Calorie Restriction Reduces Age-Related Muscle Loss
June 16, 1997
Researchers at UW-Madison have found that limiting calorie intake later in life can stall some of the muscle deterioration that normally accompanies aging.
Reported in the June 1997 FASEB (Federation of American Societies for Experimental Biology) Journal, the research involved age-related fiber loss and enzyme and gene abnormalities in rat muscle.
"We were surprised to find that initiating calorie restriction so late in an animal's life could reduce the muscle changes that occur regularly with aging," said UW Medical School professor of medicine Richard Weindruch. "Age-associated muscle degeneration is seen in most mammals, including humans."
The new findings add to a growing body of evidence supporting significant age-retarding effects of a restricted yet nutritious diet. In addition to extending life span in many animals, calorie restriction (CR) slows down age-related deficits in behavior and learning, immune response, gene expression, enzyme activity, hormonal action, DNA repair capacity, glucose tolerance and rates of protein synthesis.
Weindruch, who co-authored the first text on dietary restriction, an in-depth review article in Scientific American and several reports in other prestigious journals, was the first to show that even starting rodents on a controlled diet in midlife produced longer-lived, healthier animals.
A researcher at the Geriatric Research, Education and Clinical Center at the William S. Middleton Veterans Hospital and UW-Madison, Weindruch and colleague Judd Aiken, associate professor of animal health and biomedical sciences, focused on skeletal muscle in their current study to determine how CR affects age-linked muscle mass loss. Known as sarcopenia, the condition is thought to contribute to physical frailty in older people.
"Laboratory studies by our team and others have shown that CR can reduce the rate of skeletal muscle loss with age, but the exact mechanisms have been unclear," said Aiken.
Some scientists theorize that CR may reduce sarcopenia by influencing mitochondria, cellular energy factories. A restricted diet may lower production of harmful free radicals, which normally result when mitochondria convert oxygen and food to energy.
The UW researchers concentrated on two enzyme problems that usually indicate mitrochondrial defects: "red ragged" fibers (RRFs), which occur with an abnormal accumulation of mitochondria; and COX-negative fibers, or those that lack cytochrome c oxidase. Both RRFs and COX-negative fibers increase with age in some human muscles.
Weindruch and Aiken's team also focused on another potential player in the aging process: deletions in the mitochondrial genome, the complete set of genes pertaining to each mitochondrion. Finally, they examined fibers in specific rat muscles.
Researchers examined muscle tissue from old rats on unrestricted diets, and moderately (35 percent) and highly (50 percent) restricted diets. Young rats on unrestricted diets also were included in the study.
Analysis of the tissue showed that fiber numbers were preserved in the highly restricted, old animals. Muscle from these rats also contained significantly fewer RRFs as well as COX negative activity. What's more, they had significantly lower numbers of mitochondrial gene deletions.
"These findings support the notion that abnormalities in mitrochondrial activity may contribute to sarcopenia," said Weindruch. "CR initiated in late middle age apparently can slow the progression of this pervasive problem."