Advertisement

AGE

, Volume 32, Issue 3, pp 337–346 | Cite as

Influence of aerobic fitness on age-related lymphocyte DNA damage in humans: relationship with mitochondria respiratory chain and hydrogen peroxide production

  • Maria Paula MotaEmail author
  • Francisco M. Peixoto
  • Jorge F. Soares
  • Pedro A. Figueiredo
  • José C. Leitão
  • Isabel Gaivão
  • José A. Duarte
Article

Abstract

The aim of this study was to analyze the influence of aerobic fitness (AF) on age-related lymphocyte DNA damage in humans, giving special attention to the role of the mitochondrial respiratory chain and hydrogen peroxide production. Considering age and AF (as assessed by VO2max), 66 males (19–59 years old) were classified as high fitness (HF) or low fitness (LF) and distributed into one of the following groups: young adults (19–29 years old), adults (30–39 years old), and middle-aged adults (over 40 years old). Peripheral lymphocytes obtained at rest were used to assess DNA damage (strand breaks and formamidopyrimidine DNA glycosylase (FPG) sites through the comet assay), activity of mitochondrial complexes I and II (polarographically measured), and the hydrogen peroxide production rate (assayed by fluorescence). Results revealed a significant interaction between age groups and AF for DNA strand breaks (F = 8.415, p = .000), FPG sites (F = 11.766, p = .000), mitochondrial complex I activity (F = 7.555, p = .000), and H2O2 production (F = 7.500, p = .000). Except for mitochondrial complex II activity, the age variation of the remaining parameters was significantly attenuated by HF. Considering each AF level, an increase in DNA strand breaks and FPG sites with age (r = 0.655, p = 0.000, and r = 0.738, p = 0.000, respectively) was only observed in LF. Moreover, decreased mitochondrial complex I activity with age (r = −.470, p = .009) was reported in LF. These results allow the conclusion that high AF seems to play a key role in attenuating the biological aging process.

Keywords

DNA damage FPG sites Oxidative stress Mitochondrial respiratory chain Aging Exercise 

Notes

Acknowledgments

We are thankful to Dr. Andrew Collins (University of Oslo, Oslo Norway) for providing the comet assay protocol and the enzyme FPG.

Grants

This work was supported by a grant from the Fundação para a Ciência e Tecnologia (POCI/DES/62301/2004, POCI 2010, and FEDER).

