Mitochondria and Immunosenescence

  • Pazit Beckerman
  • Arie Ben Yehuda

The immune system undergoes age-associated changes, that affect its response to infections and cancer, and contributes to the organism’s aging and its associated pathologies. An eminent hypothesis to explain the aging process, most supported by experimental data, is the mitochondrial free radical theory. Evidence is accumulating, linking mitochondrial oxidative damage and apoptosis to immunosenescence.


Mitochondrial Membrane Potential Mitochondrial Permeability Transition Mitochondrial Permeability Transition Pore Replicative Senescence Increase Reactive Oxygen Species Production 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Lesnefsky EJ, Hoppel CL (2006) Oxidative phosphorylation and aging. Ageing Res Rev. 5(4):402–433PubMedCrossRefGoogle Scholar
  2. Weiss JN, Korge P, Honda HM, Ping P (2003) Role of the mitochondrial permeability transition in myocardial disease. Circ Res 93(4):292–301PubMedCrossRefGoogle Scholar
  3. Swerdlow RH, Parks JK, Miller SW, Tuttle JB, Trimmer PA, Sheehan JP, Bennett JP, Davis RE, Parker WD (1996) Origin and functional consequences of the complex I defect in Parkinson’s disease. Ann Neurol 40(4):663–671PubMedCrossRefGoogle Scholar
  4. Schapira AH, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54(3):823–827PubMedCrossRefGoogle Scholar
  5. Gu M, Cooper JM, Taanman JW, Schapira AH (1998) Mitochondrial DNA transmission of the mitochondrial defect in Parkinson’s disease. Ann Neurol 44(2):177–186PubMedCrossRefGoogle Scholar
  6. Yoshino H, Nakagawa-Hattori Y, Kondo T, Mizuno Y (1992) Mitochondrial complex I and II activities of lymphocytes and platelets in Parkinson’s disease. J Neural Transm Park Dis Dement Sect 4(1):27–34PubMedCrossRefGoogle Scholar
  7. Shults CW, Oakes D, Kieburtz K, Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M (2002) Parkinson Study Group. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 59(10):1541–1550PubMedCrossRefGoogle Scholar
  8. Casley CS, Canevari L, Land JM, Clark JB, Sharpe MA (2002) Beta-amyloid inhibits integrated mitochondrial respiration and key enzyme activities. J Neurochem. 80(1):91–100PubMedCrossRefGoogle Scholar
  9. Schapira AH (2006) Mitochondrial disease. Lancet. 368(9529):70–82PubMedCrossRefGoogle Scholar
  10. Crompton M (1999) The mitochondrial permeability transition pore and its role in cell death. Biochem J. 341(2):233–249PubMedCrossRefGoogle Scholar
  11. Lenaz G, Baracca A, Fato R, Genova ML, Solaini G (2006) New insights into structure and function of mitochondria and their role in aging and disease. Antioxid Redox Signal 8(3-4):417–437PubMedCrossRefGoogle Scholar
  12. Cavazzoni M, Barogi S, Baracca A, Parenti Castelli G, Lenaz G (1999) The effect of aging and an oxidative stress on peroxide levels and the mitochondrial membrane potential in isolated rat hepatocytes. FEBS Lett 449(1):53–56PubMedCrossRefGoogle Scholar
  13. 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):312–318PubMedGoogle Scholar
  14. Fraker PJ, Lill-Elghanian DA (2004) The many roles of apoptosis in immunity as modified by aging and nutritional status. J Nutr Health Aging 8(1):56–63PubMedGoogle Scholar
  15. Sohal R, Weindruch R (1996) Oxidative stress, caloric restriction, and aging. Science 273(5271):59–63PubMedCrossRefGoogle Scholar
  16. Sanz A, Pamplona R, Barja G (2006) Is the mitochondrial free radical theory of aging intact? Antioxid Redox Signal 8(3–4):582–599Google Scholar
