October 31, 2006
AN INTERESTING STORY ON LONGEVITY RESEARCH in the New York Times starts off with calorie restriction but quickly moves on to the larger topic:
Recent tests show that the animals on restricted diets, including Canto and Eeyore, two other rhesus monkeys at the primate research center, are in indisputably better health as they near old age than Matthias and other normally fed lab mates like Owen and Johann. The average lifespan for laboratory monkeys is 27.
The findings cast doubt on long-held scientific and cultural beliefs regarding the inevitability of the body’s decline. They also suggest that other interventions, which include new drugs, may retard aging even if the diet itself should prove ineffective in humans. One leading candidate, a newly synthesized form of resveratrol — an antioxidant present in large amounts in red wine — is already being tested in patients. It may eventually be the first of a new class of anti-aging drugs. Extrapolating from recent animal findings, Dr. Richard A. Miller, a pathologist at the University of Michigan, estimated that a pill mimicking the effects of calorie restriction might increase human life span to about 112 healthy years, with the occasional senior living until 140, though some experts view that projection as overly optimistic.
According to a report by the Rand Corporation, such a drug would be among the most cost-effective breakthroughs possible in medicine, providing Americans more healthy years at less expense (an estimated $8,800 a year) than new cancer vaccines or stroke treatments.
That’s absolutely right. Calorie restriction is unlikely to work in humans — and I’m not sure it’s worth it anyway — but drugs that mimic its effects are another thing entirely.
Of course, some critics say that this is going for the low-hanging fruit when we should be working on stopping or reversing aging, not just slowing it down. I figured I’d find a discussion of that issue over at FightAging.org, and sure enough I was right. I think, though, that it’s nice to see that people are getting interested in this field at all, and if there’s a prospect of antiaging drugs that work better, lots of companies will jump on it as the financial incentives are huge.
Still, some experts on aging doubt that enough is known about CR to guide the development of drugs that mimic its effects. “We know a lot about CR’s effects,” says Edward Masoro, a leading gerontologist. “But what bothers me is that I don’t think we’ve figured out CR’s basic mechanism yet.”
Dr. Sinclair’s idea that resveratrol mimics CR has come under heavy fire. His main adversaries are two researchers who used to rub elbows with him when they all studied together with MIT’s Dr. Guarente. The skeptics maintain that resveratrol’s mode of action is still murky; instead, they are looking at other mechanisms that may account for how CR works.
The resveratrol doses used in the life-span-extension studies in animals were far higher than the amount people can get by drinking wine — they were roughly equivalent to hundreds of glasses a day. Resveratrol is available as a dietary supplement, but to replicate the doses used in the studies, a person would need to take scores of pills a day. (Sirtris says it is developing prescription drugs that work like resveratrol but are hundreds of times more potent.) The dietary supplements haven’t been tested in clinical trials, so their efficacy isn’t proven, nor is it clear what dose might make people live healthier or longer. And although they seem safe at modest doses, megadoses may not be.
Nevertheless Dr. Sinclair, a 37-year-old Australia native, thinks taking small doses over time may yield health benefits and has been taking the supplements for three years. . . .
Sirtris, the company Dr. Sinclair co-founded, says it has made progress. Test-tube and animal studies suggest that its early-stage drugs may help treat various neurological killers as well as diabetes, says Dr. Westphal. The company plans soon to begin testing a drug in people with MELAS syndrome, a rare metabolic disorder that afflicts youngsters with potentially fatal brain and muscle deterioration.
At a recent meeting on aging research, a Sirtris scientist reported that SIRT1-activating compounds, including resveratrol, dramatically lowered blood levels of glucose and insulin in mice that get diabetes on high-fat diets, as well as helped to keep their weight down — just as CR does.
It’s easy to get overexcited about early research, but let’s hope that this succeeds. The economic boost of extending people’s healthy lifespans would be huge, and of particular value to countries with big unfunded pension obligations and low birthrates, which is most industrial countries. Such research is likely to be politically popular with an aging electorate, too. (But note the usual man-wasn’t-meant-to-do-this line from Leon Kass at the end of the NYT story.)
I’ve got a pretty lengthy discussion of the topic in An Army of Davids, and I’ve also addressed it in articles here and here, and in a lengthier review essay here. It’s a huge issue for coming decades.