Polμ deficiency increases resistance to oxidative damage and delays liver aging

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

Polμ deficiency increases resistance to oxidative damage and delays liver aging

Polμ is an error-prone PolX polymerase that contributes to classical NHEJ DNA repair. Mice lacking Polm (Polμ-/-) show altered hematopoiesis homeostasis and DSB repair and a more pronounced nucleolytic resection of some V(D)J junctions. We previously showed that Polμ-/- mice have increased learning capacity at old ages, suggesting delayed brain aging. Here we investigated the effect of Polμ-/- deficiency on liver aging. We found that old Polμ-/- mice (>20 month) have greater liver regenerative capacity compared with wt animals. Old Polμ-/- liver showed reduced genomic instability and increased apoptosis resistance. However, Polμ-/- mice did not show an extended life span and other organs (e.g., heart) aged normally. Our results suggest that Polμ deficiency activates transcriptional networks that reduce constitutive apoptosis, leading to enhanced liver repair at old age. © 2014 Escudero et al.Ministry of Science and Innovation (SAF 2008-02099; PLE2009-0147 and PSE-010000-2009-3), Comunidad Autónoma de Madrid (S2010/BMD-2420), and the European Commission (FP7-HEALTH-2009/CARE-MI. CC is supported by The Spanish Ministry of Economy and Competiveness and the Pro-CNIC FoundationPeer Reviewe

Polμ deficiency increases resistance to oxidative damage and delays liver aging

Polμ is an error-prone PolX polymerase that contributes to classical NHEJ DNA repair. Mice lacking Polμ (Polμ(-/-)) show altered hematopoiesis homeostasis and DSB repair and a more pronounced nucleolytic resection of some V(D)J junctions. We previously showed that Polμ(-/-) mice have increased learning capacity at old ages, suggesting delayed brain aging. Here we investigated the effect of Polμ(-/-) deficiency on liver aging. We found that old Polμ(-/-) mice (>20 month) have greater liver regenerative capacity compared with wt animals. Old Polμ(-/-) liver showed reduced genomic instability and increased apoptosis resistance. However, Polμ(-/-) mice did not show an extended life span and other organs (e.g., heart) aged normally. Our results suggest that Polμ deficiency activates transcriptional networks that reduce constitutive apoptosis, leading to enhanced liver repair at old age.This work was supported by grants to AB from the Ministry of Science and Innovation (SAF 2008-02099; PLE2009-0147 and PSE-010000-2009-3), Comunidad Auto´noma de Madrid (S2010/BMD-2420), and the European Commission (FP7-HEALTH-2009/CARE-MI. CC is supported by The Spanish Ministry of Economy and Competiveness and the Pro-CNIC Foundation.S