Skip to main content

Advertisement

Log in

Higher DNA repair activity is related with longer replicative life span in mammalian embryonic fibroblast cells

  • Research Article
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

Since the detailed comparison of DNA repair activities among mammalian embryonic fibroblast cells with different replicative life spans has not been investigated, we tested DNA repair activities in embryonic fibroblast cells derived from mammals including human, dog, rat, and mouse. The cell viability after treatment of four DNA damage agents appeared to be decreased in the order of human embryonic fibroblasts (HEFs) > dog embryonic fibroblasts (DEFs) > rat embryonic fibroblasts (REFs) > mouse embryonic fibroblasts (MEFs) although statistical significance was lacking. The amounts of strand breaks and AP (apurinic/apyrimidinic) sites also appear to be decreased in the order of HEFs > DEFs > REFs ≥ MEFs after treatment of DNA damage agents. The DNA repair activities and rates including base excision repair (BER), nucleotide excision repair (NER) and double-strand break repair (DSBR) including non-homologous end-joining (NHEJ) decreased again in the order of HEFs > DEFs > REFs ≥ MEFs. BER and NHEJ activities in 3% O2 also decreased in the order of HEFs > DEFs > REFs > MEFs. This order in DNA repair activity appears to be coincident with that of replicative life span of fibroblasts and that of life span of mammals. These results indicate that higher DNA repair activity is related with longer replicative life span in embryonic fibroblast cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Andreoli C, Leopardi P, Crebelli R (1997) Detection of DNA damage in human lymphocytes by alkaline single cell gel electrophoresis after exposure to benzene or benzene metabolites. Mutat Res 377(1):95–104

    Article  PubMed  CAS  Google Scholar 

  • Andziak B, O’Connor TP, Buffenstein R (2005) Antioxidants do not explain the disparate longevity between mice and the longest-living rodent, the naked mole-rat. Mech Ageing Dev 126(11):1206–1212

    Article  PubMed  CAS  Google Scholar 

  • Athas WF, Hedayati MA, Matanoski GM, Farmer ER, Grossman L (1991) Development and field-test validation of an assay for DNA repair in circulating human lymphocytes. Cancer Res 51(21):5786–5793

    PubMed  CAS  Google Scholar 

  • Barja G (1998) Mitochondrial free radical production and aging in mammals and birds. Ann N Y Acad Sci 854:224–238

    Article  PubMed  CAS  Google Scholar 

  • Barja G, Herrero A (2000) Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals. Faseb J 14(2):312–318

    PubMed  CAS  Google Scholar 

  • Bau DT, Fu YP, Chen ST, Cheng TC, Yu JC, Wu PE, Shen CY (2004) Breast cancer risk and the DNA double-strand break end-joining capacity of nonhomologous end-joining genes are affected by BRCA1. Cancer Res 64(14):5013–5019

    Article  PubMed  CAS  Google Scholar 

  • Borchman D, Yappert MC, Afzal M (2004) Lens lipids and maximum lifespan. Exp Eye Res 79:761–768

    Article  PubMed  CAS  Google Scholar 

  • Boyle J, Kill IR, Parris CN (2005) Heterogeneity of dimer excision in young and senescent human dermal fibroblasts. Aging Cell 4(5):247–255

    Article  PubMed  CAS  Google Scholar 

  • Brown MF, Stuart JA (2007) Correlation of mitochondrial superoxide dismutase and DNA polymerase b in mammalian dermal fibroblasts with species maximal lifespan. Mech Ageing Dev 128:696–705

    Article  PubMed  CAS  Google Scholar 

  • Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME (2004) Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303:2011–2015

    Article  PubMed  CAS  Google Scholar 

  • Christiansen M, Stevnsner T, Bohr VA, Clark BF, Rattan SI (2000) Gene-specific DNA repair of pyrimidine dimers does not decline during cellular aging in vitro. Exp Cell Res 256(1):308–314

