Reversine ameliorates hallmarks of cellular senescence in human skeletal myoblasts via reactivation of autophagy

Abstract

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.

Neuropathological stage‐dependent proteome mapping of the olfactory tract in Alzheimer's disease: From early olfactory‐related omics signatures to computational repurposing of drug candidates

“…However, their precise role during AD progression is unknown. Reversine has been proposed as a therapeutic option against cellular senescence [ 58 ]. This compound increases the differentiation potential of progenitor cells toward the neuroectodermal lineage [ 59 ].…”

Neuropathological stage-dependent proteome mapping of the olfactory tract in Alzheime’s disease: From early olfactory-related omics signatures to computational repurposing of drug candidates

“…This compound increases differentiation potential of progenitor cells toward the neuroectodermal lineage (56). Interestingly, it has been demonstrated that Reversine is able to reactivate insulin pathway, autophagy, glucose uptake and restore glycolytic-Krebs cycle connectivity, rewiring mitochondrial functionality in senescent cells (55). All these processes are considered hallmarks of a neurodegenerative process (57) suggesting Reversine as a potential therapeutic component in AD.…”

Generation of Mature <em>Toxoplasma gondii</em> Bradyzoites in Human Immortalized Myogenic KD3 Cells

“…This problem may be addressed by improving host cell attachment to the culture vessel using various methods ( Madden et al, 2015 ; Bettadapur et al, 2016 ; Denes et al, 2019 ; Martins et al, 2022 ). Finally, cellular senescence may also pose a limit on the maximal passages of KD3 cells and may be ameliorated by reversine treatment ( Rajabian et al, 2023 ). Mild heat stress from temperature fluctuations of cell culture incubators may also induce differentiation and needs to be avoided ( Yamaguchi et al, 2010 ).…”