Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain
A major theory of aging is that oxidative damage may accumulate in DNA and contribute to physiological changes associated with aging. We examined age‐related accumulation of oxidative damage to both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in human brain tissue. We measured the oxidized nucl...
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| Veröffentlicht in: | Annals of neurology 1993-10, Vol.34 (4), p.609-616 |
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| container_title | Annals of neurology |
| container_volume | 34 |
| creator | Mecocci, Patrizia MacGarvey, Usha Kaufman, Allan E. Koontz, Deborah Shoffner, John M. Wallace, Douglas C. Beal, M. Flint |
| description | A major theory of aging is that oxidative damage may accumulate in DNA and contribute to physiological changes associated with aging. We examined age‐related accumulation of oxidative damage to both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in human brain tissue. We measured the oxidized nucleoside, 8‐hydroxy‐2′‐deoxyguanosine (OH8dG), in DNA isolated from 3 regions of cerebral cortex and cerebellum from 10 normal humans aged 42 to 97 years. The amount of OH8dG, expressed as a ratio of the amount of deoxyguanosine (dG) or as fmol/μg of DNA, increased progressively with normal aging in both nDNA and mtDNA; however, the rate of increase with age was much greater in mtDNA. There was a significant 10‐fold increase in the amount of OH8dG in mtDNA as compared with nDNA in the entire group of samples, and a 15‐fold significant increase in patients older than 70 years. These results show for the first time that there is a progressive age‐related accumulation in oxidative damage to DNA in human brain, and that the mtDNA is preferentially affected. It is possible that such damage may contribute to age‐dependent increases in incidence of neurodegenerative diseases. |
| doi_str_mv | 10.1002/ana.410340416 |
| format | Article |
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Flint</creator><creatorcontrib>Mecocci, Patrizia ; MacGarvey, Usha ; Kaufman, Allan E. ; Koontz, Deborah ; Shoffner, John M. ; Wallace, Douglas C. ; Beal, M. Flint</creatorcontrib><description>A major theory of aging is that oxidative damage may accumulate in DNA and contribute to physiological changes associated with aging. We examined age‐related accumulation of oxidative damage to both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in human brain tissue. We measured the oxidized nucleoside, 8‐hydroxy‐2′‐deoxyguanosine (OH8dG), in DNA isolated from 3 regions of cerebral cortex and cerebellum from 10 normal humans aged 42 to 97 years. The amount of OH8dG, expressed as a ratio of the amount of deoxyguanosine (dG) or as fmol/μg of DNA, increased progressively with normal aging in both nDNA and mtDNA; however, the rate of increase with age was much greater in mtDNA. There was a significant 10‐fold increase in the amount of OH8dG in mtDNA as compared with nDNA in the entire group of samples, and a 15‐fold significant increase in patients older than 70 years. These results show for the first time that there is a progressive age‐related accumulation in oxidative damage to DNA in human brain, and that the mtDNA is preferentially affected. It is possible that such damage may contribute to age‐dependent increases in incidence of neurodegenerative diseases.</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.410340416</identifier><identifier>PMID: 8215249</identifier><identifier>CODEN: ANNED3</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Aging - metabolism ; Biological and medical sciences ; Brain - metabolism ; Cell Nucleus - metabolism ; Deoxyguanosine - analogs & derivatives ; Deoxyguanosine - metabolism ; Development. Metamorphosis. Moult. Ageing ; DNA - metabolism ; DNA, Mitochondrial - metabolism ; Female ; Fundamental and applied biological sciences. 