Calorie restriction (CR) reduces age-dependent decline of non-homologous end joining (NHEJ) activity in rat tissues

Even though CR has shown to enhance base excision repair (BER) and nucleotide excision repair (NER) capacities, it has not been reported whether CR can enhance non-homologous end joining (NHEJ) activity. To examine the effect of CR on NHEJ activity, ad libitum (AL)- and calorie restricted (CR)-dieted rats were used. Age-dependent decline of NHEJ activity was apparent in the lung, liver, and kidney and appeared to be slightly decreased in spleen. CR reduced age-dependent decline of NHEJ activity in all tissues, even though the extent of recovery was variable among tissues. Moreover, CR appeared to reduce age-dependent decline of XRCC4 protein level. These results suggest that CR could reduce age-dependent decline of NHEJ activity in various tissues of rats possibly through up-regulation of XRCC4.

[1]  C. Disteche,et al.  Genetic pathway to recurrent chromosome translocations in murine lymphoma involves V(D)J recombinase. , 1999, The Journal of clinical investigation.

[2]  K. S. Rao Dietary calorie restriction, DNA-repair and brain aging , 2003, Molecular and Cellular Biochemistry.

[3]  R. Weindruch Effect of caloric restriction on age-associated cancers , 1992, Experimental Gerontology.

[4]  Jeff A. Stuart,et al.  Mitochondrial and nuclear DNA base excision repair are affected differently by caloric restriction , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[5]  R. Fleischmann,et al.  DNA-PKcs: a T-cell tumour suppressor encoded at the mouse scid locus , 1997, Nature Genetics.

[6]  H. Vogel,et al.  Analysis of ku80-Mutant Mice and Cells with Deficient Levels of p53 , 2000, Molecular and Cellular Biology.

[7]  F. Alt,et al.  The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombination , 1995, Cell.

[8]  Myriam Gorospe,et al.  Calorie Restriction Promotes Mammalian Cell Survival by Inducing the SIRT1 Deacetylase , 2004, Science.

[9]  D. Schild,et al.  Recombinational DNA repair and human disease. , 2002, Mutation research.

[10]  J. Danska,et al.  V(D)J recombination activates a p53-dependent DNA damage checkpoint in scid lymphocyte precursors. , 1996, Genes & development.

[11]  Sheetal Sharma,et al.  Efficiency of nonhomologous DNA end joining varies among somatic tissues, despite similarity in mechanism , 2011, Cellular and Molecular Life Sciences.

[12]  F. Alt,et al.  The Mechanism and Regulation of Chromosomal V(D)J Recombination , 2002, Cell.

[13]  E. Masoro,et al.  Nutritional influences on aging of Fischer 344 rats: I. Physical, metabolic, and longevity characteristics. , 1985, Journal of gerontology.

[14]  A. Richardson,et al.  Nucleotide excision repair of actively transcribed versus nontranscribed DNA in rat hepatocytes: effect of age and dietary restriction. , 1998, Experimental cell research.

[15]  Eric Ravussin,et al.  Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans , 2007, PLoS medicine.

[16]  T. Jacks,et al.  Mutations in the p53 and SCID genes cooperate in tumorigenesis. , 1996, Genes & development.

[17]  F. Alt,et al.  Unrepaired DNA Breaks in p53-Deficient Cells Lead to Oncogenic Gene Amplification Subsequent to Translocations , 2002, Cell.

[18]  Huichen Wang,et al.  Backup pathways of NHEJ are suppressed by DNA‐PK , 2004, Journal of cellular biochemistry.

[19]  D. W. Kim,et al.  Tissue-specific changes of DNA repair protein Ku and mtHSP70 in aging rats and their retardation by caloric restriction , 2003, Mechanisms of Ageing and Development.

[20]  Stephen P. Jackson,et al.  A means to a DNA end: the many roles of Ku , 2004, Nature Reviews Molecular Cell Biology.

[21]  D. Ingram,et al.  Effect of caloric restriction on base-excision repair (BER) in the aging rat brain , 2010, Experimental Gerontology.

[22]  Emilio Clementi,et al.  Calorie Restriction Promotes Mitochondrial Biogenesis by Inducing the Expression of eNOS , 2005, Science.

[23]  Steven P. Gygi,et al.  Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase , 2004, Science.

[24]  P. Klatt,et al.  Impact of telomerase ablation on organismal viability, aging, and tumorigenesis in mice lacking the DNA repair proteins PARP-1, Ku86, or DNA-PKcs , 2004, The Journal of cell biology.

[25]  U. Pendurthi,et al.  Regulation of tissue factor-factor VIIa expression on cell surfaces: A role for tissue factor-factor VIIa endocytes , 2003, Molecular and Cellular Biochemistry.

[26]  H. Vogel,et al.  Deletion of Ku70, Ku80, or Both Causes Early Aging without Substantially Increased Cancer , 2007, Molecular and Cellular Biology.

[27]  H. Vogel,et al.  Deletion of Ku86 causes early onset of senescence in mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[28]  P. Klatt,et al.  Shorter telomeres, accelerated ageing and increased lymphoma in DNA‐PKcs‐deficient mice , 2004, EMBO reports.

[29]  J. Walker,et al.  Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair , 2001, Nature.

[30]  P. Hasty Is NHEJ a tumor suppressor or an aging suppressor? , 2008, Cell cycle.

[31]  K. Schwarz,et al.  DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes. , 1998, Molecular cell.

[32]  D. Reinberg,et al.  Calorie restriction and the exercise of chromatin. , 2009, Genes & development.

[33]  F. Alt,et al.  DNA double strand break repair and chromosomal translocation: Lessons from animal models , 2001, Oncogene.

[34]  D. Roth Restraining the V(D)J recombinase , 2003, Nature Reviews Immunology.

[35]  Delin Chen,et al.  Mammalian SIRT1 Represses Forkhead Transcription Factors , 2004, Cell.

[36]  D. Herr,et al.  Ser18 and 23 phosphorylation is required for p53‐dependent apoptosis and tumor suppression , 2006, The EMBO journal.

[37]  L. Chin,et al.  Impaired nonhomologous end-joining provokes soft tissue sarcomas harboring chromosomal translocations, amplifications, and deletions. , 2001, Molecular cell.

[38]  Barbara Corneo,et al.  Rag mutations reveal robust alternative end joining , 2007, Nature.

[39]  Y. Yamaguchi-Iwai,et al.  Homologous recombination and non‐homologous end‐joining pathways of DNA double‐strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells , 1998, The EMBO journal.

[40]  R. Kanaar,et al.  Rad52 and Ku bind to different DNA structures produced early in double-strand break repair. , 2003, Nucleic acids research.