Abstract

Mesenchymal stem cells (MSCs) have been employed for therapeutic applications of various degenerative diseases. However, the major concern is MSC aging during the in vitro cultivation. Thus, the approach to delay MSC aging was examined in this research by focusing on the expression of Sirtuin 1 (SIRT1), a key anti-aging marker. Cordycepin, a bioactive compound derived from Cordyceps militaris, was used to up-regulate SIRT1 and maintain stemness of MSCs. Upon treatment with cordycepin, MSCs were investigated for cell viability, doubling time, key gene/protein expression, galactosidase-associated senescence assay, relative telomere length, and telomerase expression. Cordycepin significantly increased the expression of SIRT1 in MSCs by activating the adenosine monophosphate activated protein kinase (AMPK)-SIRT1 signalling pathway. Moreover, cordycepin maintained the stemness of MSCs by deacetylating SRY-box transcription factor 2 (SOX2) via SIRT1, and cordycepin delayed cellular senescence and aging of MSCs by enhancing autophagy, inhibiting the activity of senescence-associated-galactosidase, maintaining proliferation rate, and increasing telomere activity. Cordycepin could be used to increase SIRT1 expression in MSCs for anti-aging applications.

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