Dr. Masoro led a study in the 1970s that narrowed the search for the fountain of youth. His team found that it could extend life spans and reduce the incidence of disease in rats by manipulating their diets.
Researchers divided the rats into two groups. One group ate at will; the second got a balanced but restricted diet that was about 40 percent less than normal intake.
Rats on the restricted diet lived longer, and were less prone to disease. Rats eating at will lived up to 32 months, but their diet- restricted counterparts lived up to 48 months. In addition, the diet- restricted rats seldom contracted heart or kidney disease, and the onset of cancer came much later than for the other rats.
The research continues even today at the Health Science Center and other institutions trying to unravel the mystery of aging.
Researchers regard diet restriction as a technique to find answers to the mystery of aging. No one is recommending it as a prescription for longevity in humans.
"It's worked on every species it's been tried on so there's no reason to think it won't work on humans, but the important thing is it extended productive time so the animals are healthier when they're older," said Roger McCarter, PhD, professor of physiology.
Dr. Masoro's research has spun off several related studies at the Health Science Center since his work began in 1975.
"I didn't foresee how the research would snowball at our institution," Dr. Masoro said, "but it was clear to me that aging was going to be important to biological research even at that time because of the sheer increase in the aging population."
Diet restriction modeled after Dr. Masoro's examples is being studied in primates at the University of Wisconsin and the National Institute on Aging. On campus, Byung Pal Yu, PhD, one of Dr. Masoro's original collaborators, is studying the role of free radicals, byproducts from the body's conversion of sugar and oxygen into energy. The neuroendocrine aspect of aging is being examined by Dike Kalu, PhD, and James Nelson, PhD, physiologists.
"The work by Dr. Masoro and his colleagues is the gold standard in research on the biology of aging," said T. Franklin Williams, MD, former director of the National Institute on Aging. "He and his colleagues are at the forefront in research on diet, food content and survival."
Dr. McCarter has explored the connection between diet and exercise. In earlier studies, diet-restricted rats routinely showed great stamina and ran four to five miles a day on exercise wheels.
"It's like a 70-year-old man or woman running perhaps 40 to 50 miles a day," Dr. McCarter said.
Dr. McCarter determined that exercise did not account for the rats' longevity, but it seemed to fight disease. Exercising rats lived longer than the others, but maximum life spans were the same.
The research helped eliminate one suspect in aging - the pace of metabolism. "It turns out that your body mass adjusts to the input of calories if you stay on a restricted diet for a very long time. So the theory that dietary restriction slows down aging by slowing the metabolic rate is just not true," he said.
Metabolism remains a suspect, but for different reasons.
Dr. McCarter suspects that metabolism sets off reactions that promote aging. Diet-restricted rats maintain low glucose and insulin levels, which reduce the reactions, he said.
"We need food energy to live, but this fuel is highly reactive by its very nature. In the body it undergoes side reactions that accumulate with time and cause destructive changes. We need food energy to live, but by the same token it may be killing us," he said.
Dr. Yu is examining free radicals, oxygen molecules created by metabolism that can damage cells. He has found less oxygen damage to cells in food-restricted rats than their free-eating counterparts.
What does Dr. Masoro expect to see in the next 20 years?
"We will understand how food restriction works, and we will have pharmacological products to mimic its effects. We will then look at other ways to view the basic nature of the aging process, and the ways to reverse many of its ill effects. As a society, we are likely to discover the value of age as more individuals are kept healthy and productive. We may even see greater scientific progress due to the increase in the productive years of older scientists," he said.