Is the future thin monkeys or chubby mice? Gerontology is having a productive week, as the results of two anti-aging studies promise greater longevity -- or do they? In one study, researchers fed Rhesus monkeys a reduced calorie (CR) diet to counter the effects of aging. In the other mice were given large doses of resveratrol, a compound found in grape skins and wine, which apparently countered the ill-effects of a high fat diet. Both the mice and the monkeys thrived on their respective regimens.
When researchers reduced Rhesus monkeys' daily caloric intake, allowing the monkeys far fewer food pellets than the animals might have liked, as the animals aged they suffered less arthritis, heart disease, cancer, Alzheimer's diabetes, and Parkinson's than the cohort fed the regular diet. This result isn't surprising. There is well known longevity effect attached to under eating, and mice, rats, fruit flies, roundworms and other species have all taken a turn at proving this theory. But although "systematic under eating", "under nutrition without malnutrition", and "long-term under nutrition" have been around for almost a century, scientists forever hedge when it comes to recommending such a regimen for humans. In April, 1990 the New York Times wrote in "Diet Offers Tantalizing Clues to Long Life":
"initial observations that an extremely low-calorie diet extends life span in animals date back to the 1930's, but they were long shrugged off as mere laboratory curiosities."
In that 1990 article scientists had yet to study monkeys so they warned that people should be careful about under eating:
"..researchers warn against people undertaking an ascetic regimen too hastily. They stress that experimental animals are fed carefully measured and planned menus that are difficult to translate into human fare, and that it is easy to become malnourished."
Despite the warnings, the CR *movement* has gained a dedicated group of followers in the past decade, although certainly hordes of people aren't clambering aboard the semi-starvation bandwagon. New York Magazine offered a a glimpse of the lifestyle of the CR group this week in "The Fast Supper". Between the magazine's profile and the New York Times article, One for the Ages: A Prescription That May Extend Life", you can get a taste of the ascetic lifestyle choices of CR diet adherents.
Newspaper reports about the studies feature pictures of the lab animals in different states of aging, some graceful, posing for photographers next to plates of food and wine. The animals peer out from the pages of the newspaper, as if taunting the reader -- that supposedly brainy human species which spends millions of dollars seeking anti-aging remedies and pursuing immortality yet flirts with mortality incessantly by eating so much as to become quite fat, and ill and decrepit. Acknowledging the sometimes ironic senselessness of it all, nevertheless, one might endure such deprivation -- if it worked.
But even if you're convinced (or not) by CR advocates who say they enjoy their three leaf salads with a spot of dressing and a scallop and if you don't find the gaunt, bony aesthetic off-putting, doctors' conclusions about the diet might dissuade you from forgoing today's breakfast, lunch and dinner. Tuesday's
"calorie restriction is doomed to fail, and will make people miserable in the process...have you ever tried to go without food for a day"?
Never mind those humans who find this diet quite rewarding, or that decades of research shows that it (more by less) works. Red wine and resveratrol, by comparison, seem to have a more optimistic future -- at least according to the pundits. In 1990-1991 French researchers and scientists at Cornell found that resveratrol might lower cholesterol. People cheered the idea that red wine might actually be "healthy", although scientists coached "moderation". In the current study, mice who were fed large doses of resveratrol and a high fat diet somehow weren't afflicted with heart disease, diabetes, and liver damage. (Interestingly though, cholesterol levels remained high.)
The resveratrol researchers write that the effect of the chemical was similar to calorie reduction and in fact shared 19 pathways, including increased insulin sensitivity and increased hepatic mitochondrial number. They report that it reversed the effects of the unhealthy diet and put the mice who took ample doses of the compound on par with the regular diet control mice. The principle author, Dr. David Sinclair, of Harvard University and Sirtris Pharmaceuticals Inc.(a company with a stake in the research) says that although the mice are chubby, their organs looked younger than the control mice.
The journal Nature, which published the resveratrol paper, was cautious about the results and about extending these results to humans. The mechanism of resveratrol's action aren't precisely known (or published), its safety is untested, and the study used a relatively small sample size of mice. Scientists didn't test whether the chemical could reverse previous liver damage since the mice always took the the chemical. The paper's author thinks that resveratrol may act on SIRT1, as it does in vitro, but that's still speculative. Despite the caution, Nature briefly dares to indulge in cavalier bursts of enthusiasm such as, "of course, the mechanism isn't so important if the drug works." The New York Times notes optimistically:
"very large daily doses of resveratrol could offset the unhealthy, high-calorie diet thought to underlie the rising toll of obesity in the United States and elsewhere, if people respond to the drug as mice do".
Both the mice and the monkeys lived longer lives, but if humans get to pick their poison, we could bet which path will appeal to the most people. It's clearly cheaper to just forgo eating (the CR method). But if people could live a gourmand's life and supplement their gluttony with pills that counteracted the results of overindulgence, we think they might prefer that route. If they could preserve normal physiological functions but not sacrifice that burger, those fries, that croissant, then the popularity of Sirtris Pharmaceutical pill would prevail. Unfortunately, one can't get the same effect from wine -- it would take excessive amounts to get the dose of resveratrol that the mice were given, but you can ignore that you now know that, and just drink wine "because of the resveratrol".
