Aging Clinical and Experimental Research

, Volume 11, Issue 5, pp 294–300 | Cite as

8-oxo-deoxyguanosine levels in heart and brain mitochondrial and nuclear DNA of two mammals and three birds in relation to their different rates of aging

  • A. Herrero
  • G. Barja
Original Article


Previous studies found that the rate of mitochondrial oxygen radical generation is lower in long-lived birds than in short-lived mammals. In the present study, the oxidative DNA damage marker 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in heart and brain mitochondrial (mtDNA) and nuclear DNA (nDNA) was compared between mammals and birds of approximately similar body size and metabolic rates; rats (maximum life span, MLSP=4 years) vs pigeons (MLSP=35 years), and mice (MLSP=3.5 years) vs parakeets (MLSP=21 years) or canaries (MLSP=24 years). Lower steady-state 8-oxodG values were observed in all cases in the heart mtDNA in birds than in mammals. 8-oxodG levels were also lower in brain mtDNA in pigeons than in rats, in brain nDNA in canaries than in mice, and in heart nDNA in parakeets compared with mice. The rest of the comparisons did not show significant differences between species. These results taken together indicate that oxidative damage to DNA tends to be lower in birds (highly long-lived species) than in short-lived mammals, specially in the case of mtDNA. This is consistent with the low rate of mitochondrial oxygen radical generation observed in all long-lived species investigated up to date, birds or mammals, including the bird species studied here. The results also show that 8-oxodG steady-state levels are much higher in mtDNA than in nDNA in all the tissues (heart and brain) and species (birds and mammals) studied.

Aging free radicals longevity mitochondrial DNA 8-hydroxy-deoxyguanosine oxidative damage 


