Pol? deficiency increases resistance to oxidative damage and delays liver aging.

ABSTRACT: Pol? is an error-prone PolX polymerase that contributes to classical NHEJ DNA repair. Mice lacking Pol? (Pol?(-/-)) show altered hematopoiesis homeostasis and DSB repair and a more pronounced nucleolytic resection of some V(D)J junctions. We previously showed that Pol?(-/-) mice have increased learning capacity at old ages, suggesting delayed brain aging. Here we investigated the effect of Pol?(-/-) deficiency on liver aging. We found that old Pol?(-/-) mice (>20 month) have greater liver regenerative capacity compared with wt animals. Old Pol?(-/-) liver showed reduced genomic instability and increased apoptosis resistance. However, Pol?(-/-) mice did not show an extended life span and other organs (e.g., heart) aged normally. Our results suggest that Pol? deficiency activates transcriptional networks that reduce constitutive apoptosis, leading to enhanced liver repair at old age.

SUBMITTER: Escudero B 

PROVIDER: S-EPMC3972199 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature