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  3. Muscle-specific Pgc-1α Modulates Mitochondrial Oxidative Stress In Aged Sarcopenia Through Regulating Nrf2.
  1. Home
  3. Muscle-specific Pgc-1α Modulates Mitochondrial Oxidative Stress In Aged Sarcopenia Through Regulating Nrf2.

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Muscle-specific PGC-1α modulates mitochondrial oxidative stress in aged sarcopenia through regulating Nrf2.

Lei Song1, Jianfeng Xue2, Lingfen Xu3

  • 1Geriatric Medicine Department, Yantai Yuhuangding Hospital, Yantai 264000, China.

Experimental Gerontology
|May 27, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) plays a key role in mitigating age-related muscle loss. This study shows PGC-1α regulates mitochondrial oxidative stress by modulating nuclear factor erythroid 2-related factor 2 (Nrf2).

Keywords:
7β-hydroxycholesterol (7β-OHC)C2C12 cellsCD38PGC-1α conditional knockout (CKO) micePGC-1α siRNA

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Area of Science:

  • Mitochondrial biology
  • Skeletal muscle physiology
  • Aging research

Background:

  • Aged sarcopenia involves skeletal muscle mass and strength decline, with mitochondrial dysfunction as a key factor.
  • Investigating the role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in mitochondrial reactive oxygen species (ROS) and nuclear factor erythroid 2-related factor 2 (Nrf2) in aged skeletal muscles is crucial.

Purpose of the Study:

  • To analyze the effects of PGC-1α on mitochondrial ROS and Nrf2 in aged skeletal muscles.
  • To elucidate the regulatory relationship between PGC-1α and Nrf2 in the context of sarcopenia.

Main Methods:

  • C2C12 myoblasts were treated with 7β-hydroxycholesterol (7β-OHC) to induce oxidative stress and PGC-1α modulation.
  • PGC-1α expression was altered using siRNA or overexpression plasmids to assess impacts on ROS and Nrf2.
  • Studies in wild-type and PGC-1α conditional knockout mice examined PGC-1α's role in sarcopenia, Nrf2, and CD38 expression, with diethylmaleate used as an Nrf2 activator.

    • Main Results:

    • PGC-1α and Nrf2 expression decreased with 7β-OHC treatment or PGC-1α knockdown, while PGC-1α overexpression reduced ROS and increased Nrf2.
    • Diethylmaleate treatment lowered ROS in treated cells and PGC-1α-deficient mice.
    • Muscle-specific PGC-1α deficiency exacerbated sarcopenia, reduced Nrf2, and increased CD38 in aged mice; diethylmaleate improved muscle function and reduced CD38.

    Conclusions:

    • PGC-1α plays a critical role in mitigating mitochondrial oxidative stress in aged sarcopenia.
    • PGC-1α modulates mitochondrial oxidative stress by regulating Nrf2 expression and activity.