Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain
Abstract
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/micrograms 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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Oxidation of DNA and RNA produced by reactive oxygen species occurs in Alzheimer's disease.
“Oxidation of DNA and RNA produced by ROS also occurs in AD [50,51,52,53].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [50]
There is a progressive age-related accumulation of oxidative damage to DNA in the human brain, and mitochondrial DNA is preferentially affected; increased 8-OHdG in mtDNA and nuclear DNA is demonstrated in the aging human brain and in Alzheimer's disease.
“It is demonstrated that there is a progressive age-related accumulation of oxidative damage to DNA in the human brain and that mtDNA is preferentially affected. The increased amount of 8-OHdG in mtDNA and nuclear DNA is demonstrated in the aging human brain and in AD [50,51,64].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [50]
Cites
Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., Deng, H.-X., et al. (1993) · Nature · doi:10.1038/362059a0 · Cited by 7,062 · see citing works
Rapid evolution of animal mitochondrial DNA
Brown, W. M., George, M., & Wilson, A. C. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.4.1967 · Cited by 3,439 · see citing works
Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG
Shibutani, S., Takeshita, M., & Grollman, A. P. (1991) · Nature · doi:10.1038/349431a0 · Cited by 2,224 · see citing works
8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G-T and A-C substitutions.
Cheng, K. C., Cahill, D. S., Kasai, H., Nishimura, S., & Loeb, L. A. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48474-8 · Cited by 1,844 · see citing works
Normal oxidative damage to mitochondrial and nuclear DNA is extensive.
Richter, C., Park, J. W., & Ames, B. N. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.17.6465 · Cited by 1,730 · see citing works
Evans, D. A. (1989) · JAMA · doi:10.1001/jama.262.18.2551 · Cited by 1,627 · see citing works
Shoffner, J. M., Lott, M. T., Lezza, A. M. S., Seibel, P., Ballinger, S. W., & Wallace, D. C. (1990) · Cell · doi:10.1016/0092-8674(90)90059-n · Cited by 1,468 · see citing works
Mitochondrial Genetics: A Paradigm for Aging and Degenerative Diseases?
Wallace, D. C. (1992) · Science · doi:10.1126/science.1533953 · Cited by 1,256 · see citing works
Evans, D. A. (1989) · JAMA · doi:10.1001/jama.1989.03430180093036 · Cited by 1,226 · see citing works
MITOCHONDRIAL DNA MUTATIONS AS AN IMPORTANT CONTRIBUTOR TO AGEING AND DEGENERATIVE DISEASES
Linnane, A. W., Ozawa, T., Marzuki, S., & Tanaka, M. (1989) · The Lancet · doi:10.1016/s0140-6736(89)92145-4 · Cited by 1,192 · see citing works
Oxidative damage to DNA during aging: 8-hydroxy-2'-deoxyguanosine in rat organ DNA and urine.
Fraga, C. G., Shigenaga, M. K., Park, J. W., Degan, P., & Ames, B. N. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.12.4533 · Cited by 1,106 · see citing works
Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents
Kasai, H., & Nishimura, S. (1984) · Nucleic Acids Research · doi:10.1093/nar/12.4.2137 · Cited by 948 · see citing works
Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age
Corral-Debrinski, M., Horton, T., Lott, M. T., Shoffner, J. M., Flint Beal, M., & Wallace, D. C. (1992) · Nature Genetics · doi:10.1038/ng1292-324 · Cited by 890 · see citing works
Self-citationKuchino, Y., Mori, F., Kasai, H., Inoue, H., Iwai, S., Miura, K., Ohtsuka, E., & Nishimura, S. (1987) · Nature · doi:10.1038/327077a0 · Cited by 770 · see citing works
Decline in skeletal muscle mitochondrial respiratory chain function: possible factor in ageing
Trounce, I., Byrne, E., & Marzuki, S. (1989) · The Lancet · doi:10.1016/s0140-6736(89)92143-0 · Cited by 730 · see citing works
Endogenous mutagens and the causes of aging and cancer
Ames, B. N., & Gold, L. S. (1991) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(91)90157-j · Cited by 716 · see citing works
Wood, M. L., Dizdaroğlu, M., Gajewski, E., & Essigmann, J. M. (1990) · Biochemistry · doi:10.1021/bi00482a011 · Cited by 684 · see citing works
A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues.
Cortopassi, G. A., Shibata, D. K., Soong, N.-W., & Arnheim, N. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.16.7370 · Cited by 639 · see citing works
Moraes, C. T., Shanske, S., Tritschler, H., Aprille, J. R., Andreetta, F., Bonilla, E., Schon, E. A., & DiMauro, S. (1991) · PubMed · Cited by 583 · see citing works
The Absence of a Pyrimidine Dimer Repair Mechanism in Mammalian Mitochondria
Clayton, D. A., Doda, J. N., & Friedberg, E. C. (1974) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.71.7.2777 · Cited by 531 · see citing works
Chemical determination of free radical-induced damage to DNA
Dizdaroğlu, M. (1991) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(91)90080-m · Cited by 526 · see citing works
Mitochondrial DNA Variants Observed in Alzheimer Disease and Parkinson Disease Patients
Shoffner, J. M., Brown, M. D., Torroni, A., Lott, M. T., Cabell, M. F., Mirra, S. S., Beal, M. F., Yang, C.-C., Gearing, M., Salvo, R., et al. (1993) · Genomics · doi:10.1006/geno.1993.1299 · Cited by 450 · see citing works
Decreases in regional cerebral blood flow with normal aging
Martin, A. J., Friston, K. J., Colebatch, J. G., & Frackowiak, R. S. J. (1991) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1991.121 · Cited by 393 · see citing works
Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid
Brouillet, E., Jenkins, B. G., Hyman, B. T., Ferrante, R. J., Kowall, N. W., Srivastava, R., Roy, D. S., Rosen, B. R., & Beal, M. F. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb05859.x · Cited by 367 · see citing works
Assays for 8-hydroxy-2′-deoxyguanosine: A biomarker of in vivo oxidative DNA damage
Shigenaga, M. K., & Ames, B. N. (1991) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(91)90078-h · Cited by 365 · see citing works
Dyrks, T., Dyrks, E., Hartmann, T., Masters, C. L., & Beyreuther, K. T. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)37174-1 · Cited by 343 · see citing works
Regional cerebral blood flow and oxygen consumption in human aging
Pantano, P., Baron, J. C., Lebrun-Grandié, P., Duquesnoy, N., Bousser, M. G., & Comar, D. (1984) · Stroke · doi:10.1161/01.str.15.4.635 · Cited by 341 · see citing works
Cooper, J. A. D., Mann, V. M., & Schapira, A. H. V. (1992) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(92)90270-u · Cited by 335 · see citing works
Liver mitochondrial respiratory functions decline with age
Yen, T., Chen, Y.-S., King, K.-L., Yeh, S.-H., & Wei, Y. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)92701-0 · Cited by 323 · see citing works
Beal, M. F., Matson, W. R., Swartz, K. J., Gamache, P. H., & Bird, E. D. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb03143.x · Cited by 312 · see citing works
Beal, M. F., Brouillet, E., Jenkins, B. G., Henshaw, R., Rosen, B. R., & Hyman, B. T. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03633.x · Cited by 297 · see citing works
Age-associated oxygen damage and mutations in mitochondrial DNA in human hearts
Hayakawa, M., Hattori, K., Sugiyama, S., & Ozawa, T. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)92300-m · Cited by 283 · see citing works
Regional Cerebral Oxygen Consumption, Blood Flow, and Blood Volume in Healthy Human Aging
Marchal, G., Rioux, P. P., Petit-Taboué, M.-C., Sette, G., Travère, J.-M., Poec, C. L., Courtheoux, P., Derlon, J.-M., & Baron, J. (1992) · Archives of Neurology · doi:10.1001/archneur.1992.00530340029014 · Cited by 271 · see citing works
Age‐Dependent Impairment of Mitochondrial Function in Primate Brain
Bowling, A. C., Mutisya, E. M., Walker, L. C., Price, D. L., Cork, L. C., & Beal, M. H. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb13430.x · Cited by 263 · see citing works
Local cerebral glucose utilization in the normal conscious macaque monkey
Kennedy, C., Sakurada, O., Shinohara, M., Jehle, J. W., & Sokoloff, L. (1978) · Annals of Neurology · doi:10.1002/ana.410040402 · Cited by 245 · see citing works
Multiple mitochondrial DNA deletions in an elderly human individual
Zhang, C., Baumer, A., Maxwell, R. J., Linnane, A. W., & Nagley, P. (1992) · FEBS Letters · doi:10.1016/0014-5793(92)80321-7 · Cited by 214 · see citing works
Age-associated accumulation of 8-hydroxydeoxyguanosine in mitochondrial DNA of human diaphragm
Hayakawa, M., Torii, K., Sugiyama, S., Tanaka, M., & Ozawa, T. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)91921-x · Cited by 199 · see citing works
An integrated theory of aging as the result of mitochondrial-DNA mutation in differentiated cells
Miquel, J. (1991) · Archives of Gerontology and Geriatrics · doi:10.1016/0167-4943(91)90022-i · Cited by 197 · see citing works
Magnetic Resonance Imaging of Brain Iron
Drayer, B. P., Burger, P. C., Darwin, R. H., Riederer, S. J., Herfkens, R. J., & Johnson, G. A. (1986) · Europe PMC (PubMed Central) · Cited by 176 · see citing works
Influence of Mitochondrial Radical Formation on Energy‐Linked Respiration
Nohl, H., Breuninger, V., & HEGNER, D. (1978) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1978.tb12615.x · Cited by 165 · see citing works
Subacute necrotizing encephalopathy
Shoffner, J. M., Fernhoff, P. M., Krawiecki, N., Caplan, D. B., Holt, P., Koontz, D. A., Takei, Y., Newman, N. J., Ortiz, R. G., Polak, M., et al. (1992) · Neurology · doi:10.1212/wnl.42.11.2168 · Cited by 154 · see citing works
Hayakawa, M., Ogawa, T., Sugiyama, S., Tanaka, M., & Ozawa, T. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)90893-c · Cited by 131 · see citing works
Age-related Decrease in Respiratory Muscle Mitochondrial Function in Rats
Torii, K., Sugiyama, S., Takagi, K., Satake, T., & Ozawa, T. (1992) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb/6.1.88 · Cited by 82 · see citing works
Diagnosis of Duchenne and Becker Muscular Dystrophies by Polymerase Chain Reaction
Chamberlain, J. S., Chamberlain, J. S., Fenwick, R. G., Ward, P. A., Caskey, C. T., Dimnik, L. S., Bech‐Hansen, N. T., Hoar, D. I., Richards, S., Covone, A. E., et al. (1992) · JAMA · doi:10.1001/jama.1992.03480190051030 · Cited by 74 · see citing works
The human 18S ribosomal RNA gene: evolution and stability.
