Cordycepin inhibits cell senescence by ameliorating lysosomal dysfunction and inducing autophagy through the AMPK and mTOR-p70S6K pathway
- PMID: 34448542
- PMCID: PMC8487049
- DOI: 10.1002/2211-5463.13263
Cordycepin inhibits cell senescence by ameliorating lysosomal dysfunction and inducing autophagy through the AMPK and mTOR-p70S6K pathway
Abstract
Cell senescence is closely related to autophagy. In this article, we identified a natural nucleoside analogue, cordycepin, that has the ability to significantly improve lysosomal function, enhance the activity of the lysosomal representative protease cathepsin B (CTSB), and promote the expression of the functional protein lysosomal-associated membrane protein 2 (LAMP2) on the lysosomal membrane. Cordycepin then restores the damaged autophagy level of aging cells by activating the classic AMPK and mTOR-p70S6K signaling pathways, thus inhibiting cell senescence in an H2 O2 -induced stress-induced premature senescence (SIPS) cell model. This study provides new theoretical support for the further development of cordycepin and clinical antiaging drugs to inhibit cell senescence and suggests that the regulatory mechanisms of lysosomes in senescent cells should be considered when treating age-related diseases.
Keywords: AMPK signaling pathways; autophagy; cell senescence; cordycepin; lysosomal function; lysosomal protease.
© 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Conflict of interest statement
The authors declare no conflict of interest.
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