Skip to main content
SpringerLink
Log in
Book cover

Mitochondrial DNA Mutations in Aging, Disease and Cancer pp 205–238Cite as

Mitochondrial DNA Mutations in Aging

  • Chapter

Abstract

Human aging is characterized by the progressive decline in function at the levels of cells, tissues and organs. Various proposals have been put forward to explain the basis of aging, but the different processes envisaged should not be considered as mutually exclusive. The most prominent mechanisms proposed include genetic programming of senescence, damage to macromolecules by free radicals, molecular crosslinking, changes in immunological function, telomere shortening and somatic genetic changes in DNA.1’2 Among these mechanisms, the contribution of mitochondrial DNA (mtDNA) mutations to the aging process, with consequential changes in cellular bioenergetic functions, has attracted wide attention in recent years (for reviews, see refs. 3–8).

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Harman D. The aging process: Major risk factor for disease and death. Proc Natl Acad Sci USA 1991; 88: 5360–5363.

    PubMed  CAS  Google Scholar 

  2. Kirkwood TBL. Human senescence. BioEssays 1996; 18: 1009–1016.

    PubMed  CAS  Google Scholar 

  3. Linnane AW, Marzuki S, Ozawa T et al. Mitochondrial DNA mutations as an important contributor to aging and degenerative diseases. Lancet 1989; 1: 642–645.

    PubMed  CAS  Google Scholar 

  4. Linnane AW, Zhang C, Baumer A et al. Mitochondrial DNA mutation and the aging process: Bioenergy and pharmacological intervention. Mutation Res 1992; 275: 95–208.

    Google Scholar 

  5. Wei Y-H. Mitochondrial DNA alterations as aging-associated molecular events. Mutation Res 1992; 275: 145–155.

    PubMed  CAS  Google Scholar 

  6. Wallace DC. Mitochondrial genetics: A paradigm for aging and degenerative diseases? Science 1992; 256: 628–632.

    PubMed  CAS  Google Scholar 

  7. Shoffner JM, Wallace DC. Oxidative phosphorylation diseases. In: Scriver CR, Beaudet AL, Sly WS et al. eds. The metabolic and molecular bases of inherited disease. 7th ed. New York: McGraw-Hill, 1995: 1535–1610.

    Google Scholar 

  8. Papa S. Mitochondria oxidative phosphorylation changes in the life span. Molecular aspects and physiopathological implications. Biochim Biophys Acta 1996; 1276: 87–105.

    PubMed  Google Scholar 

  9. Anderson S, Bankier AT, Barrel BG et al. Sequence and organization of the human mitochondrial genome. Nature 1981; 290: 457–465.

    PubMed  CAS  Google Scholar 

  10. Attardi G, Schatz G. Biogenesis of mitochondria. Ann Rev Cell Biol 1988; 4: 289–333.

    PubMed  CAS  Google Scholar 

  11. Richter C, Park J-W, Ames BN. Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc Natl Acad Sci USA 1988; 85: 6465–6467.

    PubMed  CAS  Google Scholar 

  12. Harman D. Free radical theory of aging: Consequences of mitochondrial aging. Age 1983; 6: 86–94.

    CAS  Google Scholar 

  13. Miguel J. An integrated theory of aging as the result of mitochondrial-DNA mutation in differentiated cells. Arch Gerontol Geriatr 1991; 12: 99–117.

    Google Scholar 

  14. Bandy B, Davison AJ. Mitochondrial mutations may increase oxidative stress: Implications for carcinogenesis and aging? Free Radical Biol Med 1990; 8: 523–539.

    CAS  Google Scholar 

  15. Ozawa T. Mechanism of somatic mitochondrial DNA mutations associated with age and diseases. Biochim Biophys Acta 1995; 1271: 77–189.

    Google Scholar 

  16. Holt IJ, Harding AE, Morgan-Hughes JA. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 1988; 331: 717–719.

    PubMed  CAS  Google Scholar 

  17. Zeviani M, Moraes CT, DiMauro S et al. Deletions of mitochondrial DNA in Kearns-Sayre syndrome. Neurology 1988; 38: 1339–1346.

    PubMed  CAS  Google Scholar 

  18. McShane MA, Hammans SR, Sweeney M et al. Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA. Am J Hum Genet 1991; 48: 39–42.