Gonzalez, I. L., & Schmickel, R. D. (1986) · PubMed · Cited by 73 · see citing works
Giles, R. E., Stroynowski, I., & Wallace, D. C. (1980) · Somatic Cell and Molecular Genetics · doi:10.1007/bf01539155 · Cited by 70 · see citing works
Age-dependent changes in rat brain mitochondria of synaptic and non-synaptic origins
Harmon, H. J., Nank, S., & Floyd, R. A. (1987) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(87)90076-5 · Cited by 56 · see citing works
Differential expression of cytochrome oxidase (COX) genes in different regions of monkey brain
Chandrasekaran, K., Stoll, J., Giordano, T., Atack, J. R., Matocha, M. F., Brady, D. R., & Рапопорт, С. И. (1992) · Journal of Neuroscience Research · doi:10.1002/jnr.490320313 · Cited by 44 · see citing works
Chandrasekaran, K., Stoll, J., Brady, D. R., & Rapoport, S. I. (1992) · Brain Research · doi:10.1016/0006-8993(92)90070-p · Cited by 32 · see citing works
Flagged first, then by citations
1 of the 50 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Oxidative Stress, Glutamate, and Neurodegenerative Disorders
Coyle, J. T., & Puttfarcken, P. (1993) · Science · doi:10.1126/science.7901908 · Cited by 3,762 · see citing works
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185 · see citing works
“These mtDNA mutations can be attributed to oxidative damage, at least in the brain, since the human brain mtDNA shows a marked age-related increase in oxidative damage (135).”
BackgroundMitochondrial diseases in man and mouse
Wallace, D. C. (1999) · Science · doi:10.1126/science.283.5407.1482 · Cited by 3,060 · see citing works
Oxidative stress hypothesis in Alzheimer’s disease
Markesbery, W. R. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00629-6 · Cited by 2,383 · see citing works
Oxidative damage and mitochondrial decay in aging.
Shigenaga, M. K., Hagen, T. M., & Ames, B. N. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.10771 · Cited by 2,055 · see citing works
Gene regulation and DNA damage in the ageing human brain
Lu, T., Pan, Y., Kao, S.-Y., Li, C., Kohane, I., Chan, J., & Yankner, B. A. (2004) · Nature · doi:10.1038/nature02661 · Cited by 1,874 · see citing works
“A previous study showed that there is also substantial oxidative damage to mitochondrial DNA in the ageing human brai”
BackgroundAging, energy, and oxidative stress in neurodegenerative diseases
Beal, M. F. (1995) · Annals of Neurology · doi:10.1002/ana.410380304 · Cited by 1,434 · see citing works
Oxidative DNA damage and disease: induction, repair and significance
Evans, M. D., Dizdaroglu, M., & Cooke, M. S. (2004) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2003.11.001 · Cited by 1,372 · see citing works
Pathogenesis of parkinson's disease: dopamine, vesicles and α-synuclein
Lotharius, J., & Brundin, P. (2002) · Nature reviews. Neuroscience · doi:10.1038/nrn983 · Cited by 1,283 · see citing works
“, and oxidative damage to mitochondrial DNA increases up to 15-fold compared with nuclear DN”
BackgroundGlutathione, oxidative stress and neurodegeneration
Schulz, J. B., Lindenau, J. H., Seyfried, J., & DICHGANS, J. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01595.x · Cited by 1,215 · see citing works
“Direct evidence for age-dependent increase in oxidative damage to mitochondrial DNA comes from measurements of 8-hydroxy-2 0-deoxyguanosine (8OH2 0dG), which is an oxidized form of deoxyguanosine that occurs following attack by a variety of free radicals [12].”
BackgroundKasai, H. (1997) · Mutation Research/Reviews in Mutation Research · doi:10.1016/s1383-5742(97)00035-5 · Cited by 1,140 · see citing works
MITOCHONDRIAL DNA MAINTENANCE IN VERTEBRATES
Shadel, G. S., & Clayton, D. A. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.409 · Cited by 1,059 · see citing works
Endogenous DNA damage in humans: a review of quantitative data
Bont, R. D. (2004) · Mutagenesis · doi:10.1093/mutage/geh025 · Cited by 1,065 · see citing works
Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease
Mecocci, P., MacGarvey, U., & Beal, M. F. (1994) · Annals of Neurology · doi:10.1002/ana.410360510 · Cited by 1,037 · see citing works
Neurodegenerative diseases and oxidative stress
Emerit, J., Edeas, M. A., & Bricaire, F. (2003) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2003.11.004 · Cited by 1,031 · see citing works
Oxidative Stress, Mitochondrial Dysfunction, and Aging
Cui, H., Kong, Y., & Zhang, H. (2011) · Journal of Signal Transduction · doi:10.1155/2012/646354 · Cited by 1,036 · see citing works
Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer’s disease
Bartzokis, G. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.03.001 · Cited by 968 · see citing works
“[151] Mecocci P, MacGarvey U, Kaufman AE, Koontz D, Shoffner JM, Wallace DC, et al.”
BackgroundCancer risk and oxidative DNA damage in man
Loft, S. H., & Poulsen, H. E. (1996) · Journal of Molecular Medicine · doi:10.1007/bf00207507 · Cited by 955 · see citing works
Kregel, K. C., & Zhang, H. J. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00327.2006 · Cited by 883 · see citing works
“An increased presence of oxidative damage to mitochondrial DNA has been found in skeletal muscle and brain of older individuals (165, 241), and these observations are consistent with recent findings demonstrating a decline in mitochondrial function in older humans (48, 206).”
ResultBrowne, S. E., Bowling, A. C., Macgarvey, U., Baik, M. J., Berger, S. C., Muquit, M. M. K., Bird, E. D., & Beal, M. F. (1997) · Annals of Neurology · doi:10.1002/ana.410410514 · Cited by 885 · see citing works
Self-citationSuperoxide accelerates DNA damage by elevating free-iron levels
Keyer, K., & Imlay, J. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13635 · Cited by 841 · see citing works
Evidence of Increased Oxidative Damage in Both Sporadic and Familial Amyotrophic Lateral Sclerosis
Ferrante, R. J., Browne, S. E., Shinobu, L. A., Bowling, A. C., Baik, M. J., MacGarvey, U. M., Kowall, N. W., Brown, R. H., & Beal, M. F. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69052064.x · Cited by 808 · see citing works
Oxidative Alterations in Alzheimer's Disease
Markesbery, W. R., & Carney, J. M. (1999) · Brain Pathology · doi:10.1111/j.1750-3639.1999.tb00215.x · Cited by 789 · see citing works
Does oxidative damage to DNA increase with age?
Hamilton, M. L., Van Remmen, H., Drake, J. A., Yang, H., Guo, Z. M., Kewitt, K., Walter, C. A., & Richardson, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171202698 · Cited by 768 · see citing works
Review: Alzheimer's Amyloid β-Peptide-Associated Free Radical Oxidative Stress and Neurotoxicity
Varadarajan, S., Yatin, S., Aksenova, M., & Butterfield, D. A. (2000) · Journal of Structural Biology · doi:10.1006/jsbi.2000.4274 · Cited by 735 · see citing works
Interrelation of Oxidative Stress and Inflammation in Neurodegenerative Disease: Role of TNF
Fischer, R., & Maier, O. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/610813 · Cited by 744 · see citing works
“Therefore, insufficient clearance is associated with accumulation of damaged molecules and organelles with increasing age [43, 44].”
BackgroundRNA Oxidation Is a Prominent Feature of Vulnerable Neurons in Alzheimer’s Disease
Nunomura, A., Perry, G., Pappolla, M., Wade, R., Hirai, K., Chiba, S., & Smith, M. A. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-06-01959.1999 · Cited by 768 · see citing works
“The OD in an area comprising the cytoplasm and nucleus was determined with a Quantimet 570C Image Processing and Analysis System (Leica) linked to a C OHU solid state camera mounted on a Leitz Laborlux 12 M E ST microscope, according to the methods of Masliah et al. (1990) .”
BackgroundMethodResultBains, J. S., & Shaw, C. A. (1997) · Brain Research Reviews · doi:10.1016/s0165-0173(97)00045-3 · Cited by 716 · see citing works
Base excision repair of oxidative DNA damage and association with cancer and aging
Maynard, S., Schurman, S. H., Harboe, C., de Souza-Pinto, N. C., & Bohr, V. A. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn250 · Cited by 685 · see citing works
Oxidative stress in brain aging, neurodegenerative and vascular diseases: An overview
Mariani, E., Polidori, M. C., Cherubini, A., & Mecocci, P. (2005) · Journal of Chromatography B · doi:10.1016/j.jchromb.2005.04.023 · Cited by 682 · see citing works
Yankner, B. A., Lu, T., & Loerch, P. (2008) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.2.010506.092044 · Cited by 677 · see citing works
Role of mitochondria in oxidative stress and ageing
Lenaz, G. (1998) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(98)00120-0 · Cited by 650 · see citing works
Lovell, M. A., Ehmann, W. D., Butler, S. M., & Markesbery, W. R. (1995) · Neurology · doi:10.1212/wnl.45.8.1594 · Cited by 644 · see citing works
Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory
Massaad, C. A., & Klann, E. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3208 · Cited by 635 · see citing works
“ROS are typically categorized as neurotoxic molecules and exert their detrimental effects via oxidation of essential molecules such as enzymes and cytoskeletal proteins (69, 142, 285).”
BackgroundOxidative stress in ALS: Key role in motor neuron injury and therapeutic target
Barber, S. C., & Shaw, P. J. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.11.018 · Cited by 617 · see citing works
“However, cumulative oxidative damage over time may be responsible for the decreased mitochondrial efficiency and the high mutation rate of mitochondrial DNA that are thought to contribute to the aging process [46,47,113].”
BackgroundEvidence of neuronal oxidative damage in Alzheimer's disease.
Good, P. F., Werner, P., Hsu, A., Olanow, C. W., & Perl, D. P. (1996) · Europe PMC (PubMed Central) · Cited by 600 · see citing works
Glia and their cytokines in progression of neurodegeneration
Mrak, R. E., & Griffin, W. S. T. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.05.010 · Cited by 592 · see citing works
Mammalian Mitochondria and Aging: An Update
Kauppila, T. E. S., Kauppila, J. H. K., & Larsson, N.-G. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.017 · Cited by 578 · see citing works
“Traditionally, PGC1a has been thought to mediate exercise and dietary restriction-induced mitochondrial biogenesis, but these assumptions have recently been questioned (Finley et al., 2012; Geng et al., 2010; Leick et al., 2008; Miller et al., 2012; Rowe et al., 2012).”
Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production
Trifunovic, A., Hansson, A., Wredenberg, A., Rovio, A. T., Dufour, E., Khvorostov, I., Spelbrink, J. N., Wibom, R., Jacobs, H. T., & Larsson, N.-G. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508886102 · Cited by 555 · see citing works
Barja, G., & Herrero, A. (2000) · The FASEB Journal · doi:10.1096/fasebj.14.2.312 · Cited by 540 · see citing works
“The levels of 8-oxodG found in the mtDNA of old individuals, which are between 2and 15-fold higher than those of young ones according to the different reports (5, 6, 13, 15, 16), as well as those found in the mtDNA of short-lived species in this investigation, would be quickly reached in the absence of repair systems.”
BackgroundResultInfluentialMitochondrial DNA sequence variation in human evolution and disease.
Wallace, D. C. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.19.8739 · Cited by 520 · see citing works
Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer's disease
Lovell, M. A., & Markesbery, W. R. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm821 · Cited by 515 · see citing works
“(36), who used HPLC/ECD to show an age-dependent increase in levels of 8-OHG in nDNA and mDNA specimens from cerebral cortex of 10 normal control subjects aged 42–97.”
Hensley, K., Maidt, M. L., Yu, Z., Sang, H., Markesbery, W. R., & Floyd, R. A. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-20-08126.1998 · Cited by 508 · see citing works
“…carbonyl content and lipid and DNA oxidation products and by inactivation of sensitive enzymes (Oliver et al., 1987; C. Smith et al., 1991, 1992; Mecocci et al., 1993; Balazs and Leon, 1994; Chen et al., 1994; Hensley et al., 1995; Lovell et al., 1995; M. Smith et al., 1996; Butterfield et al.,…”
BackgroundBarja, G. (1999) · Journal of Bioenergetics and Biomembranes · doi:10.1023/a:1005427919188 · Cited by 494 · see citing works
Oxidative stress in ALS: A mechanism of neurodegeneration and a therapeutic target
Barber, S. C., Mead, R. J., & Shaw, P. J. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2006.03.008 · Cited by 475 · see citing works
“Some components of the electron transport chain are encoded by mitochondrial DNA, which has a 10-fold higher mutation rate than nuclear DNA [10].”
BackgroundSas, K., Robotka, H., Toldi, J., & Vécsei, L. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2007.01.033 · Cited by 465 · see citing works
Age-dependent increases in oxidative damage to DNA, lipids, and proteins in human skeletal muscle
Mecocci, P., Fanò, G., Fulle, S., MacGarvey, U. M., Shinobu, L. A., Polidori, M. C., Cherubini, A., Vecchiet, J., Senin, U., & Beal, M. F. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00208-1 · Cited by 461 · see citing works
Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer's disease
Wang, J., Xiong, S., Xie, C., Markesbery, W. R., & Lovell, M. A. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03053.x · Cited by 452 · see citing works
“Previous studies show that there is more 8- OHdG in mtDNA than in nDNA and there is a significant increase in aged subjects compared to younger subjects (Mecocci et al. 1993, 1994).”
BackgroundMethodResultInfluentialDependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age
Hansford, R. G., Hogue, B. A., & Mildaziene, V. (1997) · Journal of Bioenergetics and Biomembranes · doi:10.1023/a:1022420007908 · Cited by 447 · see citing works
Haas, R. H., Nasirian, F., Nakano, K., Ward, D., Pay, M., Hill, R., & Shults, C. W. (1995) · Annals of Neurology · doi:10.1002/ana.410370604 · Cited by 435 · see citing works
Hagen, T. M., Yowe, D. L., Bartholomew, J. C., Wehr, C. M., Katherine, L. B. B., Park, J.-Y., & Ames, B. N. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.7.3064 · Cited by 434 · see citing works
Elevated 4-Hydroxynonenal in Ventricular Fluid in Alzheimer’s Disease
Lovell, M. A., Ehmann, W. D., Mattson, M. P., & Markesbery, W. R. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00108-5 · Cited by 413 · see citing works
Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia
Calabrese, V., Lodi, R., Tonon, C., D’Agata, V., Sapienza, M. A., Scapagnini, G., Mangiameli, A., Pennisi, G., Stella, A. M. G., & Butterfield, D. A. (2005) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2005.03.012 · Cited by 407 · see citing works
“[71] Mecocci P, MacGarvey U, Kaufman AE, Koontz D, Shoffner JM,”
BackgroundAmes, B. N., Shigenaga, M. K., & Hagen, T. M. (1995) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/0925-4439(95)00024-x · Cited by 391 · see citing works
Mitochondrial dysfunction and oxidative stress: cause and consequence of epileptic seizures
Patel, M. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.08.021 · Cited by 395 · see citing works
Reactive oxygen species and mitochondrial diseases
Kirkinezos, I. G., & Moraes, C. T. (2001) · Seminars in Cell and Developmental Biology · doi:10.1006/scdb.2001.0282 · Cited by 385 · see citing works
Furda, A. M., Santos, J. H., Meyer, J. N., & Houten, B. V. (2014) · Methods in molecular biology · doi:10.1007/978-1-62703-739-6_31 · Cited by 384 · see citing works
WANAGAT, J., CAO, Z., PATHARE, P., & AIKEN, J. M. (2001) · The FASEB Journal · doi:10.1096/fj.00-0320com · Cited by 378 · see citing works
“age in human brain (11), diaphragm (12), heart (13,”
BackgroundGabuzda, D., Busciglio, J., Chen, L. B., Matsudaira, P., & Yankner, B. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36875-8 · Cited by 373 · see citing works
Bioenergetic and oxidative stress in neurodegenerative diseases
Bowling, A. C., & Beal, M. F. (1995) · Life Sciences · doi:10.1016/0024-3205(95)00055-b · Cited by 364 · see citing works
Autophagy as an essential cellular antioxidant pathway in neurodegenerative disease
Giordano, S. S., Darley-Usmar, V. M., & Zhang, J. (2013) · Redox Biology · doi:10.1016/j.redox.2013.12.013 · Cited by 366 · see citing works
Are reactive oxygen species involved in Alzheimer's disease?
Benzi, G. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00066-n · Cited by 365 · see citing works
Kennedy, S. R., Salk, J. J., Schmitt, M. W., & Loeb, L. A. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003794 · Cited by 363 · see citing works
“In addition, DNA damage, predominantly in the form of 8-hydroxy-29-deoxyguanosine (8-oxo-dG) [16], increases with age in both nuclear and mitochondrial DNA [17,18,19,20].”
BackgroundOxidative damage to mitochondrial DNA and its relationship to ageing
Richter, C. (1995) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/1357-2725(95)00025-k · Cited by 351 · see citing works
Vitamin E and Cognitive Decline in Older Persons
Morris, M. C., Evans, D. A., Bienias, J. L., Tangney, C. C., & Wilson, R. S. (2002) · Archives of Neurology · doi:10.1001/archneur.59.7.1125 · Cited by 346 · see citing works
Mitochondria, oxidative stress, and temporal lobe epilepsy
Waldbaum, S., & Patel, M. (2009) · Epilepsy Research · doi:10.1016/j.eplepsyres.2009.09.020 · Cited by 345 · see citing works
“8-OHdG, an oxidatively modified guanine adduct, is one of the most common adducts formed from oxidation of DNA (Dizdaroglu, 1991) and has been used as an index of oxidative DNA damage with the ratio of steady state levels of 8-OHdG to 2-deoxyguanine (2-dG) (Shigenaga et al., 1990; Mecocci et al., 1993; Giulivi et al.,…”
Oxidative damage to macromolecules in human Parkinson disease and the rotenone model
Sanders, L. H., & Greenamyre, J. T. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.01.003 · Cited by 347 · see citing works
“These results are in contrast to previous results that show an increase in 8-oxo-dG with age in both nuclear and mitochondrial DNA from human postmortem brains [28].”
Role of oxidative DNA damage in cancer initiation and promotion.
Poulsen, H. E., Priemé, H., & Loft, S. H. (1998) · PubMed · Cited by 343 · see citing works
The role of mitochondrial oxidative stress in aging
Sastre, J. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00184-9 · Cited by 342 · see citing works
Traumatic Brain Injury: Oxidative Stress and Neuroprotection
Cornelius, C., Crupi, R., Calabrese, V., Graziano, A., Milone, P., Pennisi, G., Radak, Z. O., Calabrese, E. J., & Cuzzocrea, S. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4981 · Cited by 343 · see citing works
“Mecocci and co-workers have reported that aging results in significant increases in nuclear and mitochondrial 8-oxoG levels in human cerebral cortex and cerebellum (113).”
Mitochondrial DNA repair and aging
Mandavilli, B. S., Santos, J. H., & Houten, B. V. (2002) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(02)00220-8 · Cited by 338 · see citing works
“[16] P.”
BackgroundInfluentialIncreased oxidative damage to DNA in ALS patients
Bogdanov, M. B., Brown, R. H., Matson, W. R., Smart, R. J., Hayden, D. L., O’Donnell, H. C., Beal, M. F., & Cudkowicz, M. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00349-x · Cited by 334 · see citing works
Lu, F., Selak, M. A., O'Connor, J. J., Croul, S. E., Lorenzana, C., Butunoi, C., & Kálmán, B. (2000) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(00)00343-9 · Cited by 331 · see citing works
Evidence of Oxidative Stress in the Pathogenesis of Fuchs Endothelial Corneal Dystrophy
Jurkunas, U. V., Bitar, M. S., Funaki, T., & Azizi, B. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.100279 · Cited by 325 · see citing works
Glutamate and Parkinson’s disease
Blandini, F., Porter, R. H. P., & Greenamyre, J. T. (1996) · Molecular Neurobiology · doi:10.1007/bf02740748 · Cited by 326 · see citing works
“Moreover, in subjects over age 70, there is 15-fold more damage in mtDNA (88).”
BackgroundNagai, T., Yamada, K., Kim, H., Kim, Y., Noda, Y., Imura, A., Nabeshima, Y., & Nabeshima, T. (2002) · The FASEB Journal · doi:10.1096/fj.02-0448fje · Cited by 312 · see citing works
“Oxidative damage is considered a likely cause of age-associated brain dysfunction because the brain is particularly vulnerable to oxidative stress due to a relatively high rate of generation of reactive oxygen species (ROS) without commensurate levels of antioxidative defense (4, 5).”
BackgroundCarriedo, S. G., Sensi, S. L., Yin, H. Z., & Weiss, J. H. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-01-00240.2000 · Cited by 311 · see citing works
Mitochondrial superoxide production in kainate-induced hippocampal damage
Liang, L., Ho, Y.-S., & Patel, M. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00397-3 · Cited by 309 · see citing works
Brain aging, Alzheimer's disease, and mitochondria
Swerdlow, R. H. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.08.012 · Cited by 306 · see citing works
“Oxidative stress may partly account for mtDNA's relatively high mutation rate; mtDNA acquires mutations at approximately 10 times the rate of nuclear DNA [121].”
BackgroundPlasma antioxidants and longevity: a study on healthy centenarians
Mecocci, P., Polidori, M. C., Troiano, L., Cherubini, A., Cecchetti, R., Pini, G., Straatman, M., Monti, D., Stahl, W., Sies, H., et al. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00246-x · Cited by 306 · see citing works
Mitochondrial dysfunction and oxidative stress in aging and neurodegenerative disease
Albers, D. S., & Beal, M. F. (2000) · Springer eBooks · doi:10.1007/978-3-7091-6781-6_16 · Cited by 297 · see citing works
Mitochondria, oxidative stress and aging
Sastre, J., Pallardó, F. V., de la Asunción, J. G., & Viña, J. (2000) · Free Radical Research · doi:10.1080/10715760000300201 · Cited by 292 · see citing works
Lovell, M. A., Gabbita, S. P., & Markesbery, W. R. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0720771.x · Cited by 291 · see citing works
Fuchs endothelial corneal dystrophy: The vicious cycle of Fuchs pathogenesis
Tone, S. O., Kocaba, V., Böhm, M., Wylęgała, A., White, T. L., & Jurkunas, U. V. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100863 · Cited by 293 · see citing works
Exercise counteracts declining hippocampal function in aging and Alzheimer's disease
Intlekofer, K. A., & Cotman, C. W. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.06.011 · Cited by 286 · see citing works
“Remarkably, physical activity has been shown to attenuate mitochondrial DNA (mtDNA) deletions and point mutations that correlate with declining mitochondrial function in aging and AD (Coskun et al., 2004; Mecocci et al., 1993, 1994).”
BackgroundCalabrese, V., Bates, T. E., & Stella, A. M. G. (2000) · Neurochemical Research · doi:10.1023/a:1007604414773 · Cited by 285 · see citing works
“Vitamin E also blocked Aβ-induced inhibition of transmembrane protein function, including ion-motive ATPases, glucose and glutamate transporters, G-protein coupled signal transduction and the energy-related enzyme creatine kinase, and the methionine residue 35 of A β(1-42) and Aβ(1-40) was shown to be critical to the…”
Benzi, G., & Moretti, A. (1995) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(94)00244-e · Cited by 283 · see citing works
Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo
Schulz, J. B., Matthews, R., Jenkins, B. G., Ferrante, R. J., Siwek, D. F., Henshaw, D. R., Cipolloni, P. B., Mecocci, P., Kowall, N. W., & Rosen, B. R. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-12-08419.1995 · Cited by 281 · see citing works
“Eight saline treated and eight 3-NP (20 mg/kg) treated 250 gm male Sprague- Dawley rats were sacrificed at 3 hr and whole brain DNA was extracted and S-hydroxy-2-deoxyguanosine was measured as previously described (Mecocci et al., 1993).”
BackgroundMethodInfluentialMitochondria and degenerative disorders
Orth, M., & Schapira, A. H. V. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1425 · Cited by 278 · see citing works
Spencer, J. P. E., Jenner, A. M., Aruoma, O. I., Evans, P., Kaur, H., Dexter, D. T., Jenner, P. G., Lees, A. J., Marsden, D. C., & Halliwell, B. B. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)01056-0 · Cited by 278 · see citing works
Papa, S. (1996) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(96)00077-1 · Cited by 264 · see citing works
Wei, Y., Lu, C., Lee, H., Pang, C., & Ma, Y. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb09899.x · Cited by 265 · see citing works
“On the other hand, the insertion sites of the tandem duplications in the D-loop region of human mtDNA have been found to be localized in the regions containing either a poly C run or a direct repeat sequence.(63,82) This finding suggests that slipped replication frequently occurs at the poly C stretches in the D-loop…”
Tyrosine Hydroxylase and Parkinson’s Disease
Haavik, J., & Toska, K. (1998) · Molecular Neurobiology · doi:10.1007/bf02741387 · Cited by 263 · see citing works
“Furthermore, an age-dependent accumulation of oxidized nucleotides in mitochondrial DNA (mtDNA) (Mecocci et al., 1993) and an increased frequency of mtDNA deletion mutations in the putamen, caudate, or SN, relative to other brain regions such as the cerebellum, has been reported (Soong et al.”
Calabrese, V., Scapagnini, G., Giuffrida Stella, A. M., Bates, T. E., & Clark, J. B. (2001) · Neurochemical Research · doi:10.1023/a:1010955807739 · Cited by 263 · see citing works
Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment
Wang, J., Markesbery, W. R., & Lovell, M. A. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03615.x · Cited by 260 · see citing works
“A modified procedure of Mecocci et al. (1993) was used to isolate DNA.”
MethodResultMitochondrial oxidative stress, aging and caloric restriction: The protein and methionine connection
Pamplona, R., & Barja, G. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.01.009 · Cited by 255 · see citing works
DNA repair in neurons: So if they don’t divide what's to repair?
Fishel, M. L., Vasko, M. R., & Kelley, M. R. (2006) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2006.06.007 · Cited by 256 · see citing works
Mecocci, P., Boccardi, V., Cecchetti, R., Bastiani, P., Scamosci, M., Ruggiero, C., & Baroni, M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170732 · Cited by 256 · see citing works
“8-hydroxy-2’-deoxyguanosine (OH8dG) Measured in nDNA and mtDNA from cerebral cortex and cerebellum in humans: higher values with aging [54], threefold increase in subjects with AD compared to controls [55].”
The free radical flux theory of sleep
Reimund, E. (1994) · Medical Hypotheses · doi:10.1016/0306-9877(94)90071-x · Cited by 253 · see citing works
Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment
Mangialasche, F., Polidori, M. C., Monastero, R., Ercolani, S., Camarda, C., Cecchetti, R., & Mecocci, P. (2009) · Ageing Research Reviews · doi:10.1016/j.arr.2009.04.002 · Cited by 247 · see citing works
“Mecocci et al. (1993) were the first group to demonstrate a progressive age-related accumulation of 8-OHdG in the cerebral cortex of cognitively normal subjects, aged 42–97 years.”
- Authors
- Mecocci, P., MacGarvey, U., Kaufman, A. E., Koontz, D., Shoffner, J. M., Wallace, D. C., & Beal, M. F.
- Affiliations
- Harvard University (US)
- Emory University (US)
- Corresponding author
- Beal, M. Flint
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 1993-10
- Volume
- 34
- Issue
- 4
- Pages
- 609-616
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2130753450
- Cited by
- 757
- References
- 50
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 12 · 2023: 12 · 2022: 15 · 2021: 18 · 2020: 19 · 2019: 22 · 2018: 17 · 2017: 16 · 2016: 19 · 2015: 18 · 2014: 24 · 2013: 29 · 2012: 22
- FWCI
- 7.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (16367)
- National Institute on Aging (IP50 AG05134)
- National Institute of Neurological Disorders and Stroke (NS-21328, R01NS021328)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- oxidative DNA damage, mitochondrial DNA, 8-hydroxy-2'-deoxyguanosine, brain aging, cerebral cortex, cerebellum, nuclear DNA, age-related accumulation, neurodegenerative diseases
- MeSH terms
- 8-Hydroxy-2'-Deoxyguanosine, Adult, Aged, Aged, 80 and over, Aging, Brain, Cell Nucleus, Deoxyguanosine, DNA, DNA, Mitochondrial, Female, Humans, Male, Middle Aged, Oxidation-Reduction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