    Article  PubMed  CAS  Google Scholar 

  • Cooke MS, Evans MD, Dizdaroglu M, Lunec J (2003) Oxidative DNA damage: mechanisms, mutation, and disease. Faseb J 17(10):1195–1214

    Article  PubMed  CAS  Google Scholar 

  • Cutler RG (1991) Antioxidants and aging. Am J Clin Nutr 53(1 Suppl):373S–379S

    PubMed  CAS  Google Scholar 

  • Foksinski M, Rozalski R, Guz J, Ruszkowska B, Sztukowska P, Piwowarski M, Klungland A, Olinski R (2004) Urinary excretion of DNA repair products correlates with metabolic rates as well as with maximum life spans of different mammalian species. Free Radic Biol Med 37(9):1449–1454

    Article  PubMed  CAS  Google Scholar 

  • Goukassian D, Gad F, Yaar M, Eller MS, Nehal US, Gilchrest BA (2000) Mechanisms and implications of the age-associated decrease in DNA repair capacity. FASEB J 14(10):1325–1334

    Article  PubMed  CAS  Google Scholar 

  • Hamilton ML, Van Remmen H, Drake JA, Yang H, Guo ZM, Kewitt K, Walter CA, Richardson A (2001) Does oxidative damage to DNA increase with age? Proc Natl Acad Sci USA 98(18):10469–10474

    Article  PubMed  CAS  Google Scholar 

  • Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345(6274):458–460

    Article  PubMed  CAS  Google Scholar 

  • Harrigan JA, Wilson DM III, Prasad R, Opresko PL, Beck G, May A, Wilson SH, Bohr VA (2006) The Werner syndrome protein operates in base excision repair and cooperates with DNA polymerase beta. Nucleic Acids Res 34(2):745–754

    Article  PubMed  CAS  Google Scholar 

  • Hart RW, Setlow RB (1974) Correlation between deoxyribonucleic acid excision-repair and life-span in a number of mammalian species. Proc Natl Acad Sci USA 71(6):2169–2173

    Article  PubMed  CAS  Google Scholar 

  • Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25:585–621

    Article  Google Scholar 

  • Imam SZ, Karahalil B, Hogue BA, Souza-Pinto NC, Bohr VA (2006) Mitochondrial and nuclear DNA-repair capacity of various brain regions in mouse is altered in an age-dependent manner. Neurobiol Aging 27(8):1129–1136

    Article  PubMed  CAS  Google Scholar 

  • Kapahi P, Boulton ME, Kirkwood TB (1999) Positive correlation between mammalian life span and cellular resistance to stress. Free Radic Biol Med 26(5–6):495–500

    Article  PubMed  CAS  Google Scholar 

  • Kim HS, Yeo EJ, Park SH, Park JI, Park SC, Shin JY, Kim MJ, Oh SJ, Won MH, Kang TC, Park JB, Kim J, Kim JI, Lee HY, Lee JY (2005) p21WAF/CIP1/SDI1 is upregulated due to increased mRNA stability during hydroxyurea-induced senescence of human fibroblasts. Mech Ageing Dev 126(12):1255–1261

    Article  PubMed  CAS  Google Scholar 

  • Ku HH, Brunk UT, Sohal RS (1993) Relationship between mitochondrial superoxide and hydrogen peroxide production and longevity of mammalian species. Free Radic Biol Med 15(6):621–627

    Article  PubMed  CAS  Google Scholar 

  • Lambert AJ, Boysen HM, Buckingham JA, Yang T, Podlutsky A, Austad SN, Kunz TH, Buffenstein R, Brand MD (2007) Low rates of hydrogen peroxide production by isolated heart mitochondria associate with long maximum lifespan in vertebrate homeotherms. Aging Cell 6(5):607–618

    Article  PubMed  CAS  Google Scholar 

  • Levine RL (2002) Carbonyl modified proteins in cellular regulation, aging, and disease. Free Radic Biol Med 32(9):790–796

    Article  PubMed  CAS  Google Scholar 

  • Lombard DB, Chua KF, Mostoslavsky R, Franco S, Gostissa M, Alt FW (2005) DNA repair, genome stability, and aging. Cell 120(4):497–512

