A View from David Ewing Duncan
Longevity Pill Tested in Humans
Sirtris Pharmaceuticals announces that its souped-up version of resveratrol has passed early tests in humans.
What if I told you there was a pill that slows aging and allows you to live a healthy life to age 100?
Such a pill may exist right now. It’s being tested in people in very early-stage human clinical trials. Today, the company making the pill, Sirtris Pharmaceuticals, announced its findings from preclinical testing in cells and animals, and also from tests conducted on 85 male volunteers this summer.
The verdict: so far, the pill works, although it will be years before we know how well it works, or if it can actually extend the life span of people in the same way that it has bumped up the life span of mice.
Speaking today at the Annual Metabolic Diseases Drug Discovery and Development World Summit in San Diego, Sirtris’s senior director of biology, Jill Milne, announced that the drug, SRT501, reduces glucose and improves insulin sensitivity in animal and in vitro studies of the drug’s effect on type 2 diabetes. In people, the drug was tested for dose, safety, tolerability, and pharmacokinetics–that is, how well the drug was absorbed, distributed, metabolized, and removed from the body.
Phase 1b trials are already under way to test safety and pharmacokinetics on patients with type 2 diabetes. Later-phase trials will test to see if the drug actually works in diabetics.
SRT501 is a proprietary chemical developed by Sirtris that’s based on the naturally occurring resveratrol that company cofounder David Sinclair of Harvard University has been studying for its effects in extending life span in a number of organisms, including yeast, flies, and mice. Last year, Sinclair created a sensation when he published a paper in Nature detailing how mice on a high-fat diet that were fed large doses of resveratrol were as healthy as mice on a regular diet. Resveratrol also sharply extended life span, produced positive changes in insulin sensitivity and other diabetes-preventing mechanisms, and increased energy production in cells. The mice were given very high doses of resveratrol–22 milligrams per kilogram of weight. In comparison, a liter of red wine delivers 1.5 to 3 milligrams. To match the results in the mice, a 150-pound human would need to drink 750 to 1,500 bottles of wine a day.
Sinclair says that SRT501 is a thousand times more potent than naturally occurring resveratrol, which gives it the same punch as the resveratrol in all those bottles of wine.
Sinclair believes that resveratrol activates a gene called SIRT-1, which is associated with the regulation of life span in several animals. This contention is disputed by some critics: they argue that the mechanism by which resveratrol works is still poorly understood.
Because humans are so long-lived, SRT501 can’t be easily tested for longevity in humans–nor does the Food and Drug Administration recognize “increased life span” as an allowable indication for an approved drug. This is why Sirtris is testing SRT501 for diseases related to aging, such as type 2 diabetes. However, should the drug be approved for diabetes, it will undoubtedly be used to extend life span by many people without diabetes.
The drug still has years of testing to go and faces many hurdles. It may not work. But if it does, the consequences will be profound. For instance, it will mean that more people will be alive on the earth. Age 90 will be the new 70, and 70 the new 50, with profound impacts on everything from social security to retirement age. It may also mean fewer people with diabetes, Alzheimer’s, and some cancers.
Can one pill do and cause all that? Critics have long said no–that such a compound will not work in humans. But they also said it wouldn’t work in mice–until it did work. (At least in fat mice.)
So let’s sip some pinot noir and wait for more results from Sirtris. After all, we’re not getting any younger.
Look for my profile of longevity researcher David Sinclair in the September/October issue of Technology Review.
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