As we grow older, we lose strength and muscle mass. However,
the cause of age-related muscle weakness and atrophy has remained a mystery.
Scientists at the University of Iowa have 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, causing reduction of muscle protein synthesis, strength, and
mass. The UI 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 Sept. 3 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," says Christopher
Adams, MD, PhD, UI professor of internal 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, Adams' team 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 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 increased
muscle mass by 10 percent, and more importantly, increased muscle quality, or
strength, by 30 percent. The sizes of these 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."
Adams' team investigated 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 led them 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.
"By reducing ATF4 activity, ursolic acid and tomatidine
allow skeletal muscle to recover from effects of aging," says Adams, 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.
The UI study was done in collaboration with Emmyon, Inc., a
UI-based biotechnology company founded by Adams, that is now 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.
Story Source:
The above post is reprinted from materials provided by
University of Iowa. The original item was written by Jennifer Brown. Note:
Materials may be edited for content and length.
