Putrescine functions as a metabolic checkpoint in replication stress-induced senescence.

ABSTRACT: Cellular senescence represents a fundamental biological response to replication stress and other genotoxic insults, acting as both a barrier to malignant transformation and a driver of age-related tissue dysfunction. Here, we dissect the metabolic remodeling that accompanies senescence triggered by sustained activation of the replication licensing factor CDC6. Induction of CDC6 in human bronchial epithelial cells provoked a biphasic response characterized by transient hyperproliferation followed by accumulation of senescence-associated β-galactosidase-positive cells. Targeted metabolomics revealed an early increase in intracellular putrescine that was followed by pronounced decline at senescence onset. Functional studies demonstrated that putrescine supplementation attenuated CDC6-induced

SUBMITTER: Vasilogiannakopoulou T 

PROVIDER: S-EPMC12630439 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature