Abstract
Mitochondrial DNA (mtDNA) mutations have recently been proposed as important contributors to ageing and degenerative diseases. In this study, we applied the polymerase chain reaction technique to detect 4.977 bp-deleted mtDNA, the most common and abundant deletion of mtDNA, in normal human skin. None of the skin specimens from patients less than 60 years of age were found to bear this type of mtDNA deletion. The incidence of the 4977-bp-deleted mtDNA increased with advancing age. The incidence of the deletion was 20%, 46.7% and 83.4% for patients of the age groups of 61–70, 71–80, and 81–90 years, respectively. Moreover, the incidence of 4977-bp-deleted mtDNA was significantly higher in exposed skin than that in non-exposed skin. We suggest that mtDNA mutations are molecular events associated with the human skin ageing process.
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Balin AK, Allen RG (1986) Mechanisms of biologic aging. Dermatol Clin 4: 347–358
Harman D (1992) Free radical theory of aging. Mutat Res 275: 257–266
Freeman BA, Crapo JD (1982) Free radicals and tissue injury. Lab Invest 47: 412–426
Cerimele D, Celleno JD, Serri F (1990) Physiologic changes in ageing skin. Br J Dermatol 122 [Suppl 35]: 13–20
Rogers GS, Gilchrest BA (1990) The senile epidermis: environmental influences on skin ageing and cutaneous carcinogenesis. Br J Dermatol 122 [Suppl 35]: 55–60
Norins AL (1962) Free radical formation in the skin following exposure to ultraviolet light. J Invest Dermatol 39: 445–448
Gilchrest BA, Yaar M (1992) Ageing and photoageing of the skin: observations at the cellular and molecular level. Br J Dermatol 127 [Suppl 41]: 25–30
Uitto J, Fazio MJ, Olsen DR (1989) Molecular mechanisms of cutaneous aging: age-associated connective tissue alterations in the dermis. J Am Acad Dermatol 21: 614–622
Anderson S, Bankier AT, Barrel BG, de Bruijn MHL, Coulson AR, Drouin J, et al (1981) Sequence and organization of the human mitochondrial genome. Nature 290: 457–465
Poulton J (1992) Mitochondrial DNA and genetic disease. Bioessays 14: 763–768
Wallace DC (1992) Diseases of the mitochondrial DNA. Annu Rev Biochem 61: 1175–1212
Clayton DA, Doda JN, Friedberg EC (1974) The absence of a pyrimidine dimer repair mechanism in mammalian mitochondria. Proc Natl Acad Sci USA 71: 2777–2781
Tomkinson AE, Bonk RT, Linn S (1990) Mammalian mitochondrial endonuclease activities specific for ultraviolet-irradiated DNA. Nucleic Acids Res 18: 929–935
Linnane AW, Marzuki S, Ozawa T, Tanaka M (1989) Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet I: 642–645
Yen TC, Chen YS, King KL, Yeh SH, Wei YH (1989) Liver mitochondrial respiratory functions decline with age. Biochem Biophys Res Commun 65: 994–1003
Trounce I, Byrne E, Marzuki S (1989) Decline in skeletal muscle mitochondrial respiratory chain function: possible factor in ageing. Lancet I: 637–639
Ikebe S, Tanaka M, Ohno K, Sato W, Hattori K, Kondo T, et al (1990) Increase of deleted mitochondrial DNA in the striatum in Parkinson's disease and senescence. Biochem Biophys Res Commun 170: 1044–1048
Hattori K, Tanaka M, Sugiyama S, Obayashi T, Ito T, et al (1991) Age-dependent increase in deleted mitochondrial DNA in the human heart: possible contributory factor to presbycardia. Am Heart J 121: 1735–1742
Yen TC, Su JH, King KL, Wei YH (1991) Ageing-associated 5kb deletion in human liver mitochondrial DNA. Biochem Biophys Res Commun 178: 124–131
Wei YH (1992) Mitochondrial DNA alterations as ageing-associated molecular events. Mutat Res 275: 145–155
Cortopassi GA, Shibata D, Soong NW, Arnheim N (1992) A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proc Natl Acad Sci USA 89: 7370–7374
Palva TK, Palva ET (1985) Rapid isolation of animal mitochondrial DNA by alkaline extraction. FEBS Lett 192: 267–270
Tanaka M, Ozawa T (1992) Analysis of mitochondrial DNA mutations. In: Longstaff A, Revest P (eds) Methods in molecular biology. Humana, Totowa, pp 1–28
Gilchrest BA (1989) Skin aging and photoaging: an overview. J Am Acad Dermatol 21: 610–613
Serri F, Borrelo S, Seccia A (1980) Superoxide dismutase content in human epidermis and squamous cell carcinoma. Arch Dermatol Res 267: 83–86
Celleno L, Serri F (1987) The pathogenetic role of free radicals in cutaneous aging and skin cancer. G Ital Chir Dermatol 2: 264–266
Fuchs J, Huflejt ME, Laurie MS, Rothfuss LM, David AB, Wilson DS, et al (1989) Impairment of enzymic and nonenzymic antioxidants in skin by UVB irradiation. J Invest Dermatol 93: 769–773
Shindo T, Witte E, Packer L (1993) Antioxidant defense mechanisms in murine epidermis and dermis and their responses to ultraviolet light. J Invest Dermatol 100: 260–265
Linnane AW, Baumer A, Maxwell RJ, Preston H, Zhang C, Marzuki S (1990) Mitochondrial gene mutation: the ageing process and degenerative diseases. Biochem Int 22: 1067–1076
Vosberg H (1989) The polymerase chain reaction: an improved method for the analysis of nucleic acids. Hum Genet 83: 1–15
Paludan K, Thestrup-Pederson K (1993) The polymerase chain reaction and dermatology. Acta Derm Venereol (Stockh) 73: 1–6
Randall T (1991) Mitochondrial DNA: a new frontier in acquired and inborn gene defects. J Am Med Assoc 266: 1739–1740
Linnane AW, Zhang C, Baumer A, Nagley P (1992) Mitochondrial DNA mutation and the ageing process: bioenergy and pharmacological intervention. Mutat Res 275: 195–208
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Yang, J.H., Lee, H.C., Lin, K.J. et al. A specific 4977-bp deletion of mitochondrial DNA in human ageing skin. Arch Dermatol Res 286, 386–390 (1994). https://doi.org/10.1007/BF00371798
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DOI: https://doi.org/10.1007/BF00371798