Natural compounds could revive older muscles

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As our years add up, strength and muscle mass decline.

University of Iowa scientists recently discovered the first example of a protein that causes muscle weakness and loss during aging. The protein, ATF4, is a transcription factor that alters gene expression in skeletal muscle, reducing muscle protein synthesis, strength, and mass.

The UI study also identifies two natural compounds—ursolic acid from apples and tomatidine from green tomatoes—that reduce ATF4 activity in aged skeletal muscle. The findings were published online Sept. 3 in the Journal of Biological Chemistry.

In the study, mice with age-related muscle weakness and atrophy were fed diets lacking or containing either 0.27 percent ursolic acid, or 0.05 percent tomatidine, for two months. The scientists found that both compounds turn off genes that are turned on by the transcription factor ATF4. This action increased muscle mass by 10 percent, and more importantly, increased muscle quality, or strength, by 30 percent.

These results led researchers to engineer and study a new strain of mice that lack ATF4 in skeletal muscle. Like old muscles that were treated with ursolic acid and tomatidine, old muscles lacking ATF4 were resistant to the effects of aging.

Emmyon Inc., a company founded by senior study author Christopher Adams (’99 MD/PhD), UI professor of internal medicine, is working to translate ursolic acid and tomatidine into foods, supplements, and pharmaceuticals that can help preserve or recover strength and muscle mass as people grow older.