References

  1. ACSM (American College of Sports Medicine Position Stand) (1998) Exercise and physical activity for older adults. Med Sci Sports Exerc 30(6):992–1008CrossRefGoogle Scholar
  2. Agarwal S, Sohal RS (1994) DNA oxidative damage and life expectancy in houseflies. Proc Natl Acad Sci USA 91(25):12332–12335CrossRefPubMedGoogle Scholar
  3. Ascensão A, Magalhaes J, Soares JM, Ferreira R, Neuparth MJ, Marques F et al (2005) Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis. Am J Physiol Heart Circ Physiol 289(2):H722–H731CrossRefPubMedGoogle Scholar
  4. Ascensão A, Ferreira R, Magalhaes J (2007) Exercise-induced cardioprotection: biochemical, morphological and functional evidence in whole tissue and isolated mitochondria. Int J Cardiol 117(1):16–30CrossRefPubMedGoogle Scholar
  5. Beckman KB, Ames BN (1998a) The free radical theory of aging matures. Physiol Rev 78(2):547–581PubMedGoogle Scholar
  6. Beckman KB, Ames BN (1998b) Mitochondrial aging: open questions. Ann N Y Acad Sci 854:118–127CrossRefPubMedGoogle Scholar
  7. Bradford MM (1976) Rapid and sensitive method for quantitation of microgram quantities of protein utilizing principle of protein-dye binding. Anal Biochem 72(1–2):248–254CrossRefPubMedGoogle Scholar
  8. Brierley EJ, Johnson MA, Lightowlers RN, James OF, Turnbull DM (1998) Role of mitochondrial DNA mutations in human aging: implications for the central nervous system and muscle. Ann Neurol 43(2):217–223CrossRefPubMedGoogle Scholar
  9. Bruce RA, Kusumi F, Hosmer D (1973) Maximal oxygen intake and nomographic assessment of functional aerobic impairment in cardiovascular disease. Am Heart J 85(4):546–562CrossRefPubMedGoogle Scholar
  10. Chakravarty EF, Hubert HB, Lingala VB, Fries JF (2008) Reduced disability and mortality among aging runners—a 21-year longitudinal study. Arch Intern Med 168(15):1638–1646CrossRefPubMedGoogle Scholar
  11. Chen JH, Hales CN, Ozanne SE (2007) DNA damage, cellular senescence and organismal ageing: causal or correlative? Nucleic Acids Res 35(22):7417–7428CrossRefPubMedGoogle Scholar
  12. Collins AR (2004) The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol 26(3):249–261CrossRefPubMedGoogle Scholar
  13. Cooke MS, Evans MD, Dizdaroglu M, Lunec J (2003) Oxidative DNA damage: mechanisms, mutation, and disease. Faseb J 17(10):1195–1214CrossRefPubMedGoogle Scholar
  14. Courneya KS, Karvinen KH (2007) Exercise, aging, and cancer. Appl Physiol Nutr Metab 32(6):1001–1007CrossRefPubMedGoogle Scholar
  15. den Hoed M, Hesselink MKC, van Kranenburg GPJ, Westerterp KR (2008) Habitual physical activity in daily life correlates positively with markers for mitochondrial capacity. J Appl Physiol 105(2):561–568CrossRefGoogle Scholar
  16. Figueiredo PA, Mota MP, Appell HJ, Duarte JA (2008) The role of mitochondria in aging of skeletal muscle. Biogerontology 9(2):67–84CrossRefPubMedGoogle Scholar
  17. Friedenreich CM (2001) Physical activity and cancer prevention: from observational to intervention research. Cancer Epidemiol Biomarkers Prev 10(4):287–301PubMedGoogle Scholar
  18. Friedenreich CM, Orenstein MR (2002) Physical activity and cancer prevention: etiologic evidence and biological mechanisms. J Nutr 132(11 Suppl):3456S–3464SPubMedGoogle Scholar
  19. Halliwell B (1999) Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition. Mutat Res 443(1–2):37–52PubMedGoogle Scholar
  20. Hudson EK, Hogue BA, Souza-Pinto NC, Croteau DL, Anson RM, Bohr VA et al (1998) Age-associated change in mitochondrial DNA damage. Free Radic Res 29(6):573–579CrossRefPubMedGoogle Scholar
  21. Judge S, Leeuwenburgh C (2007) Cardiac mitochondrial bioenergetics, oxidative stress, and aging. Am J Physiol Cell Physiol 292(6):C1983–C1992CrossRefPubMedGoogle Scholar
  22. Kohut ML, Senchina DS (2004) Reversing age-associated immunosenescence via exercise. Exerc Immunol Rev 10:6–41PubMedGoogle Scholar
  23. Krajcovicova-Kudlackova M, Valachovicova M, Paukova V, Dusinska M (2008) Effects of diet and age on oxidative damage products in healthy subjects. Physiol Res 57(4):647–651PubMedGoogle Scholar
  24. Kregel KC, Zhang HJ (2007) An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol 292(1):R18–R36PubMedGoogle Scholar
  25. Kruk J (2007) Physical activity in the prevention of the most frequent chronic diseases: an analysis of the recent evidence. Asian Pac J Cancer Prev 8(3):325–338PubMedGoogle Scholar
  26. Lee HC, Wei YH (2005) Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress. Int J Biochem Cell Biol 37(4):822–834CrossRefPubMedGoogle Scholar
  27. Lenaz G, D'Aurelio M, Pich MM, Geneva ML, Ventura B, Bovina C et al (2000) Mitochondrial bioenergetics in aging. Biochim Biophys Acta 1459(2–3):397–404PubMedGoogle Scholar
  28. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443(7113):787–795CrossRefPubMedGoogle Scholar
  29. Menshikova EV, Ritov VB, Fairfull L, Ferrell RE, Kelley DE, Goodpaster BH (2006) Effects of exercise on mitochondrial content and function in aging human skeletal muscle. J Gerontol A Biol Sci Med Sci 61(6):534–540PubMedGoogle Scholar