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  1. 1.
    Sohal R.S., Weindruch R.: Oxidative stress, caloric restriction, and aging. Science 273: 59–63, 1996.Google Scholar
  2. 2.
    Harman D.: The biological clock: the mitochondria? J. Am. Geriatr. Soc. 20: 145–147, 1972.PubMedGoogle Scholar
  3. 3.
    Barja G.: Mitochondrial free radical production and aging in mammals and birds. Ann. N.Y. Acad. Sci. 854: 224–238, 1998.PubMedCrossRefGoogle Scholar
  4. 4.
    Barja G.: Mitochondrial free radical generation: sites of production in states 4 and 3, organ specificity and relationship with aging rate. J. Bioenerg. Biomembr. 31: 347–366, 1999.PubMedCrossRefGoogle Scholar
  5. 5.
    Barja G., Herrero A.: Localization at Complex I and mechanism of the higher free radical production of brain non-synaptic mitochondria in the short-lived rat than in the longevous pigeon. J. Bioenerg. Biomembr. 30: 235–243, 1998.PubMedCrossRefGoogle Scholar
  6. 6.
    Pamplona R., Portero-Otín M., Riba D., Ledo F., Gredilla R., Herrero A., Barja A.: Heart fatty acid unsaturation and lipid peroxidation, and aging rate, are lower in the canary and the parakeet than in the mouse. Aging Clin. Exp. Res. 11: 44–49, 1999.Google Scholar
  7. 7.
    Altman P., Dittmer P.: Life spans: animals. In: Biology Data Book. Fed. Am. Soc. Exp. Biol., Bethesda, 1972, pp. 229–235.Google Scholar
  8. 8.
    Flower S.S.: Further notes on the duration of life in animals — IV Birds. Proc. Zool. Soc. London, Ser. A: 195–235, 1938.Google Scholar
  9. 9.
    Herrero A., Barja G.: Sites and mechanisms responsible for the low rate of free radical production of heart mitochondria in the long-lived pigeon. Mech. Ageing Dev. 98: 95–111, 1997.PubMedCrossRefGoogle Scholar
  10. 10.
    Ku H.H., Sohal R.S.: Comparison of mitochondrial pro-oxidant and antioxidant defenses between rat and pigeon: possible basis of variation in longevity and metabolic potential. Mech. Ageing Dev. 72: 67–76, 1993.PubMedCrossRefGoogle Scholar
  11. 11.
    Herrero A., Barja G.: H2O2 production of heart mitochondria and aging rate are slower in canaries and parakeets than in mice: sites of free radical generation and mechanisms involved. Mech. Ageing Dev. 103: 133–146, 1998.PubMedCrossRefGoogle Scholar
  12. 12.
    Sohal R.S., Agarwal S., Candas M., Forster M.J., Lal H.: Effect of age on DNA oxidative damage in different tissues of C57BL/6 mice. Mech. Ageing Dev. 76: 215–224, 1994.PubMedCrossRefGoogle Scholar
  13. 13.
    Richter C., Park J.W., Ames B.N.: Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc. Natl. Acad. Sci. USA 85: 6465–6467, 1988.Google Scholar
  14. 14.
    Chung M.H., Kasai H., Nishimura S., Yu B.P.: Protection of DNA damage by dietary restriction. Free Radic. Biol. Med. 12: 523–525, 1992.PubMedCrossRefGoogle Scholar
  15. 15.
    Mecocci P., MacGarvey U., Kaufman A.E., Koontz D., Shoffner J.M., Wallace D.C., Beal F.: Oxidative damage to mitochondrial DNA shows age-dependent increases in human brain. Ann. Neurol. 34: 609–616, 1993.PubMedCrossRefGoogle Scholar
  16. 16.
    Loft S., Poulsen H.E.: Markers of oxidative damage to DNA: antioxidants and molecular damage. Methods Enzymol. 300: 166–184, 1999.PubMedGoogle Scholar
  17. 17.
    Cadenas S., Barja G., Poulsen H.E., Loft S.: Oxidative DNA damage estimated by oxo8dG in the liver of guinea-pigs supplemented with graded dietary doses of ascorbic acid and α-tocopherol. Carcinogenesis 18: 2373–2377, 1997.PubMedCrossRefGoogle Scholar
  18. 18.
    Latorre A., Moya A., Ayala A.: Evolution of mitochondrial DNA in Drosophila Suboscura. Proc. Natl. Acad. Sci. USA 83: 8649–8653, 1986.PubMedCrossRefGoogle Scholar
  19. 19.
    Asunción J.G., Millan A., Pla R., Bruseghini L., Esteras A., Pallardo F.V., Sastre J., Viña J.: Mitochondrial glutathione oxidation correlates with age-associated oxidative damage to mitochondrial DNA. FASEB J. 10: 333–338, 1996.PubMedGoogle Scholar
  20. 20.
    Ozawa T.: Mitochondrial DNA mutations and age. Ann. N.Y. Acad. Sci. 854: 128–154, 1998.PubMedCrossRefGoogle Scholar
  21. 21.
    Kovalenko S.A., Kospidas G., Kelso J., Rosenfeldt F., Linnane A.W.: Tissue-specific distribution of multiple mitochondrial DNA rearrangements during human aging. Ann. N.Y. Acad. Sci. 854: 171–181, 1998.PubMedCrossRefGoogle Scholar
  22. 22.
    Lightowlers R.N., Jacobs H.T., Kajander O.A.: Mitochondrial DNA — all thing’s bad? Trends Genet. 15: 91–93, 1999.PubMedCrossRefGoogle Scholar
  23. 23.
    Yoneda M., Chomyn A., Martinuzzi A., Horko O., Attardi G.: Marked replicative advantage of human mtDNA carrying a point mutation that causes the MELAS encephalomyopathy. Proc. Natl. Acad. Sci. USA 89: 11164–11168, 1992.PubMedCrossRefGoogle Scholar
  24. 24.
    de Grey A.D.N.J.: A mechanism proposed to explain the rise in oxidative stress during aging. J. Anti-aging Med. 1: 53–65, 1998.CrossRefGoogle Scholar
  25. 25.
    Brierley E.J., Johnson M.A., Lightowlers R.N., James O.F.W., Turnbull D.M.: Role of mitochondrial DNA mutations in human aging: implications from the central nervous system and muscle. Ann. Neurol. 43: 217–223, 1998.PubMedCrossRefGoogle Scholar
  26. 26.
    Shibutani S., Takeshita M., Grollman A.P.: Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxo-dG. Nature 349: 431–434, 1991.PubMedCrossRefGoogle Scholar
  27. 27.
    Cheng K.C., Cahill D.S., Kasai H., Nishimura S., Loeb L.A.: 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G-T and A-C substitutions. J. Biol. Chem. 267: 166–172, 1992.PubMedGoogle Scholar
  28. 28.
    Ku H.H., Brunk U.T., Sohal R.S.: Relationship between mitochondrial superoxide and hydrogen peroxide production and longevity of mammalian species. Free Radic. Biol. Med. 15: 621–627, 1993.PubMedCrossRefGoogle Scholar
  29. 29.
    Ames B.N.: Endogenous oxidative DNA damage, aging, and cancer. Free Radic. Res. Commun. 7: 121–128, 1989.PubMedCrossRefGoogle Scholar
  30. 30.
    Adelman R., Saul R.L., Ames B.N.: Oxidative damage to DNA: Relation to species metabolic rate and life span. Proc. Natl. Acad. Sci. USA 85: 2706–2708, 1988.PubMedCrossRefGoogle Scholar
  31. 31.
    Ogburn C.E., Austad S.N., Holmes D.J., Kiklevich J.V., Gollahon K., Rabinovitch P.S., Martin G.M.: Cultured renal epithelial cells from birds and mice: enhanced resistance of avian cells to oxidative stress and DNA damage. J. Gerontol. 53: B287–B292, 1998.CrossRefGoogle Scholar
  32. 32.
    Beckman K.B., Ames B.N.: The free radical theory of aging matures. Physiol. Rev. 78: 547–581, 1998.PubMedGoogle Scholar
  33. 33.
    Anson R.M., Croteau D.L., Stierum R.H., Fliburn C., Parsell R., Bohr V.A.: Homogeneous repair of singlet oxygen-induced DNA damage in differentially transcribed regions and strands of human mitochondrial DNA. Nucleic Acids Res. 26: 662–668, 1998.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Internal Publishing Switzerland 1999

Authors and Affiliations

  • A. Herrero
    • 1
  • G. Barja
    • 1
  1. 1.Departamento de Biología Animal-II, Facultad de BiologíaUniversidad ComplutenseMadridSpain

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