Calorie Restrictors Stay Hungry in Hopes of Living Longer

In mice, flies and monkeys, that is.

"Calorie restriction works in the lower organisms, we know," Bauer says. "But with humans it's anybody's guess so far."

The best guess in the scientific community is that starting a program of calorie restriction in your thirties might add two years, says Bauer. "If you start in your forties, it's six months. Start later than that, it's negligible. It could be a few extra weeks."

Yet other researchers seriously doubt the health and longevity benefits of calorie restriction for humans. They say it affects fertility and sometimes causes brittle bones. Animals put on CR early in life are smaller in adulthood. Even devoted human followers of CR complain of cold hands and sniffles that never go away.

So why all the interest in calorie restriction now? What Bauer and other researchers know for sure is that there is a genetic component to the "calorie restriction response" in lab animals, including fruit flies, that is probably similar in humans. Given less food than the body thinks it needs, there is a "switch" that goes on, says Bauer, sending a message to the body's metabolic functions.

"If we could develop switches in the body to turn on and off the calorie restriction response, we could extend life expectancy," Bauer says. That's what he's looking for in his fruit flies — the "switch" in their genetic makeup that will give the order to their bodies to be healthy and live longer, no matter how much they eat.

And if they find the switch, says Bauer, scientists want to develop a drug that will activate that genetic on-off mechanism to mimic the health effects of calorie reduction without requiring a drastic change in diet. That will be the magic pill. One that fools the human body's metabolism and slows the aging process. One that allows people to remain disease-free without having to eat smaller meals.

And here's the good news: Some scientists think they've found it.
_____________________

It's called resveratrol. It's a natural substance available right now for a few cents a dose in health food and vitamin stores. Sold under various retail names, it's classified as a food supplement in the "antioxidant" category and is not regulated by the Food and Drug Administration.

It's been proven effective already on fat mice in a University of Pennsylvania study published in 2006 in the premier science journal Nature. Mice raised on the equivalent of a cheeseburger-and-fries diet were given resveratrol and compared to mice fattened without the supplement. The study found that the fat mice on resveratrol didn't lose weight, but were healthier than the other mice. They also lived longer. In a French study, resveratrol-fed fat mice outran skinny ones in treadmill tests and built up healthy muscle even without exercise.

"Resveratrol could be the get-healthy drug," SMU's Bauer says. "It could be the miracle drug."

And Big Pharma doesn't even control it (yet). Medical and pharmaceutical interest in resveratrol has boomed over the past decade. Found naturally in certain vines, pine trees, red grapes, chocolate and peanuts, it is a chemical polyphenol that helps plants fight off drought, fungi, parasites and other external stressors. In the early 1990s, chemists looking to find the key to the "French paradox," which allows the French to eat fatty food without getting heart disease, zeroed in on res­ver­atrol, part of the natural chemistry of red wine grapes and the likely reason red wine produced healthy heart effects.

Dozens of studies now have pinpointed the substance as a bonus not only to heart health but to the prevention of Alzheimer's and diabetes, reversals of inflammatory responses to spinal cord injuries, and the prevention and treatment of stroke. Resveratrol is being tested in clinical studies as a natural supplement to chemotherapy and has shown the ability to block cancer cells before they metastasize to bone.

In the most widely publicized report on resveratrol, researchers at Harvard Medical School showed that it mimicked calorie restriction and activated the "longevity gene" in yeast, extending its life span by 70 percent. Harvard professor David Sinclair, one of the scientists on that study, is so confident about the future of resveratrol that he founded a biomedical research company, Sirtris (named for the sirtuin family of enzymes that react to calorie restriction), which focuses on discovering resveratrol-like "small molecule drugs." Sirtris Pharmaceuticals was recently acquired by drug giant GlaxoSmithKline for $720 million.

Creating a synthetic resveratrol, one that can be approved by the FDA (and will be profitable for GlaxoSmithKline), will be one of the biggest medical discoveries since aspirin, Sinclair said in an interview on PBS's NewsHour. "Let's admit that people have claimed that they've had the elixir of youth probably for the last 40,000 or more years. So I don't want to claim that we have the cure for aging, by any means, but it's really clear that modern medicine, modern molecular biology has finally grasped a potential way to manipulate life span and have a dramatic impact on health care."

A pill that diets for you is certainly easier than staying hungry. The question is how much resveratrol, or its derivatives, you'd have to take to get the benefits. In the concentrated version used in lab studies, each dose is about the equivalent of 14 bottles of red wine.