The Sirt2-Nur77 axis regulates muscle stem cell quiescence and senescence via epigenetic-metabolic synergy - PubMed
3 hours ago
- #muscle stem cells
- #epigenetics
- #aging
- The Sirt2-Nur77 axis regulates muscle stem cell quiescence and senescence through epigenetic-metabolic synergy, with age-related changes observed.
- Nur77 expression decreases with age in multiple organs, while Sirt2 increases in the mouse brain; in aging skeletal muscle, Nur77 is reduced and Sirt2 is elevated, particularly in fast-twitch fibers.
- Sirt2 promotes Nur77 degradation via deacetylation at K310, weakening Myf5 transcriptional activity and altering satellite cell metabolic heterogeneity, affecting muscle homeostasis and regeneration.
- Inhibition of Sirt2 or activation of Nur77 improved muscle function in aged mice, while the K310R mutation led to muscle atrophy and impaired regeneration.
- The Sirt2-P300/Nur77 axis is identified as a potential therapeutic target for skeletal muscle aging and anti-sarcopenia drug development.