Reversine ameliorates hallmarks of cellular senescence in human skeletal myoblasts via reactivation of autophagy.
Nika RajabianDebanik ChoudhuryIzuagie IkhapohShilpashree SahaAishwarya S KalyankarPihu MehrotraAref ShahiniKendall BreedStelios T AndreadisPublished in: Aging cell (2023)
Cellular senescence leads to the depletion of myogenic progenitors and decreased regenerative capacity. We show that the small molecule 2,6-disubstituted purine, reversine, can improve some well-known hallmarks of cellular aging in senescent myoblast cells. Reversine reactivated autophagy and insulin signaling pathway via upregulation of Adenosine Monophosphate-activated protein kinase (AMPK) and Akt2, restoring insulin sensitivity and glucose uptake in senescent cells. Reversine also restored the loss of connectivity of glycolysis to the TCA cycle, thus restoring dysfunctional mitochondria and the impaired myogenic differentiation potential of senescent myoblasts. Altogether, our data suggest that cellular senescence can be reversed by treatment with a single small molecule without employing genetic reprogramming technologies.
Keyphrases
- signaling pathway
- induced apoptosis
- small molecule
- endothelial cells
- endoplasmic reticulum stress
- cell cycle arrest
- cell death
- protein kinase
- pi k akt
- skeletal muscle
- dna damage
- oxidative stress
- epithelial mesenchymal transition
- stem cells
- cell proliferation
- protein protein
- type diabetes
- stress induced
- gene expression
- mesenchymal stem cells
- metabolic syndrome
- resting state
- cell therapy
- electronic health record
- white matter
- adipose tissue
- reactive oxygen species
- risk assessment
- glycemic control
- smoking cessation