Journal of Applied Genetics

, Volume 50, Issue 1, pp 55–62 | Cite as

Mitochondria and aging: innocent bystanders or guilty parties?

  • K. Tońska
  • A. Sołyga
  • E. Bartnik
Review Article


There are many theories of aging and a number ofthem encompass the role of mitochondria in this process. Mitochondrial DNA mutations and deletions have been shown to accumulate in many tissues in mammals during aging. However, there is little evidence that these mutations could affect the functioning of aging tissues.


mitochondria mitochondrial DNA reactive oxygen species skin aging 


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  1. Ahmed S, Passos JF, Birket MJ, Beckmann T, Brings S, Peters H, et al. 2008. Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress. J Cell Sci 121: 1046–1053.CrossRefPubMedGoogle Scholar
  2. Amo T, Brand MD, 2007. Were inefficient mitochondrial haplogroups selected during migrations of modern humans? A test using modular kinetic analysis of coupling in mitochondria from cybrid cell lines. Biochem J: 404: 345–351.CrossRefPubMedGoogle Scholar
  3. Amo T, Yadava N, Oh R, Nicholls DG, Brand MD, 2008. Experimental assessment of bioenergetic differences caused by the common European mitochondrial DNA haplogroups H and T. Gene. 411: 69–76.CrossRefPubMedGoogle Scholar
  4. Balaban RS, Nemoto S, Finkel T, 2005. Mitochondria, oxidants and aging. Cell 120: 483–495.CrossRefPubMedGoogle Scholar
  5. Berneburg M, Gattermann N, Stege H, 1997. Chronically ultraviolet-exposed humanskinshowsa higher mutation frequencyofmitochondrial DNA as compared to unexposed skin and the hematopoietic system. Photochem Photobiol 66: 271–275.CrossRefPubMedGoogle Scholar
  6. Berneburg M, Grether-Beck S, Kurten V, Ruzicka T, Briviba K, Sies H, Krutmann J, 1999. Singlet oxygen mediates the UVA-induced generation of the photoaging-associated mitochondrial common deletion, J Biol Chem 274: 15345–15349.CrossRefPubMedGoogle Scholar
  7. Berneburg M, Plettenberg H, Medve-Konig K, Pfahlberg A, Gers-Barlag H, Gefeller O, Krutmann J, 2004. Induction of the photoaging-associated mito-chondrial common deletionin vivoinnormal human skin. J Invest Dermatol 122: 1277–1283.CrossRefPubMedGoogle Scholar
  8. Berneburg M, Kamenisch Y, Krutmann J, Rucken M, 2006. To repair or not to repair — no longer a question: repair of mitochondrial DNA shielding against age and cancer. Exp Dermatol 15: 1005–1015.CrossRefPubMedGoogle Scholar
  9. Birch-Machin MA, 2000. Mitochondria and skin disease. Clin Exp Dermatol 25: 141–146.CrossRefPubMedGoogle Scholar
  10. Birket MJ, Birch-Machin MA, 2007. Ultraviolet radiation exposure accelerates the accumulation of the aging-dependent T414G mitochondrial DNA mutation in human skin. Aging Cell 2007 6: 557–564.CrossRefPubMedGoogle Scholar
  11. Chinnery PF, Taylor GA, Howell N, Brown DT, Parsons TJ, Turnbull DM, 2001. Point mutations of the mtDNA control region in normal and neurodegenerative human brains. 68: 529–532.Google Scholar
  12. Coskun PE, Flint Beal M, Wallace DC, 2004. Alzheimer’s brains harbor somatic mtDNA control mutations that suppress mitochondrial transcription and replication. Proc Natl Acad Sci USA 101: 10726–10731.CrossRefPubMedGoogle Scholar
  13. Dahmani Y, Marcuello A, Díez-Sanchez C, Ruiz-Pesini E, Montoya J, López-Pérez MJ, 2008. Association of human mitochondrial DNA variants with plasma LDL levels. Mitochondrion 8: 247–253.CrossRefPubMedGoogle Scholar
  14. De Benedictis G, Rose G, Carrieri G, De Luca M, Falcone E, Passarino G, et al. 1999. Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans. FASEB J 13: 1532–1536.PubMedGoogle Scholar
  15. Dufour E, Terzioglu M, Sterky FH, Soerensen L, Galter D, Olson L, et al. 2008. Age-associated mosaic respiratory chain deficiency causes trans-neuronal degeneration. Hum Mol Genet 17: 1418–1426.CrossRefPubMedGoogle Scholar
  16. Elson JE, Turnbull DM, Taylor RW, 2007. Testing the adaptive selection of human mtDNA haplogroups: an experimental bioenergetics approach. Biochem J 404: e3-e5.CrossRefPubMedGoogle Scholar
