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Scientists Discover Cause Of and Potential Treatment for Muscle Weakness and Loss Due To Aging

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Aging is one of the inevitable facts of life. As we age, we lose our vitality, strength and muscle mass. However, why our muscles become weak with increasing age is still a mystery. Scientists at the University of Iowa have unraveled the mystery through their recent study. They have discovered the first example of a protein that causes muscle weakness and loss during aging.

The findings of the study were published online recently in the Journal of Biological Chemistry.

The protein known as ATF4 is a transcription factor which changes gene expression in skeletal muscle which in turn causes reduction of muscle protein synthesis, strength, and mass. This finding is significant as it can be instrumental in leading to new therapies for age-related muscle weakness and atrophy. Scientists working on this study have also discovered two natural compounds, one found in apples and one found in green tomatoes, which can lower ATF4 activity in aged skeletal muscle.

Christopher Adams, MD, PhD, UI professor of internal medicine and senior study author said that it is known that muscle weakness and atrophy are big problems as we get older and these problems can have a big impact on the quality of our lives and overall health.

In a previous study, Adam and his team had identified ursolic acid “ a compound found in apple peel, and tomatidine, which is available in green tomatoes, as small molecules which can be helpful in preventing acute muscle wasting caused by starvation and inactivity. Those studies came in really handy to set the stage further and it lead to the testing if ursolic acid and tomatidine are effective in blocking the largest cause of muscle weakness and atrophy: aging.

Adam's team carried out their experiments on mice and found very encouraging results. It was found that ursolic acid and tomatidine dramatically reduce age-related muscle weakness and atrophy in mice. Elderly mice with age-related muscle weakness and atrophy were given diets that contained or lacked either 0.27 percent ursolic acid, or 0.05 percent tomatidine for two months. After 2 months, it was seem that the mice showed a 10 % increased muscle mass; also the muscle quality and strength improved by 30%. These highly noticeable changes suggest that the compounds actually restored muscle mass and strength to young adult levels.

Adam, who also is a member of the Fraternal Order of Eagles Diabetes Research Center at the UI and a staff physician with the Iowa City Veterans Affairs Medical Center, opined that these results are very positive about the potential of ursolic acid and tomatidine for dealing with muscle weakness and atrophy during aging. The researchers also toyed with the idea of using ursolic acid and tomatidine as tools to find a root cause of muscle weakness and atrophy during aging.

When Adam's team studied the molecular effects of ursolic acid and tomatidine in aged skeletal muscle, they found that both compounds turn off a group of genes that are turned on by the transcription factor ATF4. This finding made the scientist to engineer and study a new strain of mice “ the ones that lacked ATF4 in skeletal muscle. It was found that like old muscles that were treated with ursolic acid and tomatidine, old muscles that lacked ATF4 were resistant to the effects of aging.

Adam said that it can be concluded that by reducing ATF4 activity, ursolic acid and tomatidine allow skeletal muscle to recover from effects of aging.

The UI study was done in collaboration with Emmyon, Inc., a UI-based biotechnology company founded by Adams. It is now working to translate ursolic acid and tomatidine into foods, supplements, and pharmaceuticals that can help to fight muscle aging and atrophy.

Looking for a natural way to fight aging? Try this guide.