title: Polμ deficiency increases resistance to oxidative damage and delays liver aging.
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.
authors.affiliation: Departamento 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.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Escudero
authors.affiliation: Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Campus Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lucas
authors.affiliation: Departamento de Cardiología Regenerativa, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Albo
authors.affiliation: Departamento de Cardiología Regenerativa, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Suveera
authors.initials: S
authors.lastname: Dhup
authors.affiliation: Genetic Analysis Group, Promega Corporation, Madison,Wisconsin, United States of America.
authors.forename: Jeff W
authors.initials: JW
authors.lastname: Bacher
authors.affiliation: Departamento de Bioquímica y Biología Molecular II, Universidad Complutense, Madrid, Spain.
authors.forename: Aránzazu
authors.initials: A
authors.lastname: Sánchez-Muñoz
authors.affiliation: Departamento de Bioquímica y Biología Molecular II, Universidad Complutense, Madrid, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Fernández
authors.affiliation: Departamento de Epidemiología, Aterotrombosis e Imagen, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Rivera-Torres
authors.affiliation: Departamento 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.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Carmona
authors.affiliation: Institute of Bioengineering, Miguel Hernandez University, Elche (Alicante), Spain.
authors.forename: Encarnación
authors.initials: E
authors.lastname: Fuster
authors.affiliation: Departamento de Cardiología Regenerativa, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Candelas
authors.initials: C
authors.lastname: Carreiro
authors.affiliation: Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Campus Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Bernad
authors.affiliation: Departamento 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.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: González
authors.affiliation: Departamento de Epidemiología, Aterotrombosis e Imagen, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Andrés
authors.affiliation: Centro de Biología Molecular Severo Ochoa/CSIC, Cantoblanco, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Blanco
authors.affiliation: Institute of Bioengineering, Miguel Hernandez University, Elche (Alicante), Spain; CIBERobn(CB12/03/30038) Instituto de Salud Carlos, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Roche
authors.affiliation: Bellvitge Biomedical Research Institut (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Fabregat
authors.affiliation: Departamento 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.
authors.forename: Enrique
authors.initials: E
authors.lastname: Samper
authors.affiliation: Departamento 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.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bernad
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency*; D042822:Genomic Instability; D008099:Liver / Q000473:pathology* / Q000503:physiopathology; D008111:Liver Function Tests; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009206:Myocardium / Q000473:pathology; D018384:Oxidative Stress; D010641:Phenotype; D012854:Sister Chromatid Exchange
chemical_list: C407743:DNA polymerase mu; D004259:DNA-Directed DNA Polymerase