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Calorie Restriction a Possible Antidote to Aging and Disease

Could any health topic be hotter than aging? Signs are everywhere that the famously self-obsessed Baby Boom is hitting its Medicare moment.


Turn on the television and you'll see Suzanne Sommers telling a credulous Oprah about her 60-pill-a-day and estrogen-injection regime. On another channel, there's Morley Safer of the venerable "60 Minutes" extolling the anti-aging properties of red wine. Boomers' drugs of choice have become Viagra and phytoestrogens.


Wander into the office of University of Wisconsin School of Medicine and Public Health (SMPH) anti-aging researcher Richard Weindruch, PhD, and you'll see the walls lined with celebrity shots, including Alan Alda, who interviewed Weindruch for a show on Scientific American Frontiers called "Fat and Happy."


rhesus monkeys
Canto, 27, at left, is on a calorie-restricted diet, while Owen, 29, eats whatever he wants.
Weindruch, professor of medicine, is having his own celebrity year. The "60 Minutes" crew came to film his troop of aging rhesus monkeys for a piece on the anti-aging properties of calorie restriction and a substance found in red wine called resveratrol. He and other international aging researchers received cover story treatment in the German magazine Geo Wissen.


He published yet another major paper in Science in July showing that the monkeys on the calorie-restricted diet were looking so good that Suzanne Sommers might reconsider her methods.


And soon, Weindruch will trade his slightly grungy basement office in the William S. Middleton Memorial Veterans Hospital for Lake Mendota views from the seventh floor of the sparkling new Wisconsin Institutes for Medical Research.


Pioneering the Study of Aging


All of this seems deserved, because Weindruch, 59, was studying aging long before aging was cool.

Back in the 1970s when Weindruch first joined the University of California-Los Angeles (UCLA) laboratory of researcher Roy Walford, MD, aging was considered about as exciting a field as watching paint dry.


"Aging was a sleepy discipline back then,'' Weindruch says. "Roy was one of just a handful of people in the country focusing on the biology of aging."


Today the effects of aging are being studied in more than 300 laboratories. Weindruch's own interest in the science of aging began when he earned bachelor's and master's degrees in biology from the University of Illinois and went on to the Northwestern University School of Dentistry. There, he quickly discovered he wasn't interested in spending his life peering into people's mouths.


"I liked the basic science, but when it came to clinical dentistry, I found myself skipping school and going to Cubs games instead,'' he says.


In 1974, he left dental school and returned to his native Rock Island, Illinois, to work in a warehouse and apply for graduate school. He was accepted into the UCLA pathology program, where he met his mentor.


Walford is a story in himself. As a medical student he figured out how to beat the system in a Nevada casino. Before the casino caught on, Walford won enough to pay for medical school, buy a boat and sail around the world.


As Walford's graduate student, Weindruch went from the warehouse to Walford's Venice Beach parties, which featured Hollywood guests such as counterculture guru Timothy Leary.


In the laboratory, Weindruch and Walford were intrigued by a 1930s study led by Clive McCay, PhD, of Cornell University, which found that laboratory rats kept on a severely reduced-calorie diet lived almost twice as long as expected, as long as they had proper nutrients. They duplicated and built on these results in a series of studies showing that mice also looked younger, were more active and showed delays in age-related diseases.


Their first really big paper together, published in Science in 1982, showed that even middle-aged mice benefited from going on a restricted diet.


After earning his doctoral degree, Weindruch spent another decade at UCLA working with Walford on a series of studies as well as the book "The Retardation of Aging and Disease by Dietary Restriction."

Walford practiced what he preached. He limited himself to so little food that his weight dropped to 130 pounds. A photo of him in Weindruch's office shows Walford looking like a pale wraith after two years of living inside the Biosphere 2 in the Arizona desert. Walford was the crew's medical doctor, and the photo shows Weindruch talking with him via telephone.


After leaving UCLA, Weindruch spent three years at the National Institutes of Health, learning what made a successful grant application, before he was recruited to UW-Madison in 1990. This is where he began studying monkeys, to see if the anti-aging results in mice could be duplicated in primates.


Rhesus monkeys live up to 40 years, with a median life span of 27 years, so Weindruch's monkeys are only now showing the anti-aging effects of calorie restriction. Howard Hughes Investigator Andy Dillin, PhD, of the Salk Institute — who studies aging in a species of roundworm that goes through its lifecycle in a matter of weeks — once introduced Weindruch as "the most patient researcher in the world."


Clear Effects of Calorie Restriction


But roundworms will never be able to dramatize the effects of aging to the lay public.


The monkey photo that accompanies this feature — and that appeared in the latest Science article and a New York Times page-one story — show a difference anyone can see. On the right, a monkey that ate all it wanted looks gray and weather-beaten — the monkey version of Brett Favre. On the left, a restricted diet produces a healthier-looking monkey, with glossy hair and a younger face — a monkey Tom Brady. But unlike the NFL quarterbacks, these monkeys are almost the same age.


At least as stunning are the views inside the monkeys' brains. Scans by School of Medicine and Public Health neuroscientists showed that the brains of the Brett Favre monkeys are shrinking, but those of the calorie-restricted Tom Brady monkeys are not.


Weindruch and co-author Ricki Colman also showed in the Science paper that the restricted diet reduced cancerous tumors, cardiovascular disease and diabetes. Half of the monkeys that ate freely have died; 80 percent of the calorie-restricted monkeys are still alive.


So why don't we all just start living on 1,000 calories a day? Because it's difficult.


Weindruch, who briefly tried calorie restriction himself, says, "I think the odds of millions of people adhering to a calorie-restricted diet are zero."


But a few hardy people have adopted a lifestyle they call calorie restriction with optimal nutrition (CRON). About 30 of these so-called CRONies volunteered to be studied at Washington University. Weindruch and his colleagues are using their genetic techniques to study changes in the activity of the CRONies' genes.


"We think these genes hold the secret to how calorie restriction affects the aging process,'' Weindruch says.


The scientists are also looking for substances — in addition to resveratrol — that can mimic the anti-aging effects of calorie restriction without the diet.

Aging Americans may raise a glass of red wine to the hope that research will show a way for them to have their cake-and age gracefully, too.


By Susan Lampert Smith

This article appears in the summer 2009 issue of Quarterly.

Date Published: 09/28/2009

News tag(s):  quarterlyquarterlysummer09

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Calorie Restriction a Possible Antidote to Aging and Disease

Last updated: 10/07/2009
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