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Flint</creatorcontrib><title>Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>A major theory of aging is that oxidative damage may accumulate in DNA and contribute to physiological changes associated with aging. We examined age‐related accumulation of oxidative damage to both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in human brain tissue. We measured the oxidized nucleoside, 8‐hydroxy‐2′‐deoxyguanosine (OH8dG), in DNA isolated from 3 regions of cerebral cortex and cerebellum from 10 normal humans aged 42 to 97 years. The amount of OH8dG, expressed as a ratio of the amount of deoxyguanosine (dG) or as fmol/μg of DNA, increased progressively with normal aging in both nDNA and mtDNA; however, the rate of increase with age was much greater in mtDNA. There was a significant 10‐fold increase in the amount of OH8dG in mtDNA as compared with nDNA in the entire group of samples, and a 15‐fold significant increase in patients older than 70 years. These results show for the first time that there is a progressive age‐related accumulation in oxidative damage to DNA in human brain, and that the mtDNA is preferentially affected. It is possible that such damage may contribute to age‐dependent increases in incidence of neurodegenerative diseases.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aging - metabolism</subject><subject>Biological and medical sciences</subject><subject>Brain - metabolism</subject><subject>Cell Nucleus - metabolism</subject><subject>Deoxyguanosine - analogs & derivatives</subject><subject>Deoxyguanosine - metabolism</subject><subject>Development. Metamorphosis. Moult. Ageing</subject><subject>DNA - metabolism</subject><subject>DNA, Mitochondrial - metabolism</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Oxidation-Reduction</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtvEzEUhS0EKmlhyRLJC8Ruij322DPLqIUArVIp4iFW1h37mhjmEexJH_8eVxlFrFjZ0vnu8bnHhLzi7JwzVr6DAc4lZ0IyydUTsuCV4EVdyuYpWTChZFFxIZ-T05R-McYaxdkJOalLXmVkQX7c3AcHU7hF6qCHn0inkfZhGu12HFwM0NHL9ZKm7XiXaA_xNzqaqcLhDgeHw0TDYCNCwpRvdLvvYaBthDC8IM88dAlfzucZ-frh_ZeLj8X1zerTxfK6sFI1qnC8cpUt69Zz2wqJrGy55E3tfSM9uMazHFWiVYBVKcDrWjpVAeMaVCUVF2fk7cF3F8c_e0yT6UOy2HUw4LhPRqvsIJXIYHEAbRxTiujNLoa80oPhzDxWaXKV5lhl5l_Pxvu2R3ek5-6y_mbWIVnofITBhnTERC201o_59AG7Cx0-_P9Ns1wv_w0wBw5pwvvjZP4Eo7TQlfm-XpnN6tvm85W8MhvxF77-msM</recordid><startdate>199310</startdate><enddate>199310</enddate><creator>Mecocci, Patrizia</creator><creator>MacGarvey, Usha</creator><creator>Kaufman, Allan E.</creator><creator>Koontz, Deborah</creator><creator>Shoffner, John M.</creator><creator>Wallace, Douglas C.</creator><creator>Beal, M. 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The amount of OH8dG, expressed as a ratio of the amount of deoxyguanosine (dG) or as fmol/μg of DNA, increased progressively with normal aging in both nDNA and mtDNA; however, the rate of increase with age was much greater in mtDNA. There was a significant 10‐fold increase in the amount of OH8dG in mtDNA as compared with nDNA in the entire group of samples, and a 15‐fold significant increase in patients older than 70 years. These results show for the first time that there is a progressive age‐related accumulation in oxidative damage to DNA in human brain, and that the mtDNA is preferentially affected. It is possible that such damage may contribute to age‐dependent increases in incidence of neurodegenerative diseases.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>8215249</pmid><doi>10.1002/ana.410340416</doi><tpages>8</tpages></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Aging - metabolism Biological and medical sciences Brain - metabolism Cell Nucleus - metabolism Deoxyguanosine - analogs & derivatives Deoxyguanosine - metabolism Development. Metamorphosis. Moult. Ageing DNA - metabolism DNA, Mitochondrial - metabolism Female Fundamental and applied biological sciences. Psychology Humans Male Middle Aged Oxidation-Reduction Vertebrates: anatomy and physiology, studies on body, several organs or systems |
| title | Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain |
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