Amodiaquine ameliorates stress-induced premature cellular senescence via promoting SIRT1-mediated HR repair.

ABSTRACT: DNA damage is considered to be a potentially unifying driver of ageing, and the stalling of DNA damage repair accelerates the cellular senescence. However, augmenting DNA repair has remained a great challenge due to the intricate repair mechanisms specific for multiple types of lesions. Herein, we miniaturized our modified detecting system for homologous recombination (HR) into a 96-well-based platform and performed a high-throughput chemical screen for FDA-approved drugs. We uncovered that amodiaquine could significantly augment HR repair at the noncytotoxic concentration. Further experiments demonstrated that amodiaquine remarkably suppressed stress-induced premature cellular senescence (SIPS), as evidenced by senescence-associated beta-galactosidase (SA-β-gal) staining or senescence-rel

SUBMITTER: Du J 

PROVIDER: S-EPMC11470136 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature