Mitochondrial Dysfunction in Myoblasts: A TSPO-Dependent Mechanism of Sarcopenia
Peng Zhang1,2, Hongyu Zheng3, Zhao Lin1,2
1Shengli Clinical Medical College, Fujian Medical University, Fuzhou, 350001, China.
Summary
Mitochondrial protein TSPO worsens sarcopenia by disrupting muscle cell growth. Reducing TSPO in aged mice improved muscle mass and function, suggesting TSPO as a therapeutic target for age-related muscle loss.
Area of Science:
- Gerontology
- Molecular Biology
- Muscle Physiology
Background:
- Sarcopenia, the age-related decline in muscle mass and function, is a major health issue in aging populations.
- Mitochondrial dysfunction contributes to sarcopenia, but upstream regulators are not well understood.
Purpose of the Study:
- To identify novel molecular regulators of myogenesis implicated in sarcopenia.
- To investigate the role of the mitochondrial translocator protein (TSPO) in age-related muscle loss.
Main Methods:
- Utilized gain- and loss-of-function studies in C2C12 myoblasts to assess TSPO's impact on myogenesis.
- Investigated the mechanistic link between TSPO, Wnt/β-catenin signaling, and reactive oxygen species (ROS).
- Employed adeno-associated virus serotype 9 (AAV9)-mediated gene knockdown of TSPO in aged mice.
Main Results:
- TSPO was found to be upregulated in aged and sarcopenic muscle, acting as a negative regulator of myogenesis.
- TSPO overexpression impaired mitochondrial homeostasis and myogenic capacity, while TSPO knockdown reversed these effects.
- TSPO suppressed the Wnt/β-catenin pathway, partly via ROS accumulation.
- In vivo TSPO knockdown in aged mice improved mitochondrial integrity, muscle mass, strength, and exercise performance.
Conclusions:
- A novel TSPO-Wnt/β-catenin signaling axis links mitochondrial dysfunction to impaired muscle regeneration in aging.
- Targeting TSPO presents a potential therapeutic strategy for sarcopenia, enhancing mitochondrial function and myogenic signaling.
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