    PubMed  CAS  Google Scholar 

  19. Schon EA, Rizzuto R, Moraes CT et al. A direct repeat is a hotspot for large-scale deletion of human mitochondrial DNA. Science 1989; 244: 346–349.

    PubMed  CAS  Google Scholar 

  20. Vaillant F, Nagley P. Human cell mutants with very low mitochondrial DNA copy number (pd). Hum Mol Genet 1995; 4: 903–914.

    PubMed  CAS  Google Scholar 

  21. Linnane AW, Baumer A, Maxwell RJ et al. Mitochondrial gene mutation: The aging process and degenerative diseases. Biochem Int 1990; 22: 1067–1076.

    PubMed  CAS  Google Scholar 

  22. Cortopassi GA, Arnheim N. Detection of a specific mitochondrial DNA deletion in tissues of older humans. Nucleic Acids Res 1990; 18:6927–6933•

    Google Scholar 

  23. Yen T-C, Su J-H, King K-L et al. Aging-associated 5 kb deletion in human liver mitochondrial DNA. Biochem Biophys Res Commun 1991; 178: 124–131.

    PubMed  CAS  Google Scholar 

  24. Corral-Debrinski M, Stepien G, Shoffner JM et al. Hypoxemia is associated with mitochondrial DNA damage and gene induction. J Am Med Assoc 1991; 266: 1812–1816.

    CAS  Google Scholar 

  25. Corral-Debrinski M, Horton T, Lott MT et al. Mitochondrial DNA deletions in human brain: Regional variability and increase with advanced age. Nature Genet 1992; 2: 324–329.

    PubMed  CAS  Google Scholar 

  26. Soong NW, Hinton DR, Cortopassi G et al. Mosaicism for a specific somatic mitochondrial DNA mutation in adult human brain. Nature Genet 1992; 2: 318–323.

    PubMed  CAS  Google Scholar 

  27. Cortopassi G, Shibata D, Soong NW et al. A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proc Natl Acad Sci USA 1992; 89: 7370–7374.

    PubMed  CAS  Google Scholar 

  28. Zhang C, Baumer A, Maxwell RJ et al. Multiple mitochondrial DNA deletions in an elderly human individual. FEBS Lett 1992; 297: 34–38.

    PubMed  CAS  Google Scholar 

  29. Simonetti S, Chen X, DiMauro S et al. Accumulation of deletions in human mitochondrial DNA during normal aging: Analysis by quantitative PCR. Biochim Biophys Acta 1992; 1180: 113–122.

    PubMed  CAS  Google Scholar 

  30. Baumer A, Zhang C, Linnane AW et al. Age-related human mtDNA deletions: A heterogenous set of deletions arising at a single pair of directly repeated sequences. Am J Hum Genet 1994; 54: 618–630.

    PubMed  CAS  Google Scholar 

  31. Lee H-C, Pang C-Y, Hsu H-S et al. Differential accumulation of 4977 bp deletion in mitochondrial DNA of various tissues in human aging. Biochim Biophys Acta 1994; 1226: 37–43.

    PubMed  CAS  Google Scholar 

  32. Ikebe S-i, Tanaka M, Ohno K et al. Increase of deleted mitochondrial DNA in the striatum in Parkinson’s disease and senescence. Biochem Biophys Res Commun 1990; 170: 1044–1048.

    Google Scholar 

  33. Ozawa T, Tanaka M, Ikebe S-i et al. Quantitative determination of deleted mitochondrial DNA relative to normal DNA in parkinsonian striatum by a kinetic PCR. Biochem Biophys Res Commun 199o; 172: 483–489.

    Google Scholar 

  34. Zhang C, Peters LE, Linnane AW et al. Comparison of different quantitative PCR procedures in the analysis of the 4977-bp deletion in human mitochondrial DNA. Biochem Biophys Res Commun 1996; 223: 450–455.

    PubMed  CAS  Google Scholar 

  35. Hamblet NS, Castora FJ. Mitochondrial DNA deletion analysis: A comparison of PCR quantitative methods. Biochem Biophys Res Commun 1995; 207: 839–847.

    PubMed  CAS  Google Scholar 

  36. Zhang C, Liu VWS, Addessi CL et al. Differential occurrence of mutations in mitochondrial DNA of human skeletal muscle during aging. Hum Mutation 1998; in press.

    Google Scholar 

  37. Pallotti F, Chen X, Bonilla E et al. Evidence that specific mtDNA point mutations may not accumulate in skeletal muscle during normal human aging. Am J Hum Genet 1996; 59: 591–602.

    PubMed  CAS  Google Scholar 

  38. Sato W, Tanaka M, Ohno K et al. Multiple populations of deleted mitochondrial DNA detected by a novel gene amplification method. Biochem Biophys Res Commun 1989; 162: 664–672.

    PubMed  CAS  Google Scholar 

  39. Van Tuyle GC, Gudikote JP, Hurt VR et al. Multiple, large deletions in rat mitochondrial DNA: Evidence for a major hot spot. Mutation Res 1996; 349: 95–107.

    PubMed  CAS  Google Scholar 

  40. Hattori K, Tanaka M, Sugiyama S et al. Age-dependent increase in deleted mitochondrial DNA in human heart: Possible contributory factor to presbycardia. Am Heart J 1991; 121: 1735–1742.

    PubMed  CAS  Google Scholar 

  41. Yen T-C, Pang C-Y, Hsieh R-H et al. Age-dependent 6 kb deletion in human liver mitochondrial DNA. Biochem Int 1992; 26: 457–468.

    PubMed  CAS  Google Scholar 

  42. Katsumata K, Hayakawa M, Tanaka M et al. Fragmentation of human heart mitochondrial DNA associated with premature aging. Biochem Biophys Res Commun 1994; 202: 102–110.

    PubMed  CAS  Google Scholar 

  43. Hayakawa M, Katsumata K, Yoneda M et al. Mitochondrial DNA minicircles, lacking replication origins, exist in the cardiac muscle of a young normal subject. Biochem Biophys Res Commun 1995; 215: 952–960.

    PubMed  CAS  Google Scholar 

  44. Hayakawa M, Katsumata K, Yoneda M et al. Age-related extensive fragmentation of mitochondrial DNA into minicircles. Biochem Biophys Res Commun 1996; 226: 369–377.

    PubMed  CAS  Google Scholar 

  45. Ballinger SW, Shoffner JM, Gebhart S et al. Mitochondrial diabetes revisited. Nature Genet 1994; 7: 458–459.

    PubMed  CAS  Google Scholar 

  46. Pouton J, Holt IJ. Mitochondrial DNA: Does more lead to less? Nature Genet 1994; 8:313–315.

    Google Scholar 

  47. Cheng S, Higuchi R, Stoneking M. Complete mitochondrial genome amplification. Nature Genet 1994; 7: 350–351.

    PubMed  CAS  Google Scholar 

  48. Melov S, Shoffner JM, Kaufman A et al. Marked increase in the number and variety of mitochondrial DNA rearrangements in aging human skeletal muscle. Nucleic Acids Res 1995; 23: 4122–4126.

    PubMed  CAS  Google Scholar 

  49. Li Y-Y, Hengstenberg C, Maisch B. Whole mitochondrial genome amplification reveals basal level multiple deletions in mtDNA of patients with dilated cardiomyopathy. Biochem Biophys Res Commun 1995; 210: 211–218.

    PubMed  CAS  Google Scholar 

  50. Reynier P, Malthiery Y. Accumulation of deletions in mtDNA during tissue aging: Analysis by long PCR. Biochem Biophys Res Commun 1995; 217: 59–67.

    PubMed  CAS  Google Scholar 

  51. Kovalenko SA, Kopsidas G, Kelso JM et al. Deltoid human muscle mtDNA is extensively rearranged in old age subjects. Biochem Biophys Res Commun 1997; 232: 147–152.

    PubMed  CAS  Google Scholar 

  52. Barnes WM. PCR amplification of up to 35-kb DNA with high fidelity and high yield from A bacteriophage templates. Proc Natl Acad Sci USA 1994; 91: 2216–2220.

    PubMed  CAS  Google Scholar 

  53. Cheng S, Fockler C, Barnes WM et al. Effective amplification of long targets from cloned inserts and human genomic DNA. Proc Natl Acad Sci USA 1994; 91: 5695–5699.

