Scientists in the United States have made a breakthrough in research to discover the cause of age-related muscle weakness and loss.
It´s thought their work could eventually lead to new treatments for reducing weakness and muscle loss during ageing.
The researchers at the University of Iowa discovered a protein that causes us to lose strength and muscle mass as we grow older. Known as ATF4, this protein is a transcription factor that alters gene expression in skeletal muscle, causing reduction of muscle protein synthesis, strength and mass, the university reported.
The study also identified two natural compounds, one found in apples and one found in green tomatoes, which reduce ATF4 activity in older skeletal muscle.
Previously, the research 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. Subsequently, they set out to test whether the two compounds might be effective in blocking the largest cause of muscle weakness and atrophy: ageing.
In tests with mice, ursolic acid and tomatidine increased muscle mass by 10% and increased muscle quality, or strength, by 30%. According to the researchers, the size of these effects suggests 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 ageing,” said senior study author Christopher Adams. “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 ageing.”
Investigating the molecular effects of ursolic acid and tomatidine in older skeletal muscle, the team found that both compounds turn off a group of genes that are turned on by the transcription factor ATF4. This led them to engineer and study a new strain of mice that lack ATF4 in skeletal muscle. They found that, like old muscles that were treated with ursolic acid and tomatidine, old muscles lacking ATF4 were resistant to the effects of ageing.
“By reducing ATF4 activity, ursolic acid and tomatidine allow skeletal muscle to recover from effects of ageing,” Adams explained.
The study has been published in the Journal of Biological Chemistry.