Scientists Find Clue to Preventing Age-Related Muscle Loss

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Scientists may have found a way to rejuvenate key cells that help rebuild muscle in the body and thus preserve muscle into old age, they report in a new mouse study.

It is "really exciting stuff," Matthew Krause , a muscle physiologist at the University of Windsor in Ontario, said of the results. It could have clinical applications down the road if shown to work in humans, as well, added Krause, who was not involved in the research.

The body loses muscle with age and with chronic conditions that compromise people's mobility. To find a potential treatment for this muscle atrophy, the scientists behind the new study looked to "satellite cells." These stem cells are located around skeletal muscle fibers and play an important role in muscle regeneration.

Muscles incur microscopic damage with use , and this damage calls satellite cells into action. They proliferate to rebuild muscle fibers, by either merging into the torn muscle cells or forming new muscle cells. With age, satellite cells activate less efficiently and muscles become weak. But the new study, published July 24 in the journal Scientific Reports , suggests that it may be possible to rescue satellite cells from dormancy.

When muscles tear during exercise, a protein called hepatocyte growth factor (HGF) gets released. This is the signal that binds to receptors on satellite cells and activates them. Previously, studies from the same team showed that HGF works less well in old lab mice because its structure is chemically altered by a compound called peroxynitrite, and this makes it harder for HGF to plug into its receptor on satellite cells. This chemical alteration is known as nitration.

Peroxynitrite is produced through the reaction of unstable nitrogen and oxygen molecules, called radicals , said study co-author Ryuichi Tatsumi , a muscle physiologist at Kyushu University in Japan. These radicals are produced during normal metabolism, but their levels increase with age, he explained.

As a result, satellite cells cannot be activated efficiently to trigger muscle growth, even if the amount of HGF itself does not decline. Tatsumi and colleagues showed this in a previous study in rats .

Regular physical activity can help older adults preserve muscle, but even so, muscular tissue tends to weaken with age. (Image credit: Maskot via Getty Images) In the new study, the scientists tested two compounds to see if they could counter this effect in lab mice. They used an experimental setup in which mice couldn't use their muscles as normal, so they weakened; such muscle disuse is known to increase HGF nitration around muscle cells.

Both of the tested compounds are known to protect proteins from damage caused by highly reactive chemicals by intercepting the reaction before it can take place. In experiments, the team treated HGF with each compound before exposing it to peroxynitrite. They found that, compared with untreated HGF, HGF treated with either compound showed substantially lower levels of nitration. This preserved its ability to activate satellite cells grown in lab dishes.

At high concentrations, one of the compounds — lipoic acid trisulfide (LASSS) — not only prevented nitration but also markedly increased HGF's ability to plug into its receptor. That suggests LASSS may chemically modify HGF in a way that could boost its effects.

To see if these observations carried over to living animals, the researchers gave lab mice LASSS in their drinking water. Although these were young mice, they were prevented from bearing weight on their hind limbs for five days, so they experienced short-term muscle disuse. Compared with untreated animals, the mice given LASSS had substantially lower HGF nitration around their muscle cells.

It's "pretty remarkable" that providing LASSS by mouth was sufficient to produce this effect, Krause said. He noted, however, that the researchers did not measure muscle atrophy or try administering LASSS to old mice to see the effects on the muscle. Longer experiments would be needed to observe those changes, he told Live Science.

The compound could also be tested in other forms of muscle wasting, Krause suggested. For example, severe chronic diseases like cancer can cause cachexia , a wasting syndrome marked by dramatic weight and muscle loss.

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In general, protein nitration has been linked to several age-related disorders, including Alzheimer's disease, in which nitrated proteins accumulate in the brain . Understanding how to protect proteins from this kind of chemical damage could have implications beyond muscle biology, Tatsumi said.

However, further studies are still needed to assess the effectiveness and safety of LASSS in older animals. Experiments involving aging animals are expensive and can take a lot of time, Tatsumi said, but he is optimistic that this understanding will help address a range of age-related disorders with this same underlying biology.

"That is our big wish," he told Live Science. "I think, in the near future, we can do that."