to drink hundreds of glasses of red wine a day.
Q: Is it possible to consume high enough levels of resveratrol in food for health benefits?
A: No. There is only a few milligrams of resveratrol in a glass of red wine, and the doses required are in the hundreds of milligrams. I take resveratrol as a pill with breakfast — 1,000 milligrams, a spoonful on yogurt.
Q: How old do you see yourself living?
A: I'd like to see what humanity achieves 500 years from now, but without successful pharmacological intervention I doubt I will make it past 85 with the sub-par genes I know I've inherited.
Q: Do you think Alzheimer's, heart diseases or other age-related diseases can be completely eliminated?
A: We will probably still die from those diseases eventually. What we want to do is stretch out the healthy period. Ideally, the end of life would be shorter, but it would still be caused by one of those diseases, a heart attack or a stroke.
Q: What would a world in which people age better look like?
A: Children born after 2050 can expect to live to 100. People will be healthy throughout most of their lives. They'll be 80 years old and still active; they could play tennis and hang out with their grandchildren. You see some people like that now, but we can expect the majority of people to look like that when these medicines are available. What that also means is that the people who are now living to 100 could instead live to 120 or 130. I think by the end of the century, people could live to 150 because there's going to be a combination of research that will lead to pills we could start taking at the age of 30 to boost the body's defenses against diseases and age. The combination of drugs and regenerative medicine has huge potential for age extension. My work is trying to keep the body healthy for as long as it can by activating the body's defenses, and other scientists are working on technology to grow and replace organs.
Q: How soon do you think we will have an approved pill that could extend life span?
A: In the aging field, we're starting to organize a study to see if we can expand human life span with a drug. There are at least three other molecules that we'd like to try after that. We've had discussions with the FDA regarding aging as a disease and if we could start a clinical trial. We're in the beginning stages, but it looks like the FDA will approve a clinical trial for aging.
Mullin is a freelance science writer.