  30. Midgley AW, McNaughton LR, Polman R, Marchant D (2007) Criteria for determination of maximal oxygen uptake: a brief critique and recommendations for future research. Sports Med 37(12):1019–1028CrossRefPubMedGoogle Scholar
  31. Miller RA (1996) The aging immune system: primer and prospectus. Science 273(5271):70–74CrossRefPubMedGoogle Scholar
  32. Miro O, Alonso JR, Jarreta D, Casademont J, Urbano-Marquez A, Cardellach F (1999) Smoking disturbs mitochondrial respiratory chain function and enhances lipid peroxidation on human circulating lymphocytes. Carcinogenesis 20(7):1331–1336CrossRefPubMedGoogle Scholar
  33. Nakamoto H, Kaneko T, Tahara S, Hayashi E, Naito H, Radak Z et al (2007) Regular exercise reduces 8-oxodG in the nuclear and mitochondrial DNA and modulates the DNA repair activity in the liver of old rats. Exp Gerontol 42(4):287–295CrossRefPubMedGoogle Scholar
  34. Navarro A, Boveris A (2007) Brain mitochondrial dysfunction in aging: conditions that improve survival, neurological performance and mitochondrial function. Front Biosci 12:1154–1163CrossRefPubMedGoogle Scholar
  35. Nieman DC, Pedersen BK (1999) Exercise and immune function. Recent developments. Sports Med 27(2):73–80CrossRefPubMedGoogle Scholar
  36. Ozawa T (1995) Mitochondrial DNA mutations associated with aging and degenerative diseases. Exp Gerontol 30(3–4):269–290CrossRefPubMedGoogle Scholar
  37. Parise G, Phillips SM, Kaczor JJ, Tarnopolsky MA (2005) Antioxidant enzyme activity is up-regulated after unilateral resistance exercise training in older adults. Free Radic Biol Med 39(2):289–295CrossRefPubMedGoogle Scholar
  38. Pedersen BK, Hoffman-Goetz L (2000) Exercise and the immune system: regulation, integration, and adaptation. Physiol Rev 80(3):1055–1081PubMedGoogle Scholar
  39. Radak Z, Naito H, Kaneko T, Tahara S, Nakamoto H, Takahashi R et al (2002) Exercise training decreases DNA damage and increases DNA repair and resistance against oxidative stress of proteins in aged rat skeletal muscle. Pflugers Archiv 445(2):273–278CrossRefPubMedGoogle Scholar
  40. Radak Z, Kumagai S, Nakamoto H, Goto S (2007) 8-Oxoguanosine and uracil repair of nuclear and mitochondrial DNA in red and white skeletal muscle of exercise-trained old rats. J Appl Physiol 102(4):1696–1701CrossRefPubMedGoogle Scholar
  41. Radak Z, Atalay M, Jakus J, Boldogh I, Davies K, Goto S (2009) Exercise improves import of 8-oxoguanine DNA glycosylase into the mitochondrial matrix of skeletal muscle and enhances the relative activity. Free Radic Biol Med 46(2):238–243CrossRefPubMedGoogle Scholar
  42. Randerath K, Randerath E, Filburn C (1996) Genomic and mitochondrial DNA alterations with aging. In: Schneider EL, Rowe JW (eds) Handbook of the biology of aging, 4th edn. Academic Press, New York, pp 198–209Google Scholar
  43. Ross OA, Hyland P, Curran MD, McIlhatton BP, Wikby A, Johansson B et al (2002) Mitochondrial DNA damage in lymphocytes: a role in immunosenescence? Exp Gerontol 37(2–3):329–340CrossRefPubMedGoogle Scholar
  44. Rustin P, Chretien D, Bourgeron T, Gerard B, Rotig A, Saudubray JM et al (1994) Biochemical and molecular investigations in respiratory-chain deficiencies. Clin Chim Acta 228(1):35–51CrossRefPubMedGoogle Scholar
  45. Shvartz E, Reibold RC (1990) Aerobic fitness norms for males and females aged 6 to 75 years: a review. Aviat Space Environ Med 61(1):3–11PubMedGoogle Scholar
  46. Starnes JW, Taylor RP (2007) Exercise-induced cardioprotection: endogenous mechanisms. Med Sci Sports Exerc 39(9):1537–1543CrossRefPubMedGoogle Scholar
  47. Valletta EA, Berton G (1987) Desensitization of macrophage oxygen-metabolism on immobilized ligands: different effect of immunoglobulin-G and complement. J Immunol 138(12):4366–4373PubMedGoogle Scholar
  48. Venditti P, Masullo P, Di Meo S (1999) Effect of training on H(2)O(2) release by mitochondria from rat skeletal muscle. Arch Biochem Biophys 372(2):315–320CrossRefPubMedGoogle Scholar
  49. Ventura B, Genova ML, Bovina C, Formiggini G, Lenaz G (2002) Control of oxidative phosphorylation by complex I in rat liver mitochondria: implications for aging. Biochim Biophys Acta 1553(3):249–260CrossRefPubMedGoogle Scholar
  50. Wallace DC (2005) Mitochondria and cancer: warburg addressed. Cold Spring Harb Symp Quant Biol 70:363–374CrossRefPubMedGoogle Scholar
  51. Wei YH, Lee HC (2002) Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp Biol Med (Maywood) 227(9):671–682Google Scholar

Copyright information

© American Aging Association, Media, PA, USA 2010

Authors and Affiliations

  • Maria Paula Mota
    • 1
    Email author
  • Francisco M. Peixoto
    • 2
  • Jorge F. Soares
    • 1
  • Pedro A. Figueiredo
    • 3
  • José C. Leitão
    • 1
  • Isabel Gaivão
    • 2
  • José A. Duarte
    • 4
  1. 1.University of Trás-os-Montes and Alto Douro, Centro de Investigação em Desporto, Saúde e Desenvolvimento HumanoVila RealPortugal
  2. 2.University of Trás-os-Montes and Alto Douro, Centro de Ciência Animal e VeterináriaVila RealPortugal
  3. 3.Instituto Superior da Maia, Centro de Investigação em Actividade Física, Saúde e LazerPortoPortugal
  4. 4.Faculty of Sports, Centro de Investigação em Actividade Física, Saúde e LazerPortoPortugal

Personalised recommendations