A Protein That Causes Muscle Loss

By Sondra Forsyth

Researchers have discovered that a protein causes muscle weakness and loss during aging, according to a news release from the University of Iowa.

The protein, ATF4, alters gene expression in skeletal muscle, causing reduction of muscle protein synthesis, strength, and mass. The Iowa study also identifies two natural compounds, one found in apples and one found in green tomatoes, which reduce ATF4 activity in aged skeletal muscle.

The findings, which were published online in the Journal of Biological Chemistry, could lead to new therapies for age-related muscle weakness and atrophy.

“Many of us know from our own experiences that muscle weakness and atrophy are big problems as we become older,” said Christopher Adams, M.D., Ph.D., professor of internal medicine in the UI Carver College of Medicine, and senior study author. “These problems have a major impact on our quality of life and health.”

Previously, Adams and his team had identified ursolic acid, which is found in apple peel, and tomatidine, which comes from green tomatoes, as small molecules that can prevent acute muscle wasting caused by starvation and inactivity. Those studies set the stage for testing whether ursolic acid and tomatidine might be effective in blocking the largest cause of muscle weakness and atrophy: aging.

In their latest study, the investigators found that ursolic acid and tomatidine dramatically reduce age-related muscle weakness and atrophy in mice. The size of those effects suggest that the compounds largely restored muscle mass and strength to young adult levels.

“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,” Adams says. “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.”