Scientists discover enzyme that reverses muscle loss due to aging

A groundbreaking study led by researchers from the University of Ottawa’s Faculty of Medicine offers promising insights that could guide the development of future treatments for muscle degeneration. This could benefit those suffering from conditions related to aging, cancer, and muscular dystrophy.

Published in the Journal of Cell Biology, the research highlights the critical role of the enzyme GCN5 in sustaining the production of essential structural proteins in skeletal muscle. These are the muscles responsible for vital functions like breathing, posture, and movement.

The study’s senior author, Dr. Keir Menzies, a molecular biologist at uOttawa, explained that removing GCN5 from muscle tissue severely impairs the muscle’s ability to withstand physical stress. “We found that if you delete GCN5 expression from muscle, it will no longer be able to handle extreme physical stress,” Dr. Menzies said.

The research involved an international collaboration spanning five years, during which the team created muscle-specific GCN5 knockout mice. This approach allowed them to examine what happens when GCN5, an enzyme known to regulate cellular processes like metabolism and inflammation, is absent in muscle tissue. The result was a noticeable decline in muscle health under physical stress.

For this experiment, the researchers subjected the knockout mice to a downhill treadmill run—a form of exercise that can cause micro-tears in muscle fibers, stimulating growth and repair. However, without GCN5, the mice’s muscle fibers weakened dramatically, mimicking the effects of old age. In contrast, wild-type mice, which had normal GCN5 levels, were unaffected by the same exercise.

According to Dr. Menzies, these findings reflect what is seen in advanced aging and diseases like muscular dystrophy, where muscles progressively weaken. This was further supported by human data, which showed a negative correlation between muscle fiber diameter and a multifunctional protein called Yin Yang 1. This protein, which plays a role in various cellular functions, was identified as a target of GCN5 in previous studies.

The most significant takeaway from the study was that GCN5 is responsible for promoting the production of key muscle proteins, particularly dystrophin. Dystrophin is the primary protein that maintains the integrity of muscle cells by acting as an anchor and shock absorber.

Without dystrophin, muscles become highly vulnerable to damage, leading to severe health consequences. Dr. Menzies emphasized, “Our publication shows that if you knock out GCN5, the one major thing we see is a lack of dystrophin, without seeing any real disruption of any other mechanisms.”

Interestingly, the study also confirmed that removing GCN5 doesn’t affect the mitochondria—the part of the cell responsible for producing energy—indicating that GCN5’s role in muscle health is more structural than metabolic.

These findings build upon previous research demonstrating the importance of dystrophin in maintaining muscle health and integrity. Dr. Menzies suggests that understanding GCN5’s function could help in the development of therapies for muscle degeneration in diseases like muscular dystrophy, as well as conditions related to aging.

He explained, “These findings may therefore be useful for the discovery of new therapeutics that regulate GCN5 activity, or its downstream targets, for maintaining healthy muscle during cancer, myopathies, muscular dystrophy, or aging.”

This research brings hope that future treatments targeting GCN5 could provide relief for those dealing with debilitating muscle disorders, offering a pathway to healthier aging and improved quality of life for many individuals.

According to the Cleveland Clinic, the symptoms of muscle atrophy differ depending on the cause of your condition. The most obvious sign of muscle atrophy is reduced muscle mass. Other signs of muscle atrophy may include:

The cause of muscle atrophy depends on the type you have. Disuse (physiologic) atrophy is caused by not using your muscles enough. If you stop using your muscles, your body won’t waste the energy it needs to take care of them. Instead, your body will start to break your muscles down, which causes them to decrease in size and strength.

Disuse atrophy may affect you if you:

Neurogenic atrophy is caused by an injury or disease affecting nerves that connect to your muscles. When these nerves are damaged, they can’t trigger the muscle contractions that are needed to stimulate muscle activity.

When your muscles don’t contract, your body thinks you don’t need them anymore. So your body starts breaking them down, which causes them to decrease in size and strength. Diseases and other conditions that can affect these nerves include:

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