Why you should care
Because we should be able to feel young even when we’re not.
As a kid, David Sinclair was shocked to discover that all living things grow old and die. Skirting around desert shrubs and acacia trees in the parched Australian bush of Sydney, he would chase after kookaburras, rainbow lorikeets, currawongs and the occasional wallaby, often wondering how these curious creatures stay alive — and why they eventually perish.
That was the jumping-off point for Sinclair’s career. Today, he’s a professor of genetics at Harvard and founder of the Sinclair Lab, where he and his team study the processes that cause age-related diseases. Sinclair aims to develop a drug that will interrupt these processes and, ultimately, find the Holy Grail: a way to reverse aging. If, that is, he can get government approval — and at the moment that’s looking doubtful.
Google “age-related diseases,” and you’ll soon have plenty of reasons to hope he’s successful. Hypertension, cancer, diabetes, dementia and osteoporosis are just five of the umpteen degenerative conditions that threaten your body as you get older. Scientists have made great strides in finding treatments for these diseases, including personalized immunotherapy to fight cancer and developing Bydureon, an injectable anti-diabetic medication. But they’re going about it all wrong, according to Sinclair, because most of the scientific community doesn’t look at aging itself as a disease. “Your doctor should be able to prescribe a drug that would slow or reverse aging,” he says, “the same way he or she would prescribe a drug for high cholesterol.”
Since 2003, Sinclair has been studying the effects of a chemical called resveratrol in mice. It’s found in foods like cocoa and grapes but only in very small amounts. “You’d have to drink 1,000 glasses of red wine a day to get enough resveratrol to have an effect,” says the 49-year-old. Resveratrol activates a protein in the body called SIRT1, which has been linked to longer lifespans in animals. In rodent trials at his pharmaceutical company Sirtris, Sinclair found that some mice given resveratrol lived longer, showed improved heart function and reduced bone loss. His team had begun studying the compound in humans in 2011, but the head of Sirtris at the time, George Vlasuk, disagreed with Sinclair about the merits of resveratrol as a drug and halted all further clinical trials. The difficulty of maintaining a consistent level of resveratrol in the bloodstream, in addition to the fact that it’s a natural substance and therefore not patentable, led Vlasuk to halt further clinical trials.
Although Sinclair still maintains that resveratrol promises to slow age progression, he shifted his focus to boosting nicotinamide adenine dinucleotide (NAD) levels in mice, which also triggers SIRT1 — as well as SIRT2 – 6 proteins associated with longevity. In a study published in the March issue of Cell, his research showed that increasing NAD levels in 20-month-old mice — elderly by rodent standards — had them outrunning 2-month-old mice.
Sinclair is chasing more than a longer lifespan — he wants to increase the number of healthy, mobile and disease-free years we have on Earth.
Sinclair’s team has yet to complete clinical trials, but he and his father have been taking resveratrol supplements for 15 years and NAD boosters for the past 18 months. He reports that his father has no aches or pains and still goes whitewater rafting and mountain climbing: “My father is 70 but feels 30,” he says. As for Sinclair himself, “My physical and mental capabilities are just as good as when I was 20.”
Viewed as something of a misfit scientist in his postgrad days, today Sinclair is one of only 15 global leaders in the field of geroscience, a term coined a decade ago at the Buck Institute for Research on Aging. After receiving his Ph.D. in molecular genetics at the University of New South Wales in Sydney, Sinclair was accepted into MIT’s postdoctoral research program, with the requirement that he provide all his own funding. The Heart Foundation turned him down “because they didn’t think aging was an important field of study,” he recalls. Eventually, he was awarded the Helen Hay Whitney Postdoctoral Fellowship — the first foreigner ever to receive the grant.
At MIT, Sinclair fastened on the reason yeast gets older — his first clue to understanding why living things age — and discovered it had to do with SIRT2 becoming tangled. SIRT2 can be kept untangled through diet and exercise, says Sinclair, but a desire to find a therapeutic treatment drove his next two decades of research. In addition to his work at Harvard, Sinclair has founded a number of biotech companies — Sirtis, Life Biosciences, Jumpstart Fertility, Spotlight Biosciences and more — dedicated to finding an anti-aging drug.
But as it turns out, “aging” is a tricky term for the scientific and regulatory communities to agree on, posing a significant problem for the release of any pharmaceutical treatment. While the National Institute on Aging (NIA) has funded some of Sinclair’s work, they’re cautious about bumping up against regulatory obstacles. The Food and Drug Administration oversees the approvals process of taking a drug to market, and “the FDA does not have criteria for ‘aging’ to clear compounds that might slow the rate of aging in humans,” explains Ronald A. Kohanski, deputy director of the Division of Aging Biology at NIA. Investors are attempting to set those criteria, Kohanski says, but the process has many safeguards in place that could prevent an anti-aging drug from ever being sold legally.
Tristan Edwards, CEO of Life Biosciences, says Sinclair won’t be stopped by regulations. He has worked with the geneticist for two and a half years and is thoroughly impressed by Sinclair’s focus on translating lab discoveries into tangible outcomes. “There’s no doubt in my mind he’ll extend human health span,” says Edwards.
But Sinclair is chasing more than a longer lifespan — he wants to increase the number of healthy, mobile and disease-free years we have on Earth. For his part, Sinclair says he wouldn’t mind enjoying another hundred years or so with his wife and three kids, kayaking every summer near their oceanfront home.
Of course, anyone who invents a way to stop the clock on aging stands to make a fortune. In 2017, the global anti-aging market was worth nearly $325 billion and it’s predicted to hit $429 billion by 2022. But Sinclair is adamant that he’s not motivated by money. “Every day I focus on making medicines that will improve lives,” he says.
Sounds good, as long as time doesn’t run out in his race to vanquish aging.