  17. Harbottle A, Birch-Machin MA, Michikawa Y, Mazzucchelli F, Bresolin N, Scarlato G, Attardi G, 1999. Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication. Science 286: 774–779.CrossRefGoogle Scholar
  18. Harman D, 1956. Aging: a theory based on free radical and radiation chemistry. J Gerontol 11: 298–300.PubMedGoogle Scholar
  19. Johnson FB, Sinclair DA, Guarente L, 1999. Molecular biology of aging. Cell 96: 291–302.CrossRefPubMedGoogle Scholar
  20. Jou MJ, Peng TI, Wu HY, Wei YH, 2005. Enhanced generation of mitochondrial reactive oxygen species in cybrids containing 4977-bp mitochondrial DNA deletion. Ann NY Acad Sci 1042: 221–228.CrossRefPubMedGoogle Scholar
  21. Khrapko K, Kraytsberg Y, de Grey AD, Vijg J, Schon EA, 2006. Does premature aging of the mtDNA mutator mouse prove that mtDNA mutations are involved in natural aging? Aging Cell 5: 279–282.CrossRefPubMedGoogle Scholar
  22. King MP, Attardi G, 1989. Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science 246: 500–503.CrossRefPubMedGoogle Scholar
  23. Kirkwood TBL, 2005. Understanding the odd science of aging. Cell 120: 437–447.CrossRefPubMedGoogle Scholar
  24. Krishnan KJ, Greaves LC, Reeve AK, Turnbull D, 2007. The ageing mitochondrial genome. Nucl Acids Res 35: 7399–7405.CrossRefPubMedGoogle Scholar
  25. Krishnan KJ, Harbottle A, Birch-Machin MA, 2004. The Use of a 3895 bp mitochondrial DNA deletion as a marker for sunlight exposure in human skin, J Invest Dermatol 123: 1020–1024.CrossRefPubMedGoogle Scholar
  26. Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, et al. 2005. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309: 481–484.CrossRefPubMedGoogle Scholar
  27. Kukat A, Kukat C, Brocher J, Schäfer I, Krohne G, Trounce IA, et al. 2008. Generation of rho0 cells utilizing a mitochondrially targeted restriction endonuclease and comparative analyses. Nucleic Acids Res. 2008;36: e44. Epub 2008 Mar 19.CrossRefPubMedGoogle Scholar
  28. Lightowlers RN, Jacobs HT, Kajander OA. 1999. Mitochondrial DNA — all things bad? Trends Genet 15: 91–93.CrossRefPubMedGoogle Scholar
  29. Lu CY, Lee HC, Fahn HJ, Wei YH, 1999. Oxidative damage elicited by imbalance of free radical scavenging enzymes is associated with large-scale mtDNA deletions in aging human skin. Mutat Res 423: 11–21.PubMedGoogle Scholar
  30. Lu CY, Lee CF, Wei YH, 2007. Quantitative effect of 4977 bp deletion of mitochondrial DNA on the susceptibility of human cells to UV-induced apoptosis. Mitochondrion 7: 89–95.CrossRefGoogle Scholar
  31. Liu VWS, Zhang C, Nagley P, 1998. Mutations in mitochondrial DNA accumulate differentially in three human tissues during aging. Nucleic Acids Res 26: 1268–1275.CrossRefPubMedGoogle Scholar
  32. Moraes CT, Ricci E, Petruzzella V, Shanske S, DiMauro S, Schon EA, Bonilla E, 1992. Molecular analysis of the muscle pathology associated with mitochondrial DNA deletions. Nat Genet 1: 359–367.CrossRefPubMedGoogle Scholar
  33. Murdock DG, Christacos NC, Wallace DC., 2000. The age-related accumulation of a mitochondrial DNA control region mutation in muscle, but not brain, detected by a sensitive PNA-directed PCR clamping based method. Nucleic Acids Res 28: 4350–4355.CrossRefPubMedGoogle Scholar
  34. Nakahara H, Kanno T, Inai Y, Utsumi K, Hiramatsu M, Mori A, Packer L, 1998. Mitochondrial dysfunction in the senescence accelerated mouse (SAM). Free Radic Biol Med 4: 85–92.CrossRefGoogle Scholar
  35. Nekhaeva E, Bodyak ND, Kraytsberg Y, McGrath SB, Van Orsouw NJ, Pluzhnikov A, et al. 2002. Clonally expanded mtDNA point mutations are abundant in individual cells of human tissues. Proc Natl Acad Sci U S A 99: 5521–5526.CrossRefPubMedGoogle Scholar
  36. Passos JF, Saretzki G, Ahmed S, Nelson G, Richter T, Peters H, et al. 2007. Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biol. 5: e110.CrossRefPubMedGoogle Scholar
  37. Peng TI, Yu PR, Chen JY, Wang HL, Wu HY, Wei YH, Jou MJ, 2006. Visualizing common deletion of mitochondrial DNA-augmented mitochondrial reactive oxygen species generation and apoptosis upon oxidative stress. Biochim Biophys Acta 1762: 241–255.PubMedGoogle Scholar
