A restricted branched-chain amino acid diet has sex-specific lifespan benefits in mice

Dudley Lamming, PhD, associate professor, Endocrinology, Diabetes and Metabolism, and first author of the study, Nicole Richardson, PhD look over data

A recent study in Nature Aging from the laboratory of Dudley Lamming, PhD, associate professor, Endocrinology, Diabetes and Metabolism, found evidence that a diet restricting branched-chain amino acids (BCAA) can extend the lifespan and increase metabolic health in mice.

Protein-restricted diets have been shown to promote health and longevity in many species. Dietary protein is composed of amino acids; nine of these amino acids, including the BCAAs, are essential in the diet. The three BCAAs are leucine, isoleucine and valine, and are linked to insulin resistance in mice and humans. To better understand the contribution of the BCAAs to the beneficial effects of low protein diets, Dr. Lamming and colleagues reduced the dietary level of the BCAAs in the mice diet by two-thirds.

This low-BCAA diet was fed to progeroid mice, which are very short lived and display characteristics of aging like a hunched back and grey hair, as well as to standard (wild-type) lab mice.

The team found that restricting BCAAs extended the lifespan of male and female progeroid mice. When they restricted BCAAs in standard wild-type mice starting in middle-age, both types of mice experienced improved health and reduced frailty, and female mice had reduced rates of cancer, but they didn’t live longer.

But, when mice were fed this diet from early on in life, instead of at the end of life, the findings were different. Male lifespan was extended by 30%, and they experienced less frailty. However, no difference in lifespan or frailty was shown in female mice when fed this diet from early on in life. Additionally, the team found that the low-BCAA diet increased metabolic health by improving body composition, and better controlling blood glucose.

Dr. Lamming explained that this is the first time that restriction of BCAAs have been shown to extend lifespan and reduce frailty. Previous research has shown that low-protein diets can extend male lifespan, but there’s has been little research done on the specific role of the BCAAs, and little work done using female mice.

“This is the first time we showed that a low BCAA diet improves metabolic health in female mice, and the first time we showed this in middle-aged and old mice,” Dr. Lamming said. “We think that protein or BCAA restriction, at least to this degree and started when young, doesn’t work to extend the lifespan of females,” Dr. Lamming said.

The next steps in this line of research included understanding which specific BCAAs, leucine, isoleucine or valine, is responsible for the improvements in health and longevity.

These findings demonstrate the intersection between aging and nutrition, and can be further looked at as a method for preventing and intervening in age-related disease. “Between this [study] and other work we’ve published, we believe that reducing branched-chain amino acids are really key to promote healthy aging, at least in mice,” Dr. Lamming said.

This work was supported in part by a grant (PRF2015-61) from The Progeria Research Foundation, by grants from the NIH (AG041765, AG050135, AG051974, AG056771 and AG062328), by a Glenn Foundation Award for Research in the Biological Mechanisms of Aging and by funding from the University of Wisconsin-Madison School of Medicine and Public Health and Department of Medicine.

Banner: Dudley Lamming, PhD, associate professor, Endocrinology, Diabetes and Metabolism, and first author of the study, Nicole Richardson, PhD, look over data. Credit: Clint Thayer/Department of Medicine.