The protein is called ATF4 and is inhibited by naturally occurring compounds such as Tomatidine (found in green tomatoes) and ursolic acid (apple peel). ATF4 regulates muscle aging as it is a transcription factor that influences the expression of certain genes in skeletal muscle.
“Many of us know from our own experiences that muscle weakness and atrophy are big problems as we become older,” states senior study author Dr. Christopher Adams, professor of internal medicine at the University of Iowa Carver College of Medicine.
Mice were provided with a diet, for two months, that contained either 0.27% ursolic acid or 0.05% tomatidine. The research results revealed that mice whose diets included either of the two compounds, had a muscle mass that increased by around 10% and muscle strength that increased by around 30%; restoring them to levels similar to those observed in young adult mice.
“Based on these results, ursolic acid and tomatidine appear to have a lot of potential as tools for dealing with muscle weakness and atrophy during aging. We also thought we might be able to use ursolic acid and tomatidine as tools to find a root cause of muscle weakness and atrophy during aging,” said Dr. Adams.
Genetically engineered mice without ATF were tested for the impact of ATF4 in skeletal muscle. Muscles that did not contain this protein were resistant to age-related muscle wasting.
“By reducing ATF4 activity, ursolic acid and tomatidine allow skeletal muscle to recover from effects of aging,” Dr. Adams said.
The researchers specify that ursolic acid- and tomatidine-based approaches could possibly be used alone, together, or in combination with physical therapy and other nutritional and pharmaceutical approaches. Further testing in humans is required.
Identification and small molecule inhibition of an ATF4-dependent pathway to age-related skeletal muscle weakness and atrophy, Christopher M. Adams et al., Journal of Biological Chemistry, doi: 10.1074/jbc.M115.681445, published online 3 September 2015.