Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age
Abstract
We have examined the role of somatic mitochondrial DNA (mtDNA) mutations in human ageing by quantitating the accumulation of the common 4977 nucleotide pair (np) deletion (mtDNA4977) in the cortex, putamen and cerebellum. A significant increase in the mtDNA4977 deletion was seen in elderly individuals. In the cortex, the deleted to total mtDNA ratio ranged from 0.00023 to 0.012 in 67-77 year old brains and up to 0.034 in subjects over 80. In the putamen, the deletion level ranged from 0.0016 to 0.010 in 67 to 77 years old up to 0.12 in individuals over the age of 80. The cerebellum remained relatively devoid of mtDNA deletions. Similar changes were observed with a different 7436 np deletion. These changes suggest that somatic mtDNA deletions might contribute to the neurological impairment often associated with ageing.
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Age-related mtDNA changes occur within the human brain.
“Evidence indicates age-related mtDNA changes do in fact occur within the human brain.”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [115]
Levels of a 5-kilobase deletion that particularly affects mtDNA COX genes increase with age.
“Levels of a 5-kilobase deletion that particularly affects mtDNA COX genes increase with age [115].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [115]
Cites
Biometry: The Principles and Practice of Statistics in Biological Research
Sokal, R. R., & Rohlf, F. J. (1969) · Cited by 20,963 · see citing works
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · 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
Diseases of the mitochondrial DNA
Wallace, D. C. (1992) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.61.070192.005523 · Cited by 1,319 · see citing works
Self-citationMitochondrial 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
Self-citationEvans, 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
Detection of a specific mitochondrial DNA deletion in tissues of older humans
Cortopassi, G. A., & Arnheim, N. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.23.6927 · Cited by 785 · 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
Aging and Extrapyramidal Function
McGeer, P. L., McGeer, E. G., & Suzuki, J. S. (1977) · Archives of Neurology · doi:10.1001/archneur.1977.00500130053010 · Cited by 648 · see citing works
Cytochrome oxidase deficiency in Alzheimer’s disease
Parker, W. D., Filley, C. M., & Parks, J. K. (1990) · Neurology · doi:10.1212/wnl.40.8.1302 · Cited by 598 · see citing works
Mitochondrial mutations may increase oxidative stress: Implications for carcinogenesis and aging?
Bandy, B., & Davison, A. J. (1990) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(90)90152-9 · Cited by 550 · see citing works
Shoffner, J. M., Lott, M. T., Voljavec, A. S., Soueidan, S. A., Costigan, D. A., & Wallace, D. C. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.20.7952 · Cited by 505 · see citing works
Self-citationFree radicals, aging, and degenerative diseases
Sohal, R. S. (1987) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(87)90041-4 · Cited by 383 · see citing works
Association of mitochondrial DNA damage with aging and coronary atherosclerotic heart disease
Corral‐Debrinski, M., Shoffner, J. M., Lott, M. T., & Wallace, D. C. (1992) · Mutation Research/DNAging · doi:10.1016/0921-8734(92)90021-g · Cited by 360 · see citing works
Self-citationCorral‐Debrinski, M. (1991) · JAMA · doi:10.1001/jama.266.13.1812 · Cited by 341 · see citing works
Self-citationEndogenous DNA damage as related to cancer and aging
Ames, B. N. (1989) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(89)90196-6 · Cited by 327 · 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
Free radicals, aging, and degenerative diseases
Johnson, J. E., Walford, R. L., Harman, D., & Miquel, J. (1986) · Medical Entomology and Zoology · Cited by 310 · see citing works
Free radicals and myocardial ischemia: Overview and outlook
McCord, J. M. (1988) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(88)90005-6 · Cited by 286 · see citing works
Müller‐Höcker, J. (1990) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(90)90006-9 · Cited by 284 · see citing works
Müller‐Höcker, J. (1989) · PubMed Central · Cited by 280 · see citing works
Hattori, K., Tanaka, M., Sugiyama, S., Obayashi, T., Ito, T., Satake, T., Hanaki, Y., Asai, J., Nagano, M., & Ozawa, T. (1991) · American Heart Journal · doi:10.1016/0002-8703(91)90020-i · Cited by 264 · see citing works
Reduction in regional cerebral metabolic rate of oxygen during human aging.
Yamaguchi, T., Kanno, I., Uemura, K., Shishido, F., Inugami, A., Ogawa, T., Murakami, M. T., & Suzuki, K. (1986) · Stroke · doi:10.1161/01.str.17.6.1220 · Cited by 260 · see citing works
Imaging of the aging brain. Part I. Normal findings.
Drayer, B. P. (1988) · Radiology · doi:10.1148/radiology.166.3.3277247 · Cited by 256 · see citing works
Neuropathologic and clinical features of Parkinson's disease in Alzheimer's disease patients
Ditter, S. M., & Mirra, S. S. (1987) · Neurology · doi:10.1212/wnl.37.5.754 · Cited by 250 · see citing works
Ageing-associated 5 kb deletion in human liver mitochondrial DNA
Yen, T.-C., Su, J.-H., King, K.-L., & Wei, Y.-H. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)91788-e · Cited by 248 · 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
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
Pikó, L., Hougham, A. J., & Bulpitt, K. J. (1988) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(88)90037-1 · Cited by 191 · 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
Ozawa, T., Tanaka, M., Sugiyama, S., Hattori, K., Ito, T., Ohno, K., Takahashi, A., Sato, W., Takada, G., Mayumi, B., et al. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)92166-w · Cited by 174 · see citing works
Yoshii, F., Barker, W. W., Chang, J. Y., Loewenstein, D., Apicella, A., Smith, D. D., Boothe, T. E., Ginsberg, M. D., Pascal, S., & Duara, R. (1988) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1988.112 · Cited by 168 · see citing works
Report of the committee on human mitochondrial DNA
Wallace, D. C., Lott, M. T., Shoffner, J. M., Torroni, A., & Malik, S. (2008) · Cytogenetics and Cell Genetics · doi:10.1159/000133024 · Cited by 141 · see citing works
Self-citationCytochrome Oxidase Deficiency in Alzheimer's Diseasea
Parker, W. D. (1991) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1991.tb00191.x · Cited by 79 · see citing works
Deleted mitochondrial DNA in the skeletal muscle of aged individuals.
Katayama, M., Tanaka, M., Yamamoto, H., Ohbayashi, T., Nimura, Y., & Ozawa, T. (1991) · PubMed · Cited by 77 · see citing works
The neurology of aging: normal versus pathologic change.
Morris, J. G., & McManus, D. Q. (1991) · PubMed · Cited by 50 · see citing works
Deleted mitochondrial DNA in the skeletal muscle of aged individuals
片山, 信. (1992) · Medical Entomology and Zoology · doi:10.11501/3064179 · Cited by 45 · see citing works
Fukunag, M., & Yielding, K. L. (1979) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(79)91275-0 · Cited by 44 · see citing works
Report of the committee on human mitochondrial DNA
Wallace, D. C., Lott, M. T., Torroni, A., Shoffner, J. M., Chang, E., & Malik, S. (2008) · Cytogenetics and Cell Genetics · doi:10.1159/000133724 · Cited by 41 · see citing works
Self-citationPositron emission tomographic studies in aging and cerebrovascular disease at hammersmith hospital
Frackowiak, R. S. J., Wise, R. J. S., Gibbs, J. M., & Jones, T. (1984) · Annals of Neurology · doi:10.1002/ana.410150722 · Cited by 28 · see citing works
Cerebral Blood Flow and Metabolism in Aging and Dementia
Goldstein, S. J., & eivich, M. R. (1991) · Clinical Neuropharmacology · doi:10.1097/00002826-199114001-00006 · Cited by 22 · see citing works
Corral-Debrinski, M. (1991) · JAMA · doi:10.1001/jama.1991.03470130092035 · Cited by 1 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455 · see citing works
The Free Radical Theory of Aging Matures
BECKMAN, K. B., & AMES, B. N. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.2.547 · Cited by 3,879 · 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
Self-citationMitochondrial diseases in man and mouse
Wallace, D. C. (1999) · Science · doi:10.1126/science.283.5407.1482 · Cited by 3,060 · see citing works
Self-citationPremature ageing in mice expressing defective mitochondrial DNA polymerase
Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly-Y, M., Gidlöf, S., Oldfors, A., Wibom, R., et al. (2004) · Nature · doi:10.1038/nature02517 · Cited by 2,734 · see citing works
Oxidative Stress: A Key Modulator in Neurodegenerative Diseases
Singh, A., Kukreti, R., Saso, L., & Kukreti, S. (2019) · Molecules · doi:10.3390/molecules24081583 · Cited by 2,305 · see citing works
Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
Kujoth, G. C., Hiona, A., Pugh, T. D., Someya, S., Panzer, K., Wohlgemuth, S. E., Hofer, T., Seo, A. Y., Sullivan, R., Jobling, W. A., et al. (2005) · Science · doi:10.1126/science.1112125 · Cited by 2,165 · 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
Bhatti, J. S., Bhatti, G. K., & Reddy, P. H. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.11.010 · Cited by 1,655 · see citing works
Aging, 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
The role of mitochondria in aging
Bratic, A., & Larsson, N.-G. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64125 · Cited by 1,087 · 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
Ageing and Parkinson's disease: Why is advancing age the biggest risk factor?
Reeve, A. K., Simcox, E. M., & Turnbull, D. M. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.01.004 · Cited by 961 · see citing works
Kraytsberg, Y., Kudryavtseva, E., McKee, A. C., Geula, C., Kowall, N. W., & Khrapko, K. (2006) · Nature Genetics · doi:10.1038/ng1778 · Cited by 884 · see citing works
A “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease
Swerdlow, R. H., & Khan, S. M. (2004) · Medical Hypotheses · doi:10.1016/j.mehy.2003.12.045 · Cited by 758 · see citing works
Human mitochondrial DNA: roles of inherited and somatic mutations
Schon, E. A., DiMauro, S., & Hirano, M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3275 · Cited by 757 · see citing works
Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain
Mecocci, P., MacGarvey, U., Kaufman, A. E., Koontz, D., Shoffner, J. M., Wallace, D. C., & Beal, M. F. (1993) · Annals of Neurology · doi:10.1002/ana.410340416 · Cited by 757 · see citing works
Self-citationBase 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
Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity
Fromenty, B., & Pessayre, D. (1995) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(95)00012-6 · Cited by 665 · see citing works
Mitochondria-Ros Crosstalk in the Control of Cell Death and Aging
Marchi, S., Giorgi, C., Suski, J. M., Agnoletto, C., Bononi, A., Bonora, M., Marchi, E. D., Missiroli, S., Patergnani, S., Poletti, F., et al. (2011) · Journal of Signal Transduction · doi:10.1155/2012/329635 · Cited by 639 · see citing works
Mitochondrial optic neuropathies—Disease mechanisms and therapeutic strategies
Yu-Wai-Man, P., Griffiths, P. G., & Chinnery, P. F. (2011) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2010.11.002 · Cited by 633 · 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
Do defecs in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases?
Beal, M. F., Hyman, B. T., & Koroshetz, W. J. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90117-5 · Cited by 574 · see citing works
Somatic Mitochondrial DNA Mutations in Mammalian Aging
Larsson, N. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060408-093701 · Cited by 543 · see citing works
Indo, H. P., Davidson, M. M., Yen, H., Suenaga, S., Tomita, K., Nishii, T., Higuchi, M., Koga, Y., Ozawa, T., & Majima, H. J. (2006) · Mitochondrion · doi:10.1016/j.mito.2006.11.026 · Cited by 536 · see citing works
Mitochondrial 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
Self-citationMOLECULAR GENETIC ASPECTS OF HUMAN MITOCHONDRIAL DISORDERS
Larsson, N.-G., & Clayton, D. A. (1995) · Annual Review of Genetics · doi:10.1146/annurev.ge.29.120195.001055 · Cited by 493 · see citing works
Mitochondrial DNA copy number in human disease: the more the better?
Filograna, R., Mennuni, M., Alsina, D., & Larsson, N. (2020) · FEBS Letters · doi:10.1002/1873-3468.14021 · Cited by 478 · see citing works
Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases
Giorgi, C., Marchi, S., Simões, I. C. M., Ren, Z., Morciano, G., Perrone, M., Patalas‐Krawczyk, P., Borchard, S., Jędrak, P., Pierzynowska, K., et al. (2018) · International review of cytology · doi:10.1016/bs.ircmb.2018.05.006 · Cited by 467 · see citing works
Ageing as a primary risk factor for Parkinson's disease: evidence from studies of non-human primates
Collier, T. J., Kanaan, N. M., & Kordower, J. H. (2011) · Nature reviews. Neuroscience · doi:10.1038/nrn3039 · Cited by 453 · see citing works
Mitochondrial DNA damage and reactive oxygen species in neurodegenerative disease
Nissanka, N., & Moraes, C. T. (2017) · FEBS Letters · doi:10.1002/1873-3468.12956 · Cited by 453 · see citing works
DNA Damage, DNA Repair, Aging, and NeurodegenerationPreprint
Maynard, S., Fang, E. F., Scheibye‐Knudsen, M., Croteau, D. L., & Bohr, V. A. (2015) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a025130 · Cited by 439 · see citing works
Alzheimer’s disease pathogenesis and therapeutic interventions
Parihar, M. S., & Hemnani, T. (2004) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2003.12.007 · Cited by 434 · see citing works
Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs
Bacman, S. R., Williams, S. L., Pinto, M., Peralta, S., & Moraes, C. T. (2013) · Nature Medicine · doi:10.1038/nm.3261 · Cited by 432 · see citing works
Mitochondrial dysfunction in type 2 diabetes mellitus: an organ-based analysis
Pinti, M. V., Fink, G. K., Hathaway, Q. A., Durr, A. J., Kunovac, A., & Hollander, J. M. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00314.2018 · Cited by 432 · see citing works
Hudson, G., Amati-Bonneau, P., Blakely, E. L., Stewart, J. D., He, L., Schaefer, A. M., Griffiths, P. G., Ahlqvist, K., Suomalainen, A., Reynier, P., et al. (2008) · Brain · doi:10.1093/brain/awm272 · Cited by 428 · see citing works
Ono, T., Isobe, K., Nakada, K., & Hayashi, J.-I. (2001) · Nature Genetics · doi:10.1038/90116 · Cited by 420 · see citing works
Replicating Huntington's disease phenotype in experimental animals
Brouillet, E. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(99)00005-2 · Cited by 413 · see citing works
Mitochondrial dysfunction in cardiovascular disease
Ballinger, S. W. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.02.014 · Cited by 405 · see citing works
Mitochondrial allostatic load puts the 'gluc' back in glucocorticoids
Picard, M., Juster, R.-P., & McEwen, B. S. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.22 · Cited by 405 · see citing works
Troen, B. R. (2003) · PubMed · Cited by 403 · see citing works
Inflammation and Alzheimer’s disease
Lee, Y.-J., Han, S. B., Nam, S.-Y., Oh, K.-W., & Hong, J. T. (2010) · Archives of Pharmacal Research · doi:10.1007/s12272-010-1006-7 · Cited by 396 · see citing works
Commuting the death sentence: how oocytes strive to survive
Tilly, J. L. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35099086 · Cited by 392 · see citing works
Ames, 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
Bao, H., Cao, J., Chen, M., Min, C., Chen, W., Chen, X., Chen, Y., Chen, Y., Chen, Y., Chen, Z., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2305-0 · Cited by 389 · see citing works
Cassarino, D. S., & Bennett, J. P. (1999) · Brain Research Reviews · doi:10.1016/s0165-0173(98)00046-0 · Cited by 379 · see citing works
Monzio Compagnoni, G., Di Fonzo, A., Corti, S., Comi, G. P., Bresolin, N., & Masliah, E. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01926-1 · Cited by 378 · see citing works
Mitochondrial dysfunction as a cause of ageing
Trifunović, A., & Larsson, N. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01905.x · Cited by 375 · see citing works
Gabuzda, 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
Biswas, G., Adebanjo, O. A., Freedman, B. D., Anandatheerthavarada, H. K., Vijayasarathy, C., Zaidi, M., Kotlikoff, M., & Avadhani, N. G. (1999) · The EMBO Journal · doi:10.1093/emboj/18.3.522 · Cited by 369 · see citing works
High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain
Lin, M. T. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.2.133 · 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
Mitophagy in neurodegeneration and aging
Fivenson, E. M., Lautrup, S., Sun, N., Scheibye-Knudsen, M., Stevnsner, T., Nilsen, H., Bohr, V. A., & Fang, E. F. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.02.007 · Cited by 364 · 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
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
Safdar, A., Bourgeois, J. M., Ogborn, D. I., Little, J. P., Hettinga, B. P., Akhtar, M., Thompson, J. E., Melov, S., Mocellin, N. J., Kujoth, G. C., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019581108 · Cited by 358 · see citing works
RetractedOxidative 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
Mitochondrial genetic medicine
Wallace, D. C. (2018) · Nature Genetics · doi:10.1038/s41588-018-0264-z · Cited by 344 · see citing works
Self-citationA mitochondrial bioenergetic etiology of disease
Wallace, D. C. (2013) · Journal of Clinical Investigation · doi:10.1172/jci61398 · Cited by 342 · see citing works
Self-citationThe 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
Random intracellular drift explains the clonal expansion of mitochondrial DNA mutations with age
Elson, J. L., Samuels, D. C., Turnbull, D. M., & Chinnery, P. F. (2001) · The American Journal of Human Genetics · doi:10.1086/318801 · Cited by 340 · see citing works
Mitochondrial dysfunction in aging: Much progress but many unresolved questions
Payne, B. A. I., & Chinnery, P. F. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.022 · Cited by 335 · see citing works
Cui, K., Luo, X., Xu, K., & Murthy, M. R. V. (2004) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2004.05.023 · Cited by 334 · see citing works
Detection and quantification of mitochondrial DNA deletions in individual cells by real-time PCR
He, L. (2002) · Nucleic Acids Research · doi:10.1093/nar/gnf067 · Cited by 320 · see citing works
Psychological Stress and Mitochondria: A Conceptual Framework
Picard, M. A., & McEwen, B. S. (2018) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000544 · Cited by 318 · 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
“Levels of a 5-kilobase deletion that particularly affects mtDNA COX genes increase with age [115].”
BackgroundMitochondrial involvement in psychiatric disorders
Shao, L., Martin, M. V., Watson, S. J., Schatzberg, A. F., Akil, H., Myers, R., Jones, E. G., Bunney, W. E., & Vawter, M. P. (2008) · Annals of Medicine · doi:10.1080/07853890801923753 · Cited by 303 · see citing works
Mitochondrial DNA variation and cancer
Kopinski, P. K., Singh, L. N., Zhang, S., Lott, M. T., & Wallace, D. C. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00358-w · Cited by 301 · see citing works
Self-citationRoss, J. M., Öberg, J., Brené, S., Coppotelli, G., Terzioglu, M., Pernold, K., Goiny, M., Sitnikov, R., Kehr, J., Trifunovic, A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008189107 · Cited by 299 · see citing works
A mitochondrial etiology of Alzheimer and Parkinson disease
Coskun, P. E., Wyrembak, J., Schriner, S. E., Chen, H.-W., Marciniack, C., LaFerla, F. M., & Wallace, D. C. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.08.008 · Cited by 297 · see citing works
Self-citationMitochondrial 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
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
Sterky, F. H., Lee, S., Wibom, R., Olson, L., & Larsson, N. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103295108 · Cited by 296 · see citing works
Mitochondria and Reactive Oxygen Species
Addabbo, F., Montagnani, M., & Goligorsky, M. S. (2009) · Hypertension · doi:10.1161/hypertensionaha.109.130054 · Cited by 294 · see citing works
Ischemic Delayed Neuronal Death
Abe, K., Aoki, M., Kawagoe, J., Yoshida, T., Hattori, A., Kogure, K., & Itoyama, Y. (1995) · Stroke · doi:10.1161/01.str.26.8.1478 · Cited by 289 · see citing works
Are mitochondria critical in the pathogenesis of Alzheimer's disease?
Reddy, P. H., & Beal, M. F. (2005) · Brain Research Reviews · doi:10.1016/j.brainresrev.2005.03.004 · Cited by 289 · see citing works
Benzi, G., & Moretti, A. (1995) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(94)00244-e · Cited by 283 · see citing works
Brierley, E. J., Johnson, M. A., Lightowlers, R. N., James, O., & Turnbull, D. M. (1998) · Annals of Neurology · doi:10.1002/ana.410430212 · Cited by 282 · see citing works
Dai, D., Chen, T., Wanagat, J., Laflamme, M., Marcinek, D. J., Emond, M. J., Ngo, C. P., Prolla, T. A., & Rabinovitch, P. S. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00581.x · Cited by 280 · see citing works
Germline mitochondrial DNA mutations aggravate ageing and can impair brain development
Ross, J. M., Stewart, J. B., Hagström, E., Brené, S., Mourier, A., Coppotelli, G., Freyer, C., Lagouge, M., Hoffer, B. J., Olson, L., et al. (2013) · Nature · doi:10.1038/nature12474 · Cited by 273 · see citing works
Melov, S., Shoffner, J. M., Kaufman, A. E., & Wallace, D. C. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.20.4122 · Cited by 271 · see citing works
Self-citationHiona, A., Sanz, A., Kujoth, G. C., Pamplona, R., Seo, A. Y., Hofer, T., Someya, S., Miyakawa, T., Chie, N., Samhan-Arias, A. K., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011468 · Cited by 269 · see citing works
Wallace, D. C. (1995) · PubMed Central · Cited by 264 · see citing works
Self-citationAge‐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
Mitochondrial Dysfunction and Glaucoma
Kong, G. Y. X., Bergen, N. J. V., Trounce, I. A., & Crowston, J. G. (2009) · Journal of Glaucoma · doi:10.1097/ijg.0b013e318181284f · Cited by 261 · see citing works
Lee, H., Pang, C., Hsu, H., & Wei, Y. (1994) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/0925-4439(94)90056-6 · Cited by 255 · see citing works
Mitochondrial Dysfunction in Parkinson’s Disease—Cause or Consequence?
Chen, C., Turnbull, D. M., & Reeve, A. K. (2019) · Biology · doi:10.3390/biology8020038 · Cited by 253 · see citing works
HIONA, A. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2007.10.001 · Cited by 247 · see citing works
MtDNA mutations in aging and apoptosis
Chomyn, A., & Attardi, G. M. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)00625-9 · Cited by 243 · see citing works
Floyd, R. A. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00293-7 · Cited by 240 · see citing works
An autosomal locus predisposing to deletions of mitochondrial DNA
Suomalainen, A., Kaukonen, J., Amati‐Bonneau, P., Timonen, R., Haltia, M., Weissenbach, J., Zeviani, M., Somer, H., & Peltonen, L. (1995) · Nature Genetics · doi:10.1038/ng0295-146 · Cited by 238 · see citing works
Chinnery, P. F., Samuels, D. C., Elson, J. L., & Turnbull, D. M. (2002) · The Lancet · doi:10.1016/s0140-6736(02)11310-9 · Cited by 234 · see citing works
Oxidative damage to mitochondria and aging
Remmen, H. V. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00093-6 · Cited by 233 · see citing works
Payne, B. A. I., Wilson, I., Hateley, C. A., Horváth, R., Santibanez‐Koref, M., Samuels, D. C., Price, D., & Chinnery, P. F. (2011) · Nature Genetics · doi:10.1038/ng.863 · Cited by 232 · see citing works
Mitochondria in the signaling pathways that control longevity and health span
Akbari, M., Kirkwood, T. B. L., & Bohr, V. A. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100940 · Cited by 232 · see citing works
Microglial aging in the healthy CNS: phenotypes, drivers, and rejuvenation
Wong, W. T. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00022 · Cited by 227 · see citing works
Is There a Link between Mitochondrial Reserve Respiratory Capacity and Aging?
Desler, C., Hansen, T. L., Frederiksen, J. H., Espersen, M. L. M., Singh, K. K., & Rasmussen, L. J. (2012) · Journal of Aging Research · doi:10.1155/2012/192503 · Cited by 225 · see citing works
Mitochondrial DNA mutations in human degenerative diseases and aging
Wallace, D. C., Shoffner, J. M., Trounce, I. A., Brown, M. D., Ballinger, S. W., Corral‐Debrinski, M., Horton, T. M., Jun, A. S., & Lott, M. T. (1995) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/0925-4439(95)00021-u · Cited by 225 · see citing works
Self-citationDamage, Repair, and Mutagenesis in Nuclear Genes after Mouse Forebrain Ischemia–Reperfusion
Liu, P. K., Hsu, C. Y., Dizdaroğlu, M., Floyd, R. A., Kow, Y. W., Karakaya, A., Rabow, L. E., & Cui, J.-K. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-21-06795.1996 · Cited by 224 · see citing works
Oxidative Stress and Motor Neurone Disease
Cookson, M., & Shaw, P. J. (1999) · Brain Pathology · doi:10.1111/j.1750-3639.1999.tb00217.x · Cited by 223 · see citing works
- Authors
- Corral-Debrinski, M., Horton, T., Lott, M. T., Shoffner, J. M., Flint Beal, M., & Wallace, D. C.
- Affiliations
- Emory University (US)
- Venue
- Nature Genetics
- Published
- 1992-12
- Volume
- 2
- Issue
- 4
- Pages
- 324-329
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1973851166
- Cited by
- 890
- References
- 43
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 19 · 2023: 12 · 2022: 25 · 2021: 19 · 2020: 23 · 2019: 36 · 2018: 21 · 2017: 28 · 2016: 21 · 2015: 32 · 2014: 23 · 2013: 32 · 2012: 24
- FWCI
- 10.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- 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
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- mitochondrial DNA deletions, somatic mtDNA mutations, human aging, brain aging, cerebral cortex, putamen, cerebellum, regional variation, neurological deficit
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Base Sequence, Brain, DNA Damage, DNA, Mitochondrial, Female, Humans, Male, Molecular Sequence Data, Oxidative Phosphorylation, Tissue Distribution, Sequence Deletion
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