A collaborative study led by Prof. Liu Guanghui from the Institute of Zoology, Chinese Academy of Sciences, and Dr. Wang Si from Xuanwu Hospital, Capital Medical University, has uncovered a novel molecular mechanism that may slow down skeletal muscle aging. Published in Nature Metabolism, the research highlights the role of the “longevity protein” SIRT5 in combating muscle decline and presents a potential gene therapy strategy to counteract this process.
The Challenge of Skeletal Muscle Aging
Skeletal muscle plays a crucial role in physical function and energy metabolism. However, aging leads to a gradual loss of muscle mass and strength, increasing the risk of falls, fractures, and chronic diseases. Despite its profound impact on health, effective treatments to prevent muscle aging remain scarce. This study provides new insights into how SIRT5 modulates inflammatory pathways through its interaction with protein kinase TBK1. This interaction offers a promising therapeutic approach.
SIRT5 and Its Role in Muscle Aging
Using a primate model of skeletal muscle aging, researchers identified key aging-related changes such as muscle fiber shrinkage, fiber type shifts, heightened inflammation, and reduced muscle stem cell populations. They found that SIRT5 levels decrease with age, which significantly contributes to muscle deterioration. Further genetic and biochemical analyses revealed that SIRT5 desuccinylates TBK1, suppressing pro-inflammatory signaling pathways and effectively slowing muscle aging.
Gene Therapy Approach Shows Promising Results
To explore potential interventions, the researchers designed a gene therapy strategy using a lentiviral vector to overexpress SIRT5 in aged mice. After five weeks of treatment, the mice displayed notable improvements in:
- Physical performance
- Muscle fiber size
- Inflammation reduction
- Gene expression profiles associated with rejuvenation
As reported by medicalxpress, these findings suggest that SIRT5 overexpression could serve as an effective therapeutic strategy to reverse muscle aging and prevent age-related muscle disorders.
A Step Toward Future Therapies
This study reveals the molecular mechanisms driving skeletal muscle aging. It also identifies SIRT5 as a promising therapeutic target. Researchers may develop future treatments using SIRT5-based interventions. These treatments could enhance muscle health and extend functional longevity.