Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS One. 2014 Apr 1;9(4):e93074. doi: 10.1371/journal.pone.0093074. eCollection 2014.

Polμ deficiency increases resistance to oxidative damage and delays liver aging.

Author information

  • 1Departamento de Cardiología Regenerativa, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Campus Universidad Autónoma de Madrid, Madrid, Spain.
  • 2Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Campus Universidad Autónoma de Madrid, Madrid, Spain.
  • 3Departamento de Cardiología Regenerativa, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
  • 4Genetic Analysis Group, Promega Corporation, Madison,Wisconsin, United States of America.
  • 5Departamento de Bioquímica y Biología Molecular II, Universidad Complutense, Madrid, Spain.
  • 6Departamento de Epidemiología, Aterotrombosis e Imagen, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
  • 7Institute of Bioengineering, Miguel Hernandez University, Elche (Alicante), Spain.
  • 8Centro de Biología Molecular Severo Ochoa/CSIC, Cantoblanco, Madrid, Spain.
  • 9Institute of Bioengineering, Miguel Hernandez University, Elche (Alicante), Spain; CIBERobn(CB12/03/30038) Instituto de Salud Carlos, Madrid, Spain.
  • 10Bellvitge Biomedical Research Institut (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.

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.

PMID:
24691161
PMCID:
PMC3972199
DOI:
10.1371/journal.pone.0093074
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center