    PubMed  CAS  Google Scholar 

  54. Zhang C, Baumer A, Mackay IR et al. Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult human with chronic fatigue syndrome. Hum Mol Genet 1995; 4: 751–754.

    PubMed  CAS  Google Scholar 

  55. Zhang C, Bills M, Quigley A et al. Varied prevalence of age-associated mitochondrial DNA deletions in different species and tissues: A comparison between human and rat. Biochem Biophys Res Commun 1997; 230: 630–635.

    PubMed  CAS  Google Scholar 

  56. Linnane AW, Baumer A, Boubolas A et al. Mitochondrial mutations and the aging process. In: Papa S, Azzi A, Trager JM, eds. Adenine Nucleotides in Cellular Energy Transfer and Signal Transduction. Basel: Birkhauser Verlag, 1992: 137–149.

    Google Scholar 

  57. Zhang C, Linnane AW, Nagley P. Occurrence of a particular base substitution (3243 A to G) in mitochondrial DNA of tissues of aging humans. Biochem Biophys Res Commun 1993; 195: 1104–1110.

    PubMed  CAS  Google Scholar 

  58. Münscher C, Rieger T, Müller-Höcker J et al. The point mutation of mitochondrial DNA characteristic for MERRF disease is found also in healthy people of different ages. FEBS Lett 1993; 317: 27–30.

    PubMed  Google Scholar 

  59. Münscher C, Müller-Höcker J, Kadenbach B. Human aging is associated with various point mutations in tRNA genes of mitochondrial DNA. Biol Chem HoppeSeyler 1993; 374: 1099–1104.

    Google Scholar 

  60. Rieger T, Münscher C, Seibel P et al. Detection of small amounts of mutated mitochondrial DNA by allele-specific PCR (AS-PCR). Methods Mol Cell Biol 1993; 4: 121–127.

    CAS  Google Scholar 

  61. Kadenbach B, Münscher C, Frank V et al. Human aging is associated with stochastic somatic mutations of mitochondrial DNA. Mutation Res 1995; 338: 161–172.

    PubMed  CAS  Google Scholar 

  62. Liu VWS, Zhang C, Linnane AW et al. Quantitative allele-specific PCR: Demonstration of age-associated accumulation in human tissues of the A-G mutation at nucleotide 3243 in mitochondrial DNA. Hum Mutation 1997; 9: 265–271.

    CAS  Google Scholar 

  63. Liu VWS, Zhang C, NagleyP. Mutations in mitochondrial DNA accumulate differentially in three different human tissues during aging. Nucleic Acids Res 1998; 26: 1268–1275.

    PubMed  CAS  Google Scholar 

  64. Liu VWS, Zhang C, Pang C-Y et al. Independent occurrence of somatic mutations in mitochondrial DNA of human skin from subjects of various ages. Hum. Mutation 1997; in press.

    Google Scholar 

  65. Lee H-C, Pang C-Y, Hsu H-S et al. Aging-associated tandem duplications in the D-loop of mitochondrial DNA of human muscle. FEBS Lett 1994; 354: 79–83.

    PubMed  CAS  Google Scholar 

  66. Yang J-H, Lee H-C, Wei Y-H. Photoaging-associated mitochondrial DNA length mutations in human skin. Arch Dermatol Res 1995; 287: 641–648.

    PubMed  CAS  Google Scholar 

  67. Wei Y-H, Pang C-Y, You B-J et al. Tandem duplications and large-scale deletions of mitochondrial DNA are early molecular events of human aging process. Ann New York Acad Sci 1996; 786: 82–101.

    CAS  Google Scholar 

  68. Nagley P, Zhang C, Martinus RD et al. Mitochondrial DNA mutation and human aging: Molecular biology, bioenergetics, and redox therapy. In: DiMauro S, Wallace DC, eds. Mitochondrial DNA in Human Pathology. New York: Raven Press, 1993: 137–157.

    Google Scholar 

  69. Müller-Höcker J. Cytochrome-c-oxidase deficient cardiomyocytes in the human heart-An age-related phenomenon: A histochemical ultracytochemical study. Am J Pathol 1989; 134: 1167–1173.

    PubMed  Google Scholar 

  70. Nagley P, Mackay IR, Baumer A et al. Mitochondrial DNA mutations associated with aging and degenerative disease. Ann NY Acad Sci 1992; 673: 92–102.

    PubMed  CAS  Google Scholar 

  71. Müller-Höcker J. Cytochrome c oxidase deficient fibres in the limb muscle and diaphragm of man without muscular disease: An age-related alteration. J Neurol Sci 1990; 100: 4–21.

    Google Scholar 

  72. Müller-Höcker J, Seibel P, Schneiderbanger K et al. Different in situ hybridization patterns of mitochondrial DNA in cytochrome c oxidase-deficient extraocular muscle fibres in the elderly. Virchows Archiv A Pathol Anat 1993; 42: 27–15.

    Google Scholar 

  73. Oldfors A, Larsson N-G, Holme E et al. Mitochondrial DNA deletions and cytochrome c oxidase deficiency in muscle fibres. J Neurol Sci 1992; 110: 169–177.

    PubMed  CAS  Google Scholar 

  74. Petruzzella V, Moraes CT, Sano MC et al. Extremely high levels of mutant mtDNAs co-localize with cytochrome c oxidase-negative ragged-red fibers in patients harboring a point mutation at nt 3243. Hum Mol Genet 1994; 3: 449–454.

    PubMed  CAS  Google Scholar 

  75. Sciacco M, Bonilla E, Schon EA et al. Distribution of wild-type and common deletion forms of mtDNA in normal and respiration-deficient muscle fibers from patients with mitochondrial myopathy. Hum Mol Genet 1994; 3: 13–19.

    PubMed  CAS  Google Scholar 

  76. Zhang C, Liu VWS, Nagley P. Gross mosaic pattern of mitochondrial DNA deletions in skeletal muscle tissues of an individual adult human subject. Biochem Biophys Res Commun 1997; 233: 56–60.

    PubMed  CAS  Google Scholar 

  77. Moraes CT, Schon EA. Detection and analysis of mitochondrial DNA and RNA in muscle by in situ hybridization and single-fiber PCR. Methods Enzymol 1996; 264: 522–540.

    PubMed  CAS  Google Scholar 

  78. Kovalenko SA, Harms PJ, Tanaka M et al. Method for in situ investigation of mitochondrial DNA deletions. Hum Mutation 1997; 10: 489–495.

    CAS  Google Scholar 

  79. Dawid IB, Blackler AW. Maternal and cytoplasmic inheritance of mitochondrial DNA in Xenopus. Dey Biol 1972; 29: 152–161.

    CAS  Google Scholar 

  80. Hauswirth WW, Laipis PJ. Transmission genetics of mammalian mitochondria: A molecular model and experimental evidence. In: Quagliariello E, Slater EC, Palmieri F et al. eds. Achievements and Perspectives of Mitochondrial Research, Vol. II. Amsterdam: Elsevier, 1985: 49–59.

    Google Scholar 

  81. Koehler CM, Lindberg GL, Brown DR et al. Replacement of bovine mitochondrial DNA by a sequence variant within one generation. Genetics 1991; 129: 247–255.

    PubMed  CAS  Google Scholar 

  82. Bolhuis PA, Bleeker-Wagemakers EM, Ponne NJ et al. Rapid shift in genotype of human mitochondrial DNA in a family with Leber’s hereditary optic neuropathy. Biochem Biophys Res Commun 1990; 170: 994–997.

    PubMed  CAS  Google Scholar 

  83. Tulinius MH, Houshmand M, Larsson N-G et al. De novo mutation in the mito-chondrial ATP synthase subunit 6 gene (T8993G) with rapid segregation resulting in Leigh syndrome in the offspring. Hum Genet 1995; 96: 290–294.

    PubMed  CAS  Google Scholar 

  84. Parsons TJ, Muniec DS, Sullivan K et al. A high observed substitution rate in the human mitochondrial DNA control region. Nature Genet 1997; 15: 363–368.

    PubMed  CAS  Google Scholar 

  85. Howell N, Halvorson S, Kubacka I et al. Mitochondrial gene segregation in mammals: Is the bottleneck always narrow? Hum Genet 1992; 90: 117–120.

