Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aging / pathology*
-
Animals
-
DNA-Directed DNA Polymerase / deficiency*
-
Genomic Instability
-
Liver / pathology*
-
Liver / physiopathology
-
Liver Function Tests
-
Mice, Inbred BALB C
-
Mice, Inbred C57BL
-
Models, Biological
-
Myocardium / pathology
-
Oxidative Stress*
-
Phenotype
-
Sister Chromatid Exchange
Substances
-
DNA polymerase mu
-
DNA-Directed DNA Polymerase
Grants and funding
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 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 Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.