    Article  PubMed  CAS  Google Scholar 

  • Merkle TJ, O’Brien K, Brooks PJ, Tarone RE, Robbins JH (2004) DNA repair in human fibroblasts, as reflected by host-cell reactivation of a transfected UV-irradiated luciferase gene, is not related to donor age. Mutat Res 554:9–17

    Article  PubMed  CAS  Google Scholar 

  • Motta MC, Divecha N, Lemieux M, Kamel C, Chen D, Gu W, Bultsma Y, McBurney M, Guarente L (2004) Mammalian SIRT1 represses forkhead transcription factors. Cell 116:551–563

    Article  PubMed  CAS  Google Scholar 

  • Nakamura J, Swenberg JA (1999) Endogenous apurinic/apyrimidinic sites in genomic DNA of mammalian tissues. Cancer Res 59(11):2522–2526

    PubMed  CAS  Google Scholar 

  • Pamplona R, Portero-Otin M, Ruiz C, Gredilla R, Herrero A, Barja G (2000) Double bond content of phospholipids and lipid peroxidation negatively correlate with maximum longevity in the heart of mammals. Mech Ageing Dev 112(3):169–183

    Article  PubMed  CAS  Google Scholar 

  • Parrinello S, Samper E, Krtolica A, Goldstein J, Melov S, Campisi J (2003) Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol 5(8):741–747

    Article  PubMed  CAS  Google Scholar 

  • Perrault R, Wang H, Wang M, Rosidi B, Iliakis G (2004) Backup pathways of NHEJ are suppressed by DNA-PK. J Cell Biochem 92(4):781–794

    Article  PubMed  CAS  Google Scholar 

  • Rohme D (1981) Evidence for a relationship between longevity of mammalian species and life spans of normal fibroblasts in vitro and erythrocytes in vivo. Proc Natl Acad Sci USA 78(8):5009–5013

    Article  PubMed  CAS  Google Scholar 

  • Ruiz MC, Ayala V, Portero-Otin M, Requena JR, Barja G, Pamplona R (2005) Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals. Mech Ageing Dev 126:1106–1114

    Article  PubMed  CAS  Google Scholar 

  • Sauvaigo S, Caillat S, Odin F, Nkengne A, Bertin C, Oddos T (2010) Effect of aging on DNA excision/synthesis repair capacities of human skin fibroblasts. J Invest Dermatol 130:1739–1741

    Article  PubMed  CAS  Google Scholar 

  • Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175(1):184–191

    Article  PubMed  CAS  Google Scholar 

  • Smogorzewska A, de Lange T (2002) Different telomere damage signaling pathways in human and mouse cells. EMBO J 21(16):4338–4348

    Article  PubMed  CAS  Google Scholar 

  • Stenerlow B, Karlsson KH, Cooper B, Rydberg B (2003) Measurement of prompt DNA double-strand breaks in mammalian cells without including heat-labile sites: results for cells deficient in nonhomologous end joining. Radiat Res 159(4):502–510

    Article  PubMed  CAS  Google Scholar 

  • Takahashi Y, Moriwaki S, Sugiyama Y, Endo Y, Yamazaki K, Mori T, Takigawa M, Inoue S (2005) Decreased gene expression responsible for post-ultraviolet DNA repair synthesis in aging: a possible mechanism of age-related reduction in DNA repair capacity. J Invest Dermatol 124(2):435–442

    Article  PubMed  CAS  Google Scholar 

  • Tsai WB, Chung YM, Takahashi Y, Xu Z, Hu MC (2008) Functional interaction between FOXO3a and ATM regulates DNA damage response. Nat Cell Biol 10(4):460–467

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0029642).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jae-Yong Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Park, SH., Kang, HJ., Kim, HS. et al. Higher DNA repair activity is related with longer replicative life span in mammalian embryonic fibroblast cells. Biogerontology 12, 565–579 (2011). https://doi.org/10.1007/s10522-011-9355-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-011-9355-2

Keywords

Navigation