Table of Contents Author Guidelines Submit a Manuscript
Current Gerontology and Geriatrics Research
Volume 2011 (2011), Article ID 859415, 15 pages
http://dx.doi.org/10.1155/2011/859415
Review Article

Metabolism, Genomics, and DNA Repair in the Mouse Aging Liver

1Centre de Recherche en Cancérologie de l'Université Laval, Hôpital Hôtel-Dieu de Québec, 9 McMahon Street Quebec City, QC, Canada G1R 2J6
2Departmento de Bioquímica, Instituto de Química, Universiade de São Paulo, Avenue Prof. Lineu Prestes, 748, 05508-900 São Paulo, SP, Brazil
3Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA

Received 27 December 2010; Accepted 11 February 2011

Academic Editor: Victoria Cogger

Copyright © 2011 Michel Lebel et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. G. Le Couteur, A. Warren, V. C. Cogger et al., “Old age and the hepatic sinusoid,” Anatomical Record, vol. 291, no. 6, pp. 672–683, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. S. N. Hilmer, V. C. Cogger, R. Fraser, A. J. McLean, D. Sullivan, and D. G. Le Couteur, “Age-related changes in the hepatic sinusoidal endothelium impede lipoprotein transfer in the rat,” Hepatology, vol. 42, no. 6, pp. 1349–1354, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. K. Turnheim, “When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly,” Experimental Gerontology, vol. 38, no. 8, pp. 843–853, 2003. View at Publisher · View at Google Scholar · View at Scopus
  4. R. M. Wright and R. W. Warpula, “Geriatric pharmacology: safer prescribing for the elderly patient,” Journal of the American Podiatric Medical Association, vol. 94, no. 2, pp. 90–97, 2004. View at Google Scholar · View at Scopus
  5. S. X. Cao, J. M. Dhahbi, P. L. Mote, and S. R. Spindler, “Genomic profiling of short- and long-term caloric restriction effects in the liver of aging mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 19, pp. 10630–10635, 2001. View at Publisher · View at Google Scholar · View at Scopus
  6. D. L. Smith Jr., T. R. Nagy, and D. B. Allison, “Calorie restriction: what recent results suggest for the future of ageing research,” European Journal of Clinical Investigation, vol. 40, no. 5, pp. 440–450, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. L. J. Niedernhofer, G. A. Garinis, A. Raams et al., “A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis,” Nature, vol. 444, no. 7122, pp. 1038–1043, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. P. Alexander, “The role of DNA lesions in the processes leading to aging in mice,” Symposia of the Society for Experimental Biology, vol. 21, pp. 29–50, 1967. View at Google Scholar · View at Scopus
  9. J. C. Mirsalis, G. S. Provost, C. D. Matthews et al., “Induction of hepatic mutations in lacI transgenic mice,” Mutagenesis, vol. 8, no. 3, pp. 265–271, 1993. View at Google Scholar · View at Scopus
  10. G. R. Stuart and B. W. Glickman, “Through a glass, darkly: reflections of mutation from lacI transgenic mice,” Genetics, vol. 155, no. 3, pp. 1359–1367, 2000. View at Google Scholar · View at Scopus
  11. H. J. Jorg-Martus, M. E. T. Dolle, J. A. Gossen, M. E. T. I. Boerrigter, and J. Vijg, “Use of transgenic mouse models for studying somatic mutations in aging,” Mutation Research, vol. 338, no. 1–6, pp. 203–213, 1995. View at Publisher · View at Google Scholar · View at Scopus
  12. G. R. Stuart, Y. Oda, J. G. De Boer, and B. W. Glickman, “Mutation frequency and specificity with age in liver, bladder and brain of lacI transgenic mice,” Genetics, vol. 154, no. 3, pp. 1291–1300, 2000. View at Google Scholar · View at Scopus
  13. J. A. Gossen, W. J. F. De Leeuw, C. H. T. Tan et al., “Efficient rescue of integrated shuttle vectors from transgenic mice: a model for studying mutations in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 20, pp. 7971–7975, 1989. View at Google Scholar · View at Scopus
  14. R. R. Swiger, B. Myhr, and J. D. Tucker, “The LacZ transgene in Muta(TM)Mouse maps to chromosome 3,” Mutation Research, vol. 325, no. 4, pp. 145–148, 1994. View at Publisher · View at Google Scholar · View at Scopus
  15. M. E. T. Dolle, H. Giese, C. L. Hopkins, H. J. Martus, J. M. Hausdorff, and J. Vijg, “Rapid accumulation of genome rearrangements in liver but not in brain of old mice,” Nature Genetics, vol. 17, no. 4, pp. 431–434, 1997. View at Google Scholar · View at Scopus
  16. M. E. T. I. Boerrigter, M. E. T. Dolle, H. J. Martus, J. A. Gossen, and J. Vijg, “Plasmid-based transgenic mouse model for studying in vivo mutations,” Nature, vol. 377, no. 6550, pp. 657–659, 1995. View at Google Scholar · View at Scopus
  17. J. Vijg and M. E. T. Dolle, “Large genome rearrangements as a primary cause of aging,” Mechanisms of Ageing and Development, vol. 123, no. 8, pp. 907–915, 2002. View at Publisher · View at Google Scholar · View at Scopus
  18. S. Gupta, “Hepatic polyploidy and liver growth control,” Seminars in Cancer Biology, vol. 10, no. 3, pp. 161–171, 2000. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Celton-Morizur, G. Merlen, D. Couton, and C. Desdouets, “Polyploidy and liver proliferation: central role of insulin signaling,” Cell Cycle, vol. 9, no. 3, pp. 460–466, 2010. View at Google Scholar · View at Scopus
  20. G. R. Gorla, H. Malhi, and S. Gupta, “Polyploidy associated with oxidative injury attenuates proliferative potential of cells,” Journal of Cell Science, vol. 114, no. 16, pp. 2943–2951, 2001. View at Google Scholar · View at Scopus
  21. D. Harman, “Aging: a theory based on free radical and radiation chemistry,” Journal of Gerontology, vol. 11, no. 3, pp. 298–300, 1956. View at Google Scholar · View at Scopus
  22. M. Meydani, R. D. Lipman, S. N. Han et al., “The effect of long-term dietary supplementation with antioxidants,” Annals of the New York Academy of Sciences, vol. 854, pp. 352–360, 1998. View at Publisher · View at Google Scholar · View at Scopus
  23. M. M. Page, E. L. Robb, K. D. Salway, and J. A. Stuart, “Mitochondrial redox metabolism: aging, longevity and dietary effects,” Mechanisms of Ageing and Development, vol. 131, no. 4, pp. 242–252, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. A. Boveris, “Mitochondrial production of superoxide radical and hydrogen peroxide,” Advances in Experimental Medicine and Biology, vol. 78, pp. 67–82, 1977. View at Google Scholar · View at Scopus
  25. A. J. Kowaltowski, N. C. de Souza-Pinto, R. F. Castilho, and A. E. Vercesi, “Mitochondria and reactive oxygen species,” Free Radical Biology and Medicine, vol. 47, no. 4, pp. 333–343, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Dizdaroglu, “Characterization of free radical-induced damage to DNA by the combined use of enzymatic hydrolysis and gas chromatography-mass spectrometry,” Journal of Chromatography, vol. 367, no. 2, pp. 357–366, 1986. View at Google Scholar · View at Scopus
  27. K. C. Cheng, D. S. Cahill, H. Kasai, S. Nishimura, and L. A. Loeb, “8-hydroxyguanine, an abundant form of oxidative DNA damage, causes G → T and A → C substitutions,” Journal of Biological Chemistry, vol. 267, no. 1, pp. 166–172, 1992. View at Google Scholar · View at Scopus
  28. K. A. Hill, A. Halangoda, P. W. Heinmoeller et al., “Tissue-specific time courses of spontaneous mutation frequency and deviations in mutation pattern are observed in middle to late adulthood in big blue mice,” Environmental and Molecular Mutagenesis, vol. 45, no. 5, pp. 442–454, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. M. E. T. Dolle, W. K. Snyder, D. B. Dunson, and J. Vijg, “Mutational fingerprints of aging,” Nucleic Acids Research, vol. 30, no. 2, pp. 545–549, 2002. View at Google Scholar · View at Scopus
  30. Y. Hong, R. B. Cervantes, E. Tichy, J. A. Tischfield, and P. J. Stambrook, “Protecting genomic integrity in somatic cells and embryonic stem cells,” Mutation Research, vol. 614, no. 1-2, pp. 48–55, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. L. Mikkelsen, K. Bialkowski, L. Risom, M. Løhr, S. Loft, and P. Møller, “Aging and defense against generation of 8-oxo-7,8-dihydro-2′-deoxyguanosine in DNA,” Free Radical Biology and Medicine, vol. 47, no. 5, pp. 608–615, 2009. View at Publisher · View at Google Scholar · View at Scopus
  32. R. K. Zahn, G. Zahn-Daimler, S. Ax et al., “DNA damage susceptibility and repair in correlation to calendric age and longevity,” Mechanisms of Ageing and Development, vol. 119, no. 3, pp. 101–112, 2000. View at Publisher · View at Google Scholar · View at Scopus
  33. N. E. López-Diazguerrero, A. Luna-López, M. C. Gutiérrez-Ruiz, A. Zentella, and M. Königsberg, “Susceptibility of DNA to oxidative stressors in young and aging mice,” Life Sciences, vol. 77, no. 22, pp. 2840–2854, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. M. L. Hamilton, H. Van Remmen, J. A. Drake et al., “Does oxidative damage to DNA increase with age?” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 18, pp. 10469–10474, 2001. View at Publisher · View at Google Scholar · View at Scopus
  35. C. S. Fu, S. B. Harris, P. Wilhelmi, and R. L. Walford, “Lack of effect of age and dietary restriction on DNA single-stranded breaks in brain, liver, and kidney of (C3H x C57BL/10)F1 mice,” Journals of Gerontology, vol. 46, no. 2, pp. B78–B80, 1991. View at Google Scholar · View at Scopus
  36. R. M. Anson, S. Sentürker, M. Dizdaroglu, and V. A. Bohr, “Measurement of oxidatively induced base lesions in liver from Wistar rats of different ages,” Free Radical Biology and Medicine, vol. 27, no. 3-4, pp. 456–462, 1999. View at Publisher · View at Google Scholar · View at Scopus
  37. A. Collins, C. Gedik, N. Vaughan et al., “Comparative analysis of baseline 8-oxo-7,8-dihydroguanine in mammalian cell DNA, by different methods in different laboratories: an approach to consensus,” Carcinogenesis, vol. 23, no. 12, pp. 2129–2133, 2002. View at Publisher · View at Google Scholar · View at Scopus
  38. J. Hu, N. C. De Souza-Pinto, K. Haraguchi et al., “Repair of formamidopyrimidines in DNA involves different glycosylases: role of the OGG1, NTH1, and NEIL1 enzymes,” Journal of Biological Chemistry, vol. 280, no. 49, pp. 40544–40551, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. H. J. Helbock, K. B. Beckman, M. K. Shigenaga et al., “DNA oxidation matters: the HPLC-electrochemical detection assay of 8-oxo-deoxyguanosine and 8-oxo-guanine,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 1, pp. 288–293, 1998. View at Google Scholar · View at Scopus
  40. C. W. Greider, “Telomere length regulation,” Annual Review of Biochemistry, vol. 65, pp. 337–365, 1996. View at Google Scholar · View at Scopus
  41. G. M. Martin, “Genetic and environmental modulations of chromosomal stability: their roles in aging and oncogenesis,” Annals of the New York Academy of Sciences, vol. 621, pp. 401–417, 1991. View at Google Scholar · View at Scopus
  42. S. Petersen, G. Saretzki, and T. Von Zglinicki, “Preferential accumulation of single-stranded regions in telomeres of human fibroblasts,” Experimental Cell Research, vol. 239, no. 1, pp. 152–160, 1998. View at Publisher · View at Google Scholar · View at Scopus
  43. Z. Wang, D. B. Rhee, J. Lu et al., “Characterization of oxidative guanine damage and repair in mammalian telomeres,” PLoS Genetics, vol. 6, no. 5, Article ID e1000951, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. P. L. Opresko, J. Fan, S. Danzy, D. M. Wilson, and V. A. Bohr, “Oxidative damage in telomeric DNA disrupts recognition by TRF1 and TRF2,” Nucleic Acids Research, vol. 33, no. 4, pp. 1230–1239, 2005. View at Publisher · View at Google Scholar · View at Scopus
  45. G. Z. Li, M. S. Eller, R. Firoozabadi, and B. A. Gilchrest, “Evidence that exposure of the telomere 3′ overhang sequence induces senescence,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 2, pp. 527–531, 2003. View at Publisher · View at Google Scholar · View at Scopus
  46. E. Sahin, S. Colla, M. Liesa et al., “Telomere dysfunction induces metabolic and mitochondrial compromise,” Nature, vol. 470, no. 7334, pp. 359–365, 2011. View at Publisher · View at Google Scholar
  47. C. Wang, D. Jurk, M. Maddick, G. Nelson, C. Martin-ruiz, and T. Von Zglinicki, “DNA damage response and cellular senescence in tissues of aging mice,” Aging Cell, vol. 8, no. 3, pp. 311–323, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. J. W. Gaubatz and B. H. Tan, “Introduction, distribution, and removal of 7-methylguanine in different liver chromatin fractions of young and old mice,” Mutation Research, vol. 375, no. 1, pp. 25–35, 1997. View at Publisher · View at Google Scholar · View at Scopus
  49. R. K. Zahn, G. Zahn-Daimler, S. Ax, M. Hosokawa, and T. Takeda, “Assessment of DNA-protein crosslinks in the course of aging in two mouse strains by use of a modified alkaline filter elution applied to whole tissue samples,” Mechanisms of Ageing and Development, vol. 108, no. 2, pp. 99–112, 1999. View at Publisher · View at Google Scholar · View at Scopus
  50. M. E. T. I. Boerrigter, J. Y. Wei, and J. Vijg, “Induction and repair of benzo[a]pyrene-DNA adducts in C57BL/6 and BALB/c mice: association with aging and longevity,” Mechanisms of Ageing and Development, vol. 82, no. 1, pp. 31–50, 1995. View at Publisher · View at Google Scholar · View at Scopus
  51. J. E. A. Leakey, H. C. Cunny, J. Bazare et al., “Effects of aging and caloric restriction on hepatic drug metabolizing enzymes in the Fisher 344 rat. I: the cytochrome P-450 dependent monooxygenase system,” Mechanisms of Ageing and Development, vol. 48, no. 2, pp. 145–155, 1989. View at Google Scholar · View at Scopus
  52. D. C. Cabelof, J. J. Raffoul, S. Yanamadala, C. Ganir, Z. Guo, and A. R. Heydari, “Attenuation of DNA polymerase β-dependent base excision repair and increased DMS-induced mutagenicity in aged mice,” Mutation Research, vol. 500, no. 1-2, pp. 135–145, 2002. View at Google Scholar · View at Scopus
  53. R. K. Singhal, R. Prasad, and S. H. Wilson, “DNA polymerase β conducts the gap-filling step in uracil-initiated base excision repair in a bovine testis nuclear extract,” Journal of Biological Chemistry, vol. 270, no. 2, pp. 949–957, 1995. View at Publisher · View at Google Scholar · View at Scopus
  54. H. Nilsen and H. E. Krokan, “Base excision repair in a network of defence and tolerance,” Carcinogenesis, vol. 22, no. 7, pp. 987–998, 2001. View at Google Scholar · View at Scopus
  55. A. JA. Podlutsky, I. I. Dianova, V. N. Podust, V. A. Bohr, and G. L. Dianov, “Human DNA polymerase β initiates DNA synthesis during long-patch repair of reduced AP sites in DNA,” EMBO Journal, vol. 20, no. 6, pp. 1477–1482, 2001. View at Publisher · View at Google Scholar · View at Scopus
  56. A. Klungland and T. Lindahl, “Second pathway for completion of human DNA base excision-repair: reconstitution with purified proteins and requirement for DNase IV (FEN1),” EMBO Journal, vol. 16, no. 11, pp. 3341–3348, 1997. View at Publisher · View at Google Scholar · View at Scopus
  57. B. Pascucci, M. Stucki, Z. O. Jónsson, E. Dogliotti, and U. Hübscher, “Long patch base excision repair with purified human proteins. DNA ligase I as patch size mediator for DNA polymerases δ and ε,” Journal of Biological Chemistry, vol. 274, no. 47, pp. 33696–33702, 1999. View at Publisher · View at Google Scholar · View at Scopus
  58. M. Sukhanova, S. Khodyreva, and O. Lavrik, “Poly(ADP-ribose) polymerase 1 regulates activity of DNA polymerase β in long patch base excision repair,” Mutation Research, vol. 685, no. 1-2, pp. 80–89, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. N. C. De Souza-Pinto, B. A. Hogue, and V. A. Bohr, “DNA repair and aging in mouse liver: 8-oxodG glycosylase activity increase in mitochondrial but not in nuclear extracts,” Free Radical Biology and Medicine, vol. 30, no. 8, pp. 916–923, 2001. View at Publisher · View at Google Scholar · View at Scopus
  60. J. W. Gaubatz and B. H. Tan, “Aging affects the levels of DNA damage in postmitotic cells,” Annals of the New York Academy of Sciences, vol. 719, pp. 97–107, 1994. View at Google Scholar · View at Scopus
  61. G. W. Intano, E. J. Cho, C. A. McMahan, and C. A. Walter, “Age-related base excision repair activity in mouse brain and liver nuclear extracts,” Journals of Gerontology A, vol. 58, no. 3, pp. 205–211, 2003. View at Google Scholar · View at Scopus
  62. G. Xu, M. Herzig, V. Rotrekl, and C. A. Walter, “Base excision repair, aging and health span,” Mechanisms of Ageing and Development, vol. 129, no. 7-8, pp. 366–382, 2008. View at Publisher · View at Google Scholar · View at Scopus
  63. N. C. Souza-Pinto, D. L. Croteau, E. K. Hudson, R. G. Hansford, and V. A. Bohr, “Age-associated increase in 8-oxo-deoxyguanosine glycosylase/AP lyase activity in rat mitochondria,” Nucleic Acids Research, vol. 27, no. 8, pp. 1935–1942, 1999. View at Publisher · View at Google Scholar · View at Scopus
  64. Z. M. Guo, A. Heydari, and A. Richardson, “Nucleotide excision repair of actively transcribed versus nontranscribed DNA in rat hepatocytes: effect of age and dietary restriction,” Experimental Cell Research, vol. 245, no. 1, pp. 228–238, 1998. View at Publisher · View at Google Scholar · View at Scopus
  65. Z. A. Medvedev, “Age changes of chromatin. A review,” Mechanisms of Ageing and Development, vol. 28, no. 2-3, pp. 139–154, 1984. View at Google Scholar · View at Scopus
  66. M. K. Thakur, “Age-related changes in the structure and function of chromatin: a review,” Mechanisms of Ageing and Development, vol. 27, no. 3, pp. 263–286, 1984. View at Publisher · View at Google Scholar · View at Scopus
  67. D. Goukassian, F. Gad, M. Yaar, M. S. Eller, U. S. Nehal, and B. A. Gilchrest, “Mechanisms and implications of the age-associated decrease in DNA repair capacity,” FASEB Journal, vol. 14, no. 10, pp. 1325–1334, 2000. View at Google Scholar · View at Scopus
  68. B. Schumacher, J. H. Hoeijmakers, and G. A. Garinis, “Sealing the gap between nuclear DNA damage and longevity,” Molecular and Cellular Endocrinology, vol. 299, no. 1, pp. 112–117, 2009. View at Publisher · View at Google Scholar · View at Scopus
  69. H. Li, J. R. Mitchell, and P. Hasty, “DNA double-strand breaks: a potential causative factor for mammalian aging?” Mechanisms of Ageing and Development, vol. 129, no. 7-8, pp. 416–424, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. R. Kusumoto, L. Dawut, C. Marchetti et al., “Werner protein cooperates with the XRCC4-DNA ligase IV complex in end-processing,” Biochemistry, vol. 47, no. 28, pp. 7548–7556, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. D. B. Lombard, K. F. Chua, R. Mostoslavsky, S. Franco, M. Gostissa, and F. W. Alt, “DNA repair, genome stability, and aging,” Cell, vol. 120, no. 4, pp. 497–512, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. U. Rass, S. A. Compton, J. Matos et al., “Mechanism of Holliday junction resolution by the human GEN1 protein,” Genes and Development, vol. 24, no. 14, pp. 1559–1569, 2010. View at Publisher · View at Google Scholar
  73. O. A. Sedelnikova, I. Horikawa, D. B. Zimonjic, N. C. Popescu, W. M. Bonner, and J. C. Barrett, “Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks,” Nature Cell Biology, vol. 6, no. 2, pp. 168–170, 2004. View at Publisher · View at Google Scholar · View at Scopus
  74. K. Ren and S. Peña De Ortiz, “Non-homologous DNA end joining in the mature rat brain,” Journal of Neurochemistry, vol. 80, no. 6, pp. 949–959, 2002. View at Publisher · View at Google Scholar · View at Scopus
  75. V. N. Vyjayanti and K. S. Rao, “DNA double strand break repair in brain: reduced NHEJ activity in aging rat neurons,” Neuroscience Letters, vol. 393, no. 1, pp. 18–22, 2006. View at Publisher · View at Google Scholar · View at Scopus
  76. J. H. Um, S. J. Kim, D. W. Kim et al., “Tissue-specific changes of DNA repair protein Ku and mtHSP70 in aging rats and their retardation by caloric restriction,” Mechanisms of Ageing and Development, vol. 124, no. 8-9, pp. 967–975, 2003. View at Publisher · View at Google Scholar · View at Scopus
  77. E. S. Han, S. G. Hilsenbeck, A. Richardson, and J. F. Nelson, “cDNA expression arrays reveal incomplete reversal of age-related changes in gene expression by calorie restriction,” Mechanisms of Ageing and Development, vol. 115, no. 3, pp. 157–174, 2000. View at Publisher · View at Google Scholar · View at Scopus
  78. M. J. McKay, C. Troelstra, P. Van Der Spek et al., “Sequence conservation of the rad21 Schizosaccharomyces pombe DNA double- strand break repair gene in human and mouse,” Genomics, vol. 36, no. 2, pp. 305–315, 1996. View at Publisher · View at Google Scholar · View at Scopus
  79. C. D. Berdanier and H. B. Everts, “Mitochondrial DNA in aging and degenerative disease,” Mutation Research, vol. 475, no. 1-2, pp. 169–184, 2001. View at Publisher · View at Google Scholar · View at Scopus
  80. C. Meissner, “Mutations of mitochondrial DNA—cause or consequence of the ageing process?” Zeitschrift fur Gerontologie und Geriatrie, vol. 40, no. 5, pp. 325–333, 2007. View at Publisher · View at Google Scholar · View at Scopus
  81. U. Lakshmipathy and C. Campbell, “Double strand break rejoining by mammalian mitochondrial extracts,” Nucleic Acids Research, vol. 27, no. 4, pp. 1198–1204, 1999. View at Publisher · View at Google Scholar · View at Scopus
  82. P. A. Mason, E. C. Matheson, A. G. Hall, and R. N. Lightowlers, “Mismatch repair activity in mammalian mitochondria,” Nucleic Acids Research, vol. 31, no. 3, pp. 1052–1058, 2003. View at Publisher · View at Google Scholar · View at Scopus
  83. N. C. de Souza-Pinto, P. A. Mason, K. Hashiguchi et al., “Novel DNA mismatch-repair activity involving YB-1 in human mitochondria,” DNA Repair, vol. 8, no. 6, pp. 704–719, 2009. View at Publisher · View at Google Scholar · View at Scopus
  84. M. Berneburg, Y. Kamenisch, J. Krutmann, and M. Röcken, “'To repair or not to repair—no longer a question': repair of mitochondrial DNA shielding against age and cancer,” Experimental Dermatology, vol. 15, no. 12, pp. 1005–1015, 2006. View at Publisher · View at Google Scholar · View at Scopus
  85. M. D. Aamann, M. M. Sorensen, C. Hvitby et al., “Cockayne syndrome group B protein promotes mitochondrial DNA stability by supporting the DNA repair association with the mitochondrial membrane,” FASEB Journal, vol. 24, no. 7, pp. 2334–2346, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. M. Khaidakov, R. H. Heflich, M. G. Manjanatha, M. B. Myers, and A. Aidoo, “Accumulation of point mutations in mitochondrial DNA of aging mice,” Mutation Research, vol. 526, no. 1-2, pp. 1–7, 2003. View at Publisher · View at Google Scholar · View at Scopus
  87. E. K. Hudson, B. A. Hogue, N. C. Souza-Pinto et al., “Age-associated change in mitochondrial DNA damage,” Free Radical Research, vol. 29, no. 6, pp. 573–579, 1998. View at Google Scholar · View at Scopus
  88. L. Piko, A. J. Hougham, and K. J. Bulpitt, “Studies of sequence heterogeneity of mitochondrial DNA from rat and mouse tissues: evidence for an increased frequency of deletions/additions with aging,” Mechanisms of Ageing and Development, vol. 43, no. 3, pp. 279–293, 1988. View at Google Scholar · View at Scopus
  89. S. M. Tanhauser and P. J. Laipis, “Multiple deletions are detectable in mitochondrial DNA of aging mice,” Journal of Biological Chemistry, vol. 270, no. 42, pp. 24769–24775, 1995. View at Publisher · View at Google Scholar · View at Scopus
  90. B. Szczesny, T. K. Hazra, J. Papaconstantinou, S. Mitra, and I. Boldogh, “Age-dependent deficiency in import of mitochondrial DNA glycosylases required for repair of oxidatively damaged bases,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 19, pp. 10670–10675, 2003. View at Publisher · View at Google Scholar · View at Scopus
  91. A. Trifunovic, A. Wredenberg, M. Falkenberg et al., “Premature ageing in mice expressing defective mitochondrial DNA polymerase,” Nature, vol. 429, no. 6990, pp. 417–423, 2004. View at Publisher · View at Google Scholar · View at Scopus
  92. C. C. Kujoth, A. Hiona, T. D. Pugh et al., “Medicine: mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging,” Science, vol. 309, no. 5733, pp. 481–484, 2005. View at Publisher · View at Google Scholar · View at Scopus
  93. A. Trifunovic, A. Hansson, A. Wredenberg et al., “Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 50, pp. 17993–17998, 2005. View at Publisher · View at Google Scholar · View at Scopus
  94. D. C. Haines, S. Chattopadhyay, and J. M. Ward, “Pathology of aging B6;129 mice,” Toxicologic Pathology, vol. 29, no. 6, pp. 653–661, 2001. View at Publisher · View at Google Scholar · View at Scopus
  95. D. Edgar, I. Shabalina, Y. Camara et al., “Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice,” Cell Metabolism, vol. 10, no. 2, pp. 131–138, 2009. View at Publisher · View at Google Scholar · View at Scopus
  96. H. Gu, J. D. Marth, P. C. Orban, H. Mossmann, and K. Rajewsky, “Deletion of a DNA polymerase β gene segment in T cells using cell type-specific gene targeting,” Science, vol. 265, no. 5168, pp. 103–106, 1994. View at Google Scholar · View at Scopus
  97. D. L. Ludwig, M. A. MacInnes, Y. Takiguchi et al., “A murine AP-endonuclease gene-targeted deficiency with post-implantation embryonic progression and ionizing radiation sensitivity,” Mutation Research, vol. 409, no. 1, pp. 17–29, 1998. View at Publisher · View at Google Scholar · View at Scopus
  98. R. S. Tebbs, M. L. Flannery, J. J. Meneses et al., “Requirement for the Xrcc1 DNA base excision repair gene during early mouse development,” Developmental Biology, vol. 208, no. 2, pp. 513–529, 1999. View at Publisher · View at Google Scholar · View at Scopus
  99. N. Puebla-Osorio, D. B. Lacey, F. W. Alt, and C. Zhu, “Early embryonic lethality due to targeted inactivation of DNA ligase III,” Molecular and Cellular Biology, vol. 26, no. 10, pp. 3935–3941, 2006. View at Publisher · View at Google Scholar · View at Scopus
  100. A. Klungland, I. Rosewell, S. Hollenbach et al., “Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 23, pp. 13300–13305, 1999. View at Publisher · View at Google Scholar · View at Scopus
  101. O. Minowa, T. Arai, M. Hirano et al., “Mmh/Ogg1 gene inactivation results in accumulation of 8-hydroxyguanine in mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 8, pp. 4156–4161, 2000. View at Publisher · View at Google Scholar · View at Scopus
  102. M. Osterod, S. Hollenbach, J. G. Hengstler, D. E. Barnes, T. Lindahl, and B. Epe, “Age-related and tissue-specific accumulation of oxidative DNA base damage in 7,8-dihydro-8-oxoguanine-DNA glycosylase (Ogg1) deficient mice,” Carcinogenesis, vol. 22, no. 9, pp. 1459–1463, 2001. View at Google Scholar · View at Scopus
  103. T. Tsuzuki, A. Egashira, and S. Kura, “Analysis of MTH1 gene function in mice with targeted mutagenesis,” Mutation Research, vol. 477, no. 1-2, pp. 71–78, 2001. View at Publisher · View at Google Scholar · View at Scopus
  104. M. Takao, S. I. Kanno, T. Shiromoto et al., “Novel nuclear and mitochondrial glycosylases revealed by disruption of the mouse Nth1 gene encoding an endonuclease III homolog for repair of thymine glycols,” EMBO Journal, vol. 21, no. 13, pp. 3486–3493, 2002. View at Publisher · View at Google Scholar · View at Scopus
  105. B. Karahalil, N. C. De Souza-Pinto, J. L. Parsons, R. H. Elder, and V. A. Bohr, “Compromised incision of oxidized pyrimidines in liver mitochondria of mice deficient in NTH1 and OGG1 glycosylases,” Journal of Biological Chemistry, vol. 278, no. 36, pp. 33701–33707, 2003. View at Publisher · View at Google Scholar · View at Scopus
  106. A. Shibata, D. Maeda, H. Ogino et al., “Role of Parp-1 in suppressing spontaneous deletion mutation in the liver and brain of mice at adolescence and advanced age,” Mutation Research, vol. 664, no. 1-2, pp. 20–27, 2009. View at Publisher · View at Google Scholar · View at Scopus
  107. V. Vartanian, B. Lowell, I. G. Minko et al., “The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 6, pp. 1864–1869, 2006. View at Publisher · View at Google Scholar · View at Scopus
  108. R. H. Eckel, S. M. Grundy, and P. Z. Zimmet, “The metabolic syndrome,” Lancet, vol. 365, no. 9468, pp. 1415–1428, 2005. View at Publisher · View at Google Scholar · View at Scopus
  109. H. Dou, S. Mitra, and T. K. Hazra, “Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2,” Journal of Biological Chemistry, vol. 278, no. 50, pp. 49679–49684, 2003. View at Publisher · View at Google Scholar · View at Scopus
  110. M. E. T. Dolle, R. A. Busuttil, A. M. Garcia et al., “Increased genomic instability is not a prerequisite for shortened lifespan in DNA repair deficient mice,” Mutation Research, vol. 596, no. 1-2, pp. 22–35, 2006. View at Publisher · View at Google Scholar · View at Scopus
  111. M. Murai, Y. Enokido, N. Inamura et al., “Early postnatal ataxia and abnormal cerebellar development in mice lacking Xeroderma pigmentosum group A and Cockayne syndrome group B DNA repair genes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 23, pp. 13379–13384, 2001. View at Publisher · View at Google Scholar · View at Scopus
  112. J. McWhir, J. Selfridge, D. J. Harrison, S. Squires, and D. W. Melton, “Mice with DNA repair gene (ERCC-1) deficiency have elevated levels of p53, liver nuclear abnormalities and die before weaning,” Nature Genetics, vol. 5, no. 3, pp. 217–224, 1993. View at Publisher · View at Google Scholar
  113. G. Weeda, I. Donker, J. De Wit et al., “Disruption of mouse ERCC1 results in a novel repair syndrome with growth failure, nuclear abnormalities and senescence,” Current Biology, vol. 7, no. 6, pp. 427–439, 1997. View at Google Scholar · View at Scopus
  114. J. Y. Park, M.-O. Cho, S. Leonard et al., “Homeostatic imbalance between apoptosis and cell renewal in the liver of premature aging XpdTTD mice,” PLoS ONE, vol. 3, no. 6, Article ID e2346, 2008. View at Publisher · View at Google Scholar
  115. S. W. P. Wijnhoven, R. B. Beems, M. Roodbergen et al., “Accelerated aging pathology in ad libitum fed Xpd mice is accompanied by features suggestive of caloric restriction,” DNA Repair, vol. 4, no. 11, pp. 1314–1324, 2005. View at Publisher · View at Google Scholar · View at Scopus
  116. E. Nevedomskaya, A. Meissner, S. Goraler et al., “Metabolic profiling of accelerated aging ERCC1 mice,” Journal of Proteome Research, vol. 9, no. 7, pp. 3680–3687, 2010. View at Publisher · View at Google Scholar · View at Scopus
  117. I. van der Pluijm, G. A. Garinis, R. M. Brandt et al., “Impaired genome maintenance suppresses the growth hormone–insulin-like growth factor 1 axis in mice with Cockayne syndrome,” PLoS biology, vol. 5, no. 1, p. e2, 2006. View at Publisher · View at Google Scholar
  118. S. Espejel, M. Martín, P. Klatt, J. Martín-Caballero, J. M. Flores, and M. A. Blasco, “Shorter telomeres, accelerated ageing and increased lymphoma in DNA-PKcs-deficient mice,” EMBO Reports, vol. 5, no. 5, pp. 503–509, 2004. View at Publisher · View at Google Scholar · View at Scopus
  119. H. Vogel, D. S. Lim, G. Karsenty, M. Finegold, and P. Hasty, “Deletion of Ku86 causes early onset of senescence in mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 19, pp. 10770–10775, 1999. View at Publisher · View at Google Scholar · View at Scopus
  120. R. A. Busuttil, D. P. Muñoz, A. M. Garcia et al., “Effect of Ku80 deficiency on mutation frequencies and spectra at a lacZ reporter locus in mouse tissues and cells,” PLoS ONE, vol. 3, no. 10, Article ID e3458, 2008. View at Publisher · View at Google Scholar
  121. N. C. Teoh, Y. Y. Dan, K. Swisshelm et al., “Defective DNA strand break repair causes chromosomal instability and accelerates liver carcinogenesis in mice,” Hepatology, vol. 47, no. 6, pp. 2078–2088, 2008. View at Publisher · View at Google Scholar · View at Scopus
  122. M. L. Rossi, A. K. Ghosh, and V. A. Bohr, “Roles of Werner syndrome protein in protection of genome integrity,” DNA Repair, vol. 9, no. 3, pp. 331–344, 2010. View at Publisher · View at Google Scholar · View at Scopus
  123. M. Lebel and P. Leder, “A deletion within the murine Werner syndrome helicase induces sensitivity to inhibitors of topoisomerase and loss of cellular proliferative capacity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 22, pp. 13097–13102, 1998. View at Publisher · View at Google Scholar · View at Scopus
  124. D. B. Lombard, C. Beard, B. Johnson et al., “Mutations in the WRN gene in mice accelerate mortality in a p53-null background,” Molecular and Cellular Biology, vol. 20, no. 9, pp. 3286–3291, 2000. View at Publisher · View at Google Scholar · View at Scopus
  125. G. Moore, S. Knoblaugh, K. Gollahon, P. Rabinovitch, and W. Ladiges, “Hyperinsulinemia and insulin resistance in Wrn null mice fed a diabetogenic diet,” Mechanisms of Ageing and Development, vol. 129, no. 4, pp. 201–206, 2008. View at Publisher · View at Google Scholar · View at Scopus
  126. S. Chang, A. S. Multani, N. G. Cabrera et al., “Essential role of limiting telomeres in the pathogenesis of Werner syndrome,” Nature Genetics, vol. 36, no. 8, pp. 877–882, 2004. View at Publisher · View at Google Scholar · View at Scopus
  127. X. Du, J. Shen, N. Kugan et al., “Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes,” Molecular and Cellular Biology, vol. 24, no. 19, pp. 8437–8446, 2004. View at Publisher · View at Google Scholar · View at Scopus
  128. L. Massip, C. Garand, R. V. N. Turaga, F. Deschênes, E. Thorin, and M. Lebel, “Increased insulin, triglycerides, reactive oxygen species, and cardiac fibrosis in mice with a mutation in the helicase domain of the Werner syndrome gene homologue,” Experimental Gerontology, vol. 41, no. 2, pp. 157–168, 2006. View at Publisher · View at Google Scholar · View at Scopus
  129. L. Massip, C. Garand, E. R. Paquet et al., “Vitamin C restores healthy aging in a mouse model for Werner syndrome,” FASEB Journal, vol. 24, no. 1, pp. 158–172, 2010. View at Publisher · View at Google Scholar · View at Scopus
  130. A. Labbe, C. Garand, V. C. Cogger et al., “Resveratrol improves insulin resistance hyperglycemia and hepatosteatosis but not hypertriglyceridemia, inflammation, and life span in a mouse model for werner syndrome,” Journals of Gerontology A, vol. 66, no. 3, pp. 264–278, 2011. View at Google Scholar
  131. C. K. Lee, R. G. Klopp, R. Weindruch, and T. A. Prolla, “Gene expression profile of aging and its retardation by caloric restriction,” Science, vol. 285, no. 5432, pp. 1390–1393, 1999. View at Publisher · View at Google Scholar · View at Scopus
  132. A. A. Lachaud, S. Auclair-Vincent, L. Massip, E. Audet-Walsh, M. Lebel, and A. Anderson, “Werner's syndrome helicase participates in transcription of phenobarbital-inducible CYP2B genes in rat and mouse liver,” Biochemical Pharmacology, vol. 79, no. 3, pp. 463–470, 2010. View at Publisher · View at Google Scholar · View at Scopus
  133. F. V. Pallardó, A. Lloret, M. Lebel et al., “Mitochondrial dysfunction in some oxidative stress-related genetic diseases: Ataxia-Telangiectasia, Down Syndrome, Fanconi Anaemia and Werner Syndrome,” Biogerontology, vol. 11, pp. 401–419, 2010. View at Publisher · View at Google Scholar · View at Scopus
  134. J. Sastre, F. V. Pallardó, R. Plá et al., “Aging of the liver: age-associated mitochondrial damage in intact hepatocytes,” Hepatology, vol. 24, no. 5, pp. 1199–1205, 1996. View at Publisher · View at Google Scholar · View at Scopus
  135. C. Musicco, V. Capelli, V. Pesce et al., “Accumulation of overoxidized Peroxiredoxin III in aged rat liver mitochondria,” Biochimica et Biophysica Acta, vol. 1787, no. 7, pp. 890–896, 2009. View at Publisher · View at Google Scholar · View at Scopus
  136. J. A. Baur, K. J. Pearson, N. L. Price et al., “Resveratrol improves health and survival of mice on a high-calorie diet,” Nature, vol. 444, no. 7117, pp. 337–342, 2006. View at Publisher · View at Google Scholar
  137. N. L. Nadon, R. Strong, R. A. Miller et al., “Design of aging intervention studies: the NIA interventions testing program,” Age, vol. 30, no. 4, pp. 187–199, 2008. View at Publisher · View at Google Scholar
  138. R. K. Minor, J. S. Allard, C. M. Younts, T. M. Ward, and R. De Cabo, “Dietary interventions to extend life span and health span based on calorie restriction,” Journals of Gerontology A, vol. 65, no. 7, pp. 695–703, 2010. View at Publisher · View at Google Scholar · View at Scopus