A team of scientists from China has made a breakthrough in understanding how aging affects muscles and found a possible way to slow this process down.
The study, led by Professor Liu Guanghui from the Institute of Zoology at the Chinese Academy of Sciences and Dr. Wang Si from Xuanwu Hospital at Capital Medical University, has revealed that a protein called SIRT5 plays a key role in keeping muscles healthy as we age.
Their research, recently published in Nature Metabolism, explored how SIRT5, sometimes called a “longevity protein,” helps protect muscles from age-related decline. As people get older, their muscles naturally lose mass and strength.
This can lead to serious health problems like difficulty walking, a higher risk of falling, and a greater chance of chronic diseases. Even though this issue affects millions of people, there are currently few treatments that directly address muscle aging.
Muscles are not just important for movement—they’re also key players in how our bodies process energy. So keeping muscles strong isn’t just about staying fit—it’s vital for overall health and independence in older age.
In this study, the scientists used a primate model to study how skeletal muscles change with age. They found several typical signs of muscle aging: smaller muscle fibers, changes in the types of muscle fibers present, increased inflammation, and fewer muscle stem cells (which are needed to repair damaged muscle).
One of the most important discoveries was that levels of the SIRT5 protein were much lower in older muscle tissue. To understand why this mattered, the researchers looked at how SIRT5 interacts with another protein called TBK1, which is known to trigger inflammation in the body.
They found that SIRT5 helps keep TBK1 in check. It does this by removing a chemical marker (called a succinyl group) from TBK1, which stops TBK1 from activating inflammation pathways. Without enough SIRT5, TBK1 becomes more active, leading to more inflammation and faster muscle aging.
Once they understood this, the researchers went a step further. They created a gene therapy treatment using a lentivirus—a type of virus often used in medical research—to deliver extra copies of the SIRT5 gene into the muscles of aged mice.
The results were impressive. After five weeks of treatment, the mice that received the therapy showed stronger physical performance, bigger muscle fibers, lower levels of inflammation, and more youthful gene activity. This suggests that increasing SIRT5 levels could actually reverse some of the effects of muscle aging.
Review and Analysis
This study provides important new insights into why our muscles weaken as we age and what might be done to prevent it. The key finding is that the protein SIRT5 can block harmful inflammation in aging muscles by interacting with another protein, TBK1. Without enough SIRT5, TBK1 activity increases, which speeds up muscle damage and loss.
By restoring SIRT5 levels through gene therapy, the researchers were able to reduce inflammation and improve muscle health in aging mice. These findings are especially exciting because they suggest that one day, we might be able to use similar treatments to help humans stay physically strong and active as they get older.
However, while these results are promising, it’s important to remember that the gene therapy was tested in mice—not people.
More research will be needed to see whether the treatment is safe and effective for humans, especially older adults. Scientists also need to learn more about how SIRT5 behaves in different tissues and what side effects, if any, might come from boosting its activity.
Still, this research is a major step forward in the fight against age-related muscle decline. It not only explains a key reason why muscles age but also opens the door to new ways of treating or even preventing this problem. If future studies confirm these results, SIRT5-based therapies could offer hope for millions of people facing muscle weakness and loss in later life.
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The research findings can be found in Nature Metabolism.
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