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Kinase inhibitor GW8510 rejuvenates yeast and mice through multiple pathways including SRC, PAKs, JAKs

ABSTRACT: Aging, a risk factor for many diseases, is largely attributable to cell senescence and impaired mitochondrial function. Here, we used connectivity map (CMAP) to predict the anti-aging effects of drugs based on age-related transcriptomic signatures. We found the kinase inhibitor GW8510 can extend lifespan of yeast, and C57BL/6J or ICR mice by 92.18%, 31.9%, and 142.9%, respectively. Mechanistically, GW8510 can ameliorate cellular senescence by enhancing mitochondrial function, decreasing SA-β-gal staining, p21 and SASP marker expression, and rescues age-related histomorphological changes in mouse hippocampus, heart, kidney and liver. In yeast, the action of GW8510 is dependent on STE20, and in human cells, GW8510 acts through various pathways such as SRC, PAKs, and JAKs. Furthermore, inhibiting these genes can delay cellular senescence. This work provides a valuable resource for mechanistic aging studies and suggests strong clinical potential for GW8510.

ORGANISM(S): Homo sapiens

PROVIDER: GSE216516 | GEO | 2023/10/30

REPOSITORIES: GEO

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A benzenesulfonamide GW8510 rejuvenates mice and yeast through interaction with p21-Activated kinases

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