  38. Pesce V, Cormio A, Fracasso F, Vecchiet J, Felzani G, Lezza AMS, et al. 2001. Age-related mitochondrial genotypic and phenotypic alterations in human skeletal muscle. Free Rad Biol Med 30: 1–11.CrossRefGoogle Scholar
  39. Puizina-Ivić N, 2008. Skin aging. Acta Dermatovenerol Alp Panonica Adriat. 17: 47–54.PubMedGoogle Scholar
  40. Ray AJ, Turner R, Nikaido O, Rees JL, Birch-Machin MA, 2000. The spectrum of mitochondrial DNA deletions is a ubiquitous marker of ultraviolet radiation exposure in human skin. J Invest Dermatol 115: 674–679.CrossRefPubMedGoogle Scholar
  41. Samuels DC, 2005. Mitochondrial DNA repeats constrain the life span of mammals. Trends Genet 20: 226–228.CrossRefGoogle Scholar
  42. Samuels DC, Carothers AD, Horton R, Chinnery PF, 2006. The power to detect disease associations with mitochondrial DNA haplogroups. Am J Hum Genet 78: 713–720.CrossRefPubMedGoogle Scholar
  43. Santoro A, Salvioli S, Raule N, Capri M, Sevini S, Valensin S, et al. 2006. Mitochondrial DNA involvement in human longevity. Biochim Biophys Acta 1757: 1388–1399.CrossRefPubMedGoogle Scholar
  44. Sawyer DE, Van Houten B, 1999. Repair of DNA damage in mitochondria. Mutat Res 434: 161–176PubMedGoogle Scholar
  45. Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, et al. 2005. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308: 1909–1911.CrossRefPubMedGoogle Scholar
  46. Sedensky MM, Morgan PG, 2006 Mitochondrial respiration and reactive oxygen species in mitochondrial aging mutants. Exp Gerontol 41: 237–45.CrossRefPubMedGoogle Scholar
  47. Seibel P, Di Nunno C, Kukat C, Schäfer I, Del Bo R, Bordoni A, et al. 2008. Cosegregation of novel mitochondrial 16S rRNA gene mutations with the age-associated T414G variant in human cybrids. Nucleic Acids Res. Sep 16. [Epub ahead of print] PMID: 18796524 doi:10.1993/nar/gkn592Google Scholar
  48. Shoffner JM, Lott MT, Voljavec AS, Soueidan SA, Costigan DA, Wallace DC, 1989. Spontaneous Kearns-Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion: a slip-replication model and metabolic therapy. Proc Natl Acad Sci USA 86: 7952–7956.CrossRefPubMedGoogle Scholar
  49. Speakman JR, Talbot DA, Selman C, Snart S, McLaren JS, Redman P, et al. 2004. Uncoupled and surviving: individual mice with high metabolism have higher mitochondrial uncoupling and live longer. Aging Cell 3: 87–95.CrossRefPubMedGoogle Scholar
  50. Takeda T, 1999. Senescence-accelerated mouse (SAM): a biogerontological resource in aging research. Neurobiol Aging. 20: 105–110.CrossRefPubMedGoogle Scholar
  51. Trifunovic A, Hansson A, Wredenberg A, Rovio AT, Dufour E, Khvorostov I, et al. 2005. Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci U S A 102: 17993–17998.CrossRefPubMedGoogle Scholar
  52. Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, et al. 2004. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429: 417–423.CrossRefPubMedGoogle Scholar
  53. Vermulst M, Wanagat J, Kujoth GC, Bielas JH, Rabinovitch PS, Prolla TA, Loeb LA, 2008. DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice. Nat Genet 40: 392–4.CrossRefPubMedGoogle Scholar
  54. Wallace DC, 2005. A mitochondrial paradigm of metabolic and degenerative diseases, aging and cancer: a dawn for evolutionary medicine. Annu Rev Genet 39: 359–407.CrossRefPubMedGoogle Scholar
  55. Wei YH, Ma YS, Lee HC, Lee CF, Lu CY, 2001. Mitochondrial theory of aging matures: roles of mtDNA mutation and oxidative stress in human aging. Zhonghua Yi Xue Za Zhi 64: 259–270.PubMedGoogle Scholar
  56. Yakes FM, van Houten B, 1997. Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci U S A 94: 514–519.CrossRefPubMedGoogle Scholar
  57. Zegarska B, Woźniak M, 2006. Reasons of endogenous aging of the skin. Geront Pol 14: 153–159.Google Scholar

Copyright information

© Institute of Plant Genetics, Polish Academy of Sciences, Poznan 2009

Authors and Affiliations

  1. 1.Department of Genetics and Biotechnology, Biology FacultyUniversity of WarsawWarsawPoland
  2. 2.Institute of Biochemistry and BiophysicsWarsawPoland

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