  17. Hayakawa M, Katsumata K, Yoneda M, Tanaka M, Sugiyama S, Ozawa T (1996) Age-related extensive fragmentation of mitochondrial DNA into minicircles. Biochem Biophys Res Commun 226(2):369–377PubMedCrossRefGoogle Scholar
  18. Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly YM, Gidlof S, Oldfors A, Wibom R, Tornell J, Jacobs HT, Larson NG (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429(6990):417–423PubMedCrossRefGoogle Scholar
  19. Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA et al. (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309(5733):481–484PubMedCrossRefGoogle Scholar
  20. Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308(5730):1909–1911PubMedCrossRefGoogle Scholar
  21. Chan DC (2006) Mitochondria: dynamic organelles in disease, aging, and development. Cell. 125(7):1241–1252PubMedCrossRefGoogle Scholar
  22. Beregi E, Regius O (1983) Relationship of mitochondrial damage in human lymphocytes and age. Aktuelle Gerontol 13(6):226–228PubMedGoogle Scholar
  23. Murasko DM, Weiner P, Kaye D (1987) Decline in mitogen induced proliferation of lymphocytes with increasing age. Clin Exp Immunol 70(2):440–448PubMedGoogle Scholar
  24. Chaudhri G, Clark IA, Hunt NH, Cowden WB, Ceredig R (1986) Effect of antioxidants on primary alloantigen-induced T cell activation and proliferation. J Immunol 137(8):2646–2652PubMedGoogle Scholar
  25. Verity MA, Tam CF, Cheung MK, Mock DC, Walford RL (1983) Delayed phytohemagglutinin- stimulated production of adenosine triphosphate by aged human lymphocytes: possible relation to mitochondrial dysfunction. Mech Ageing Dev 23(1):53–65PubMedCrossRefGoogle Scholar
  26. Weindruch RH, Cheung MK, Verity MA, Walford RL (1980) Modification of mitochondrial respiration by aging and dietary restriction. Mech Ageing Dev 12(4):375–392PubMedCrossRefGoogle Scholar
  27. Witkowski J, Micklem HS (1985) Decreased membrane potential of T lymphocytes in ageing mice: flow cytometric studies with a carbocyanine dye. Immunology 56(2):307–313PubMedGoogle Scholar
  28. Leprat P, Ratinaud MH, Julien R (1990) A new method for testing cell ageing using two mitochondria specific fluorescent probes. Mech Ageing Dev 52(2–3):149–167PubMedCrossRefGoogle Scholar
  29. Pieri C, Recchioni R, Moroni F (1993) Age-dependent modifications of mitochondrial transmembrane potential and mass in rat splenic lymphocytes during proliferation. Mech Ageing Dev 70(3):201–212PubMedCrossRefGoogle Scholar
  30. Rottenberg H, Wu S (1997) Mitochondrial dysfunction in lymphocytes from old mice: enhanced activation of the permeability transition. Biochem Biophys Res Commun 240(1):68–74PubMedCrossRefGoogle Scholar
  31. Tsai K, Hsu TG, Lu FJ, Hsu CF, Liu TY, Kong CW (2001) Age-related changes in the mitochondrial depolarization induced by oxidative injury in human peripheral blood leukocytes. Free Radic Res 35(4):395–403PubMedCrossRefGoogle Scholar
  32. Pawelec G, Adibzadeh M, Solana R, Beckman I (1997) The T cell in the ageing individual. Mech Ageing Dev 93(1–3):35–45PubMedCrossRefGoogle Scholar
  33. Sulger J, Dumais-Huber C, Zerfass R, Henn FA, Aldenhoff JB (1999 Mar) The calcium response of human T lymphocytes is decreased in aging but increased in Alzheimer’s dementia. Biol Psychiatry 45(6):737–742PubMedCrossRefGoogle Scholar
  34. Mather MW, Rottenberg H (2002) The inhibition of calcium signaling in T lymphocytes from old mice results from enhanced activation of the mitochondrial permeability transition pore. Mech Ageing Dev 123(6):707–724PubMedCrossRefGoogle Scholar
  35. Lepple-Wienhues A, Belka C, Laun T, Jekle A, Walter B, Wieland U, Welz M, Heil L, Kun J, Busch G, Weller M, Bamberg M, Gulbins E, Lang F (1999) Stimulation of CD95 (Fas) blocks T lymphocyte calcium channels through sphingomyelinase and sphingolipids. Proc Natl Acad Sci U S A 96(24):13795–13800PubMedCrossRefGoogle Scholar
  36. Ayub K, Laffafian I, Dewitt S, Hallett MB (2004) Ca influx shutdown in neutrophils induced by Fas (CD95) cross-linking. Immunology 112(3):454–460PubMedCrossRefGoogle Scholar
  37. Ayub K, Hallett MB (2004) Signalling shutdown strategies in aging immune cells. Aging Cell 3(4):145–149PubMedCrossRefGoogle Scholar
  38. Drouet M, Lauthier F, Charmes JP, Sauvage P, Ratinaud MH (1999) Age-associated changes in mitochondrial parameters on peripheral human lymphocytes. Exp Gerontol. 34(7):843–852PubMedCrossRefGoogle Scholar
  39. Sandhu SK, Kaur G (2003) Mitochondrial electron transport chain complexes in aging rat brain and lymphocytes. Biogerontology 4(1):19–29PubMedCrossRefGoogle Scholar
  40. Zamzami NP, Marchetti P, Castedo M, Zanin C, Vayssiere JL, Petit PX, Kroemer G (1995) Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo. J Exp Med 181(5):1661–1672PubMedCrossRefGoogle Scholar
  41. Petit PX, LeCoeur H, Zorn E, Dauguet C, Mignotte B, Gougeon ML (1995) Alterations in mitochondrial structure, function are early events of dexamethasone-induced thymocyte apoptosis. J Cell Biol 130(1):157–567PubMedCrossRefGoogle Scholar
  42. Marchetti P, Hirsch T, Zamzami N, Castedo M, Decaudin D, Susin SA, Masse B, Kroemer G (1996) Mitochondrial permeability transition triggers lymphocyte apoptosis. J Immunol 157(11):4830–4836PubMedGoogle Scholar
  43. Arnold R, Brenner D, Becker M, Frey CR, Krammer PH, (2006) How T lymphocytes switch between life and death. Eur J Immunol 36(7):1654–1658PubMedCrossRefGoogle Scholar
  44. Spaulding C, Guo W, Effros RB, et al. (1999) Resistance to apoptosis in human CD8+ T-cells that reach replicative senescence after multiple rounds of antigen-specific proliferation. Exp Gerontol 34(5):633–644PubMedCrossRefGoogle Scholar
  45. Monti D, Salvioli S, Capri M, Malorni W, Straface E, Cossarizza A, Botti B, Piacentini M, Baggio G, Barbi C, Valensin S, Bonafe M, Franceschi C (2000) Decreased susceptibility to oxidative stress-induced apoptosis of peripheral blood mononuclear cells from healthy elderly, centenarians. Mech Ageing Dev 121(1–3):239–250PubMedGoogle Scholar
  46. Gupta S (2000) Molecular and biochemical pathways of apoptosis in lymphocytes from aged humans. Vaccine 18(16):1596–1601PubMedCrossRefGoogle Scholar
  47. Aggarwal S, Gupta S (1998) Increased apoptosis of T-cell subsets in aging humans: altered expression of Fas (CD95), Fas ligand, Bcl-2, Bax J Immunol 160(4):1627–1637PubMedGoogle Scholar
  48. Gupta S, Gollapudi S (2006) Molecular mechanisms of TNF-alpha-induced apoptosis in naive, memory T cell subsets. Autoimmun Rev 5(4):264–268PubMedCrossRefGoogle Scholar
  49. Kim HJ, Nel AE (2005) The role of phase II antioxidant enzymes in protecting memory T-cells from spontaneous apoptosis in young and old mice. J Immunol 175(5):2948–2959PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Pazit Beckerman
    • 1
  • Arie Ben Yehuda
    • 1
  1. 1.The Department of MedicineUniversity Hospital KeremKerem

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