    PubMed  CAS  Google Scholar 

  86. Bendall KE, Sykes BC. Length heteroplasmy in the first hypervariable segment of the human mtDNA control region. Am J Hum Genet 1995; 57: 248–256.

    PubMed  CAS  Google Scholar 

  87. Blok RB, Gook DA, Thorburn DR et al. Skewed segregation of the mtDNA nt8993 (T-9G) mutation in human oocytes. Am J Hum Genet 1997; 60: 1495–1501.

    PubMed  CAS  Google Scholar 

  88. Jenuth JP, Peterson AC, Fu K et al. Random genetic drift in the female germline explains the rapid segregation of mammalian mitochondrial DNA. Nature Genet 1996; 14: 146–151.

    PubMed  CAS  Google Scholar 

  89. Chen X, Prosser R, Simonetti S et al. Rearranged mitochondrial genomes are present in human oocytes. Am J Hum Genet 1995; 57: 239–247.

    PubMed  CAS  Google Scholar 

  90. Chen X, Simonetti S, DiMauro S et al. Accumulation of mitochondrial DNA deletions in organisms with various lifespans. Bull Mol Biol Med 1993; 18: 57–66.

    CAS  Google Scholar 

  91. Gadaleta MN, Rainaldi G, Lezza AMS et al. Mitochondrial DNA copy number and mitochondrial DNA deletion in adult and senescent rats. Mutation Res 1992; 275: 181–193.

    PubMed  CAS  Google Scholar 

  92. Edris W, Burgett B, Stine OC et al. Detection and quantitation by competitive PCR of an age-associated increase in a 4.8-kb deletion in rat mitochondrial DNA. Mutation Res 1994; 316: 69–78.

    PubMed  CAS  Google Scholar 

  93. Nelson I, Gerasimov S, Marsac C et al. Sequence analysis of a deleted mitochondrial DNA molecule in heteroplasmic mice. Mammalian Genome 1993; 4: 680–683.

    PubMed  CAS  Google Scholar 

  94. Takai D, Inoue K, Shisa H et al. Age-associated changes of mitochondrial translation and respiratory function in mouse brain. Biochem Biophys Res Commun 1995; 217: 668–674.

    PubMed  CAS  Google Scholar 

  95. Brossas J-Y, Barreau E, Courtois Y et al. Multiple deletions in mitochondrial DNA are present in senescent mouse brain. Biochem Biophys Res Commun 1994; 202: 654–659.

    PubMed  CAS  Google Scholar 

  96. Chung SS, Weindruch R, Schwarze SR et al. Multiple age-associated mitochondrial DNA deletions in skeletal muscle of mice. Aging Clin Exp Res 1994; 6: 193–200.

    CAS  Google Scholar 

  97. Tanhauser SM, Laipis PJ. Multiple deletions are detectable in mitochondrial DNA of aging mice. J Biol Chem 1995; 270: 24769–24775.

    PubMed  CAS  Google Scholar 

  98. Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ. Presence of a mitochondrial DNA deletion in fetal and adult bovine cardiac tissue. Biochem Mol Biol Int 1994; 33: 817–825.

    PubMed  CAS  Google Scholar 

  99. Lee CM, Chung SS, Kaczkowski JM et al. Multiple mitochondrial DNA deletions associated with age in skeletal muscle of rhesus monkeys. J Gerontol 1993; 48:B2o1B2o5.

    Google Scholar 

  100. Lee CM, Eimon P, Weindruch R et al. Direct repeat sequences are not required at the breakpoints of age-associated mitochondrial DNA deletions in rhesus monkeys. Mech Aging Dev 1994; 75: 69–79.

    PubMed  CAS  Google Scholar 

  101. Schwarze SR, Lee CM, Chung SS et al. High levels of mitochondrial DNA deletions in skeletal muscle of old rhesus monkeys. Mech Aging Devel 1995; 8391–101.

    Google Scholar 

  102. Wood WB, Johnson TE. Stopping the clock. Curr Biol 1994; 4151–153.

    Google Scholar 

  103. Melov S, Hertz GZ, Stormo GD et al. Detection of deletions in the mitochondrial genome of Caenorhabditis elegans. Nucleic Acids Res 1994; 22: 1075–1078.

