Using clues from a geriatric laboratory mouse named Freddy, scientists have discovered another benefit of the only proven technique for extending the life expectancy of mammals.
They also have found that the technique-calorie restriction-prevents age-related damage to nerve cells in the brains of animals.
“It is possible that something fairly simple can be done to alter the aging process, to slow the clock-the timing mechanism-that makes all kinds of animals age,” Dr. David E. Harrison says. “But the fact is that we don’t know enough about the basic aging process to say whether it will be calorie restriction or something else.”
Harrison is a scientist at the Jackson Laboratory at Bar Harbor, Maine, who conducted the mouse research with Dr. Roderick T. Bronson of Tufts University and the U.S. Department of Agriculture’s Human Nutrition Research Center on Aging in Boston. Both emphasized that the clues about calorie restriction, although tantalizing, are not firm enough for application to humans.
Indeed, they cited conflicting evidence on whether calorie restriction would be beneficial or harmful to people.
As the term suggests, calorie restriction involves reducing the amount of calories consumed. In studies with lab mice, calorie-restricted animals usually get diets containing one-third fewer calories. They eat the diet for a lifetime, beginning after weaning, and live about twice as long as mice on a conventional diet.
Calorie restriction and aging have become the focus of a major federal research program, sponsored by the National Institute on Aging and conducted at a dozen medical centers across the country.
Scientists are using mice and rats in the studies because the animals are cheap, easy to handle and yield quick results. Mice, for instance, age about 30 times faster than humans, reaching the equivalent of old age in two years.
Other calorie-restriction studies are under way in animals more closely related to humans, including dogs and monkeys. All are part of an effort to understand factors that control aging, including those that might be manipulated to increase human longevity.
Bronson and Harrison trace their new research to the late 1980s and the death of a renowned laboratory mouse named Freddy. Freddy was the Methuselah of mice. Eating a calorie-restricted diet, Freddy lived 1,742 days – nearly five years – which Bronson said made him the oldest known lab mouse in the world. His age equivalence in human terms: 140 years.
While studying Freddy’s brain tissue, scientists also noted an unusual accumulation of certain abnormal cells, never before observed in the same region of the brain. They verified that similar changes occur in other strains of laboratory mice, and they began using the changes as a “marker,” or indicator, of the effects of aging.
In the latest research, they established that mice fed a calorie-restricted diet have healthier brain tissue than those on a conventional diet, with a 30 percent reduction in the abnormal cells.
Bronson and Harrison are trying to understand how calorie restriction works to keep brain tissue healthier and to prolong life span in animals and what the implications may be for human aging.
They emphasized that calorie restriction in laboratory animals is effective only when it begins in infancy and continues life-long. Elderly humans, far from needing calorie restriction, typically need to eat more, according to Bronson. He said that many older people have poor appetites and eat too little. Some unknowingly starve themselves, with inadequate intake of calories and other nutrients, complicating their health problems.
Harrison is optimistic about an eventual discovery of the control mechanisms for human aging. He said that a relatively small number of factors may be involved, such as a timing mechanism that can be slowed by dietary changes or other factors.
