Tomatidine, one of the two compounds that inhibit ATF4, can be found naturally occurring in green tomatoes.
The study, published in the Journal of Biological Chemistry, offers the first example of a protein associated with age-related muscle wasting, and could lead toward new forms of treatment.
"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.
Despite the fact that aging can reduce muscle mass and strength is common knowledge, the mechanisms behind this decline have remained unknown.
However, from this new study, the research team concludes that the protein ATF4 is an essential mediator of muscle aging. ATF4 is a transcription factor that influences the expression of certain genes in skeletal muscle, in turn, reducing the strength, mass and synthesis of muscle protein.
Previously, Dr. Adams and colleagues identified two natural compounds that prevent muscle wasting caused by inactivity and starvation. These compounds were ursolic acid, found in apple peel, and tomatidine, found in green tomatoes.
These findings prompted the team to investigate whether the compounds were also capable of preventing muscle wasting caused by aging, using elderly mice with age-related muscle weakness and atrophy.
Ursolic acid, tomatidine have potential for reducing age-related muscle weakness
For the study, the mice were given diets that either contained or lacked specific amounts of these compounds - 0.27% ursolic acid or 0.05% tomatidine.
The mice received these diets for 2 months, after which the researchers evaluated the condition of the mice's muscles.
For the mice whose diets included either of the two compounds, muscle mass increased by around 10% and muscle strength increased by around 30%, restoring them to levels similar to those observed in young adult mice.
Dr. Adams explains what this discovery meant:
"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."
Compounds work by reducing ATF4 activity
Investigating further, the team examined how the compounds worked on a molecular level in aged skeletal muscle. Both ursolic acid and tomatidine deactivated a group of genes that are usually activated by the protein ATF4.
The team then engineered mice without ATF4 in their skeletal muscle. They discovered that the 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 states.
The researchers conclude that the two compounds could potentially be used in nutritional products for preserving strength and muscle mass during aging. A biotechnology company that collaborated with the team on the study - Emmyon, Inc. - is now looking at the possibility of incorporating ursolic acid and tomatidine into foods, supplements and drugs.
"If ursolic acid- and tomatidine-based approaches are found to be safe and effective in humans, they could possibly be used alone, together, or in combination with physical therapy and other nutritional and pharmaceutical approaches," the study authors conclude.
Although aging is the largest cause of muscle weakness and atrophy, it has been shown to have some health benefits. Previously, Medical News Today reported on a study finding that blood vessels adapt during the aging process to reduce damage from oxidative stress.