    PubMed  CAS  Google Scholar 

  104. Melov S, Lithgow GJ, Fischer DR et al. Increased frequency of deletions in the mitochondrial genome with age of Caenorhabditis elegans. Nucleic Acids Res 1995; 23: 1419–1425.

    PubMed  CAS  Google Scholar 

  105. Trounce I, Byrne E, Marzuki S. Decline in skeletal muscle mitochondrial respiratory chain function: Possible factor in aging. Lancet 1989; 1: 637–639.

    CAS  Google Scholar 

  106. Yen T-C, Chen Y-S, King K-L et al. Liver mitochondrial respiratory functions decline with age. Biochem Biophys Res Commun 1989; 165: 994–1003.

    Google Scholar 

  107. Hayakawa M, Torii K, Sugiyama S et al. Age-associated accumulation of 8hydroxydeoxyguanosine in mitochondrial DNA of human diaphragm. Biochem Biophys Res Commun 1991; 179: 023–1029.

    Google Scholar 

  108. Mecocci P, MacGarvey U, Kaufman AE et al. Oxidative damage to mitochondrial DNA shows marked age-dependent increase in human brain. Ann Neurol 1993; 34: 609–616.

    PubMed  CAS  Google Scholar 

  109. Pinz KG, Shibutani S, Bogenhagen DF. Action of mitochondrial DNA polymerase y at sites of base loss or oxidative damage. J Biol Chem 1995; 270: 9202–9206.

    PubMed  CAS  Google Scholar 

  110. Cortopassi G, Wang E. Modelling the effects of age-related mtDNA mutation accumulation; Complex I deficiency, superoxide and cell death. Biochim Biophys Acta 1995; 1271: 171–176.

    Google Scholar 

  111. Wolvetang EJ, Johnson KL, Krauer K et al. Mitochondrial respiratory chain inhibitors induce apoptosis. FEBS Lett 1994; 339: 40–44.

    PubMed  CAS  Google Scholar 

  112. Petit PX, Susin S-A, Zamzami N et al. Mitochondria and programmed cell death: Back to the future. FEBS Lett 1996; 396: 7–13.

    PubMed  CAS  Google Scholar 

  113. Skulachev VP. Why are mitochondria involved in apoptosis? FEBS Lett 1996; 397: 7–1o.

    PubMed  CAS  Google Scholar 

  114. Shoffner JM, Lott MT, Voljavec AS et al. Spontaneous Kearns-Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion: A slip-replication model and metabolic therapy. Proc Nall Acad Sci USA 1989; 86: 7952–7956.

    CAS  Google Scholar 

  115. Esser K, Martin GM (eds) Molecular aspects of aging. Chichester: John Wiley & Sons, 1995.

    Google Scholar 

  116. Yoneda M, Chomyn A, Martinuzzi A et al. Marked replicative advantage of human mtDNA carrying a point mutation that causes the MELAS encephalomyopathy. Proc Natl Acad Sci USA 1992; 89: 11164–11168.

    PubMed  CAS  Google Scholar 

  117. Dunbar D, Moonie P, Jacobs H et al. Different cellular backgrounds confer a marked advantage to either mutant or wild-type mitochondrial genomes. Proc Natl Acad Sci USA 1995; 92: 6562–6566.

    PubMed  CAS  Google Scholar 

  118. de Grey ADNJ. A proposed refinement of the mitochondrial free radical theory of aging. BioEssays 1997; 19: 161–166.

    PubMed  Google Scholar 

Download references

Authors
  1. Phillip Nagley
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunfang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. The Division of Experimental Therapeutics and Radiation Oncology, Johns Hopkins Oncology Center and Department of Environmental Health, Johns Hopkins School of Public Health, 600 N. Wolfe Street, Room 2-121, 21287, Baltimore, Maryland, USA

    Keshav K. Singh Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Nagley, P., Zhang, C. (1998). Mitochondrial DNA Mutations in Aging. In: Singh, K.K. (eds) Mitochondrial DNA Mutations in Aging, Disease and Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-12509-0_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-12509-0_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-12511-3

  • Online ISBN: 978-3-662-12509-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation