Cited by 757Mitochondrial Function and PathologyGenetics, Aging, and Longevity in Model OrganismsDNA Repair Mechanisms

The DOI matches its Crossref record; 49 of the 50 references it cites were found in a registry or an index.

Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain

Mecocci, Patrizia, MacGarvey, Usha, Kaufman, Allan E., Koontz, Deborah, Shoffner, John M., Wallace, Douglas C., Beal, M. Flint·1993·Annals of Neurology

DOI 10.1002/ana.410340416

Open this paper in CoChat — free account

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

Crossref · 10.1002/ana.410340416

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
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
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
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
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
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
Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported
Evans, D. A. (1989) · JAMA · doi:10.1001/jama.262.18.2551 · Cited by 1,627
Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNALys mutation
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 1,476
Mitochondrial Genetics: A Paradigm for Aging and Degenerative Diseases?
Wallace, D. C. (1992) · Science · doi:10.1126/science.1533953 · Cited by 1,262
Prevalence of Alzheimer's Disease in a Community Population of Older Persons: Higher Than Previously Reported
Evans, D. A. (1989) · JAMA · doi:10.1001/jama.1989.03430180093036 · Cited by 1,226
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

Show all 50 references

Research works printed but not linked: 2

Nohl H, 1986, Free radicals, aging, and degenerative disease, 77
DiMonte DA, 1992, Age‐related changes in mitochondrial energy metabolism in the squirrel monkey, Soc Neurosci Abstr, 18, 1488

Sorted by citations

Items 501–600 of 756

Role of free radical and antioxidant imbalance in pathogenesis of Parkinson's disease.
Nikam, S., Nikam, P., & Ahaley, S. K. (2009) · Cited by 20
Experimental Models of HD and Reflection on Therapeutic Strategies
Kim, J., Bordiuk, O. L., & Ferrante, R. J. (2011) · International review of neurobiology · doi:10.1016/b978-0-12-381328-2.00016-x · Cited by 20
UV-irradiation induces oxidative damage to mitochondrial DNA primarily through hydrogen peroxide: Analysis of 8-oxodGuo by HPLC
Takai, D., Park, S., Takada, Y., Ichinose, S., Kitagawa, M., & Akashi, M. (2006) · Free Radical Research · doi:10.1080/10715760600838381 · Cited by 19
“Mitochondrial structures are continuously exposed to high concentrations of ROS, and studies have found mutations of mtDNA in various organs such as skeletal muscle and the central nervous system [30,31].”
Background
Immunolocalisation pattern of complex I–V in ageing human retina: Correlation with mitochondrial ultrastructure
Nag, T. C., & Wadhwa, S. (2016) · Mitochondrion · doi:10.1016/j.mito.2016.08.016 · Cited by 19
Neuronal NOS Inhibitor That Reduces Oxidative DNA Lesions and Neuronal Sensitivity Increases the Expression of Intact c-fos Transcripts after Brain Injury
Cui, J., & Liu, P. K. (2001) · Journal of Biomedical Science · doi:10.1007/bf02258375 · Cited by 19
Cardiac Involvement in Mitochondrial Diseases, and Vice Versa
Williams, R. S. (1995) · Circulation · doi:10.1161/01.cir.91.4.1266 · Cited by 19
Biomolecular Modifications Linked to Oxidative Stress in Amyotrophic Lateral Sclerosis: Determining Promising Biomarkers Related to Oxidative Stress
Hosaka, T., Tsuji, H., & Tamaoka, A. (2021) · Processes · doi:10.3390/pr9091667 · Cited by 20
Effect of dietary antioxidants on free radical damage in dogs and cats
Jewell, D. E., Motsinger, L. A., & Paetau‐Robinson, I. (2024) · Journal of Animal Science · doi:10.1093/jas/skae153 · Cited by 18
“In fact, when brain tissue from humans aged 42 to 97 yr was tested for the oxidized nucleoside 8-hydroxy-2 ʹ - deoxyguanosine, a 10-fold increase in 8-hydroxy-2 ʹ -deoxyguanosine was found in mtDNA as compared to nuclear DNA (Mecocci et al., 1993).”
BackgroundMethod
Mitochondrial DNA damage is sensitive to exogenous H2O2 but independent of cellular ROS production in prostate cancer cells
Chan, S. W., Nguyen, P.-N., Ayele, D., Chevalier, S., Aprikian, A. G., & Chen, J. Z. (2011) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2011.07.019 · Cited by 17
Recognition and Control of the Progression of Age-Related Hearing Loss
Ren, H., Ren, J., & Liu, W. (2013) · Rejuvenation Research · doi:10.1089/rej.2013.1435 · Cited by 18
“Normal metabolism causes ROS production by the electron transport chain; subsequently, ROS, which are generated inside the mitochondria, damage lipids, proteins,(19) and the nucleic acids in mitochondria.(20) As a result, the ROSinduced mtDNA mutations lead to the synthesis of functionally impaired respiratory chain s…”
Background
Calorie Restriction and Dwarf Mice in Gerontological Research
Alderman, J. M., DePetrillo, M. A., Gluesenkamp, A. M., Hartley, A. C., Verhoff, S. V., Zavodni, K. L., & Combs, T. P. (2009) · Gerontology · doi:10.1159/000235720 · Cited by 18
“Snell and Ames dwarf mice share multiple characteristics with mice on CR including reduced food intake. Mice on CR consume less food per day than ad libitum fed mice because less is available to them; Snell and Ames dwarf mice consume less food per day voluntarily. This implies that increased appetite and dramatic met…”
Background
Chronic Mitochondrial Inhibition Induces Glutamate-Mediated Corticomotoneuron Death in an Organotypic Culture Model
van Westerlaak, M. G. H., Joosten, E. A. J., Gribnau, A. A. M., Cools, A. R., & Bär, P. R. (2001) · Experimental Neurology · doi:10.1006/exnr.2000.7570 · Cited by 18
Mapping the future of oxidative RNA damage in neurodegeneration: Rethinking the status quo with new tools
Wheeler, H. B., Madrigal, A. A., & Chaim, I. A. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2317860121 · Cited by 18
“Many groundbreaking studies have utilized postmortem samples to characterize terminal disease patho logy in ALS (31, 32), AD (27, 28), and PD (30, 52).”
Cypermethrin alters the status of oxidative stress in the peripheral blood: relevance to Parkinsonism
Tripathi, P., Singh, A. K., Agrawal, S., Prakash, O., & Singh, M. P. (2014) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-014-0359-7 · Cited by 17
FGF-18 alleviates memory impairments and neuropathological changes in a rat model of Alzheimer's disease
ÇİLTAŞ, A. Ç., Karabulut, S., Şahin, B., Filiz, A. K., Yulak, F., Özkaraca, M., Karataş, Ö., & Cetin, A. (2023) · Neuropeptides · doi:10.1016/j.npep.2023.102367 · Cited by 16
Restricción calórica, estrés oxidativo y longevidad
Lopez‐Torres, M., & Barja, G. (2008) · Revista Española de Geriatría y Gerontología · doi:10.1016/s0211-139x(08)71190-9 · Cited by 16
Plasma oxidized low-density lipoprotein levels and risk of Alzheimer's disease
Murr, J., Carmichael, P., Julien, P., & Laurin, D. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.02.007 · Cited by 17
“In parallel to these processes, increased regional levels of oxidative stress (Markesbery, 1997; Zhu et al., 2005) and evidence of oxidative damage, mainly oxidized lipids, proteins (Smith et al., 1995), and nucleic acids (Mecocci et al., 1993), can be found in neurodegenerative disorders.”
Background
Analysis of the Effects of Ninjin’yoeito on Physical Frailty in Mice
Otsuka, S., Fukumaru, K., Tani, A., Takada, S., Kikuchi, K., Norimatsu, K., Matsuzaki, R., Matsuoka, T., Sakakima, H., Omiya, Y., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911183 · Cited by 16
“A previous study revealed elevated levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of nucleic acid oxidation, in circulating lymphocyte DNA from patients with Alzheimer’s disease [21,22].”
Background
Reductive Reprogramming: A Not-So-Radical Hypothesis of Neurodegeneration Linking Redox Perturbations to Neuroinflammation and Excitotoxicity
Foley, T. D. (2019) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-019-00672-w · Cited by 16
RETRACTED ARTICLE: Molecular Mechanisms of Aging: The Role of Oxidative Stress and Epigenetic Modifications
Айтбаев, К. А., Murkamilov, I. T., & Fomin, V. V. (2019) · Advances in Gerontology · doi:10.1134/s2079057019040027 · Cited by 16
Retracted
Paucity of deleted mitochondrial DNAs in brain regions of Huntington's disease patients
Chen, X., Bonilla, E., Sciacco, M., & Schon, E. A. (1995) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/0925-4439(95)00032-y · Cited by 16
Whole-body metabolic rate appears to determine the rate of DNA oxidative damage and glycation involved in aging
Greenberg, J. A., Wei, H., Ward, K. M., & Boozer, C. N. (2000) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00108-1 · Cited by 16
Excitotoxicity in the Brain
Fonnum, F. (1998) · Archives of toxicology. Supplement · doi:10.1007/978-3-642-46856-8_34 · Cited by 16
Role of Oxidative DNA Damage and Antioxidative Enzymatic Defence Systems in Human Aging~!2008-08-08~!2008-10-29~!2008-12-05~!
Dittmar, M., Knuth, M., Beineke, M., & Epe, B. (2008) · The Open Anthropology Journal · doi:10.2174/1874912700801010038 · Cited by 15
Free radical processes in aging, neurodegenerative diseases and other pathological states
Dubinina, E. E., & Васильевна, П. А. (2007) · Biochemistry (Moscow) Supplement Series B Biomedical Chemistry · doi:10.1134/s1990750807040026 · Cited by 15
Mitochondrial Gene Therapy: An Evaluation of Strategies for the Treatment of Mitochondrial DNA Disorders
Doyle, S. R., & Chan, C. K. (2008) · Human Gene Therapy · doi:10.1089/hum.2008.090 · Cited by 15
Analysis of age-associated mitochondrial DNA deletion breakpoint regions from mice suggests a novel model of deletion formation
Chung, S. S., Eimon, P. M., Weindruch, R. H., & Aiken, J. M. (1996) · AGE · doi:10.1007/bf02434081 · Cited by 15
A unifying hypothesis of Alzheimer's disease. I. Ageing sets the stage
Heininger, K. (1999) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/(sici)1099-1077(199908)14:6 · Cited by 15
Topographical localization of lipofuscin pigment in the brain of the aged fat-tailed dwarf lemur(Cheirogaleus Medius) and grey lesser mouse lemur(Microcebus Murinus): Comparison to iron localization
Gilissen, E., Jacobs, R. E., McGuinness, E. R., & Allman, J. M. (1999) · American Journal of Primatology · doi:10.1002/(sici)1098-2345(199910)49:2 · Cited by 15
PARP-1 activation leads to cytosolic accumulation of TDP-43 in neurons
Marcus, J. M., Hossain, M. I., Gagné, J., Poirier, G. G., McMahon, L. L., Cowell, R. M., & Andrabi, S. A. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.105077 · Cited by 14
The Role of Aging in Alzheimer’s Disease
Kerchner, G. A., & Wyss‐Coray, T. (2015) · Springer eBooks · doi:10.1007/978-3-319-23246-1_7 · Cited by 14
Examination of the Taxonomy and Diversification of Leontopithecus using the Mitochondrial Control Region
Perez‐Sweeney, B., Valladares‐Pádua, C., Martins, C. S., Morales, J. C., & Melnick, D. J. (2008) · International Journal of Primatology · doi:10.1007/s10764-007-9224-7 · Cited by 14
“Therefore, we isolated mitochondria from tissue of Leontopithecus chrysomelas, Callithrix jacchus, and Saguinus oedipus, and subjected the organelle isolates to DNase to eliminate extraneous nuclear DNA from each sample (Mecocci et al. 1993).”
Method
Environmental Influences that May Precede Fertilization: A First Examination of the Prezygotic Hypothesis from Maternal Age Influences on Twins
Finch, C., & Loehlin, J. (1998) · Behavior Genetics · doi:10.1023/a:1021415823234 · Cited by 14
Striatal Dopamine Dynamics Are Altered Following an Intranigral Infusion of Iron in Adult Rats
Lin, A. M. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(97)00398-5 · Cited by 14
Oxidants and Mitochondrial Decay in Aging
Shigenaga, M. K., & Ames, B. N. (1994) · Elsevier eBooks · doi:10.1016/b978-0-08-057168-3.50009-6 · Cited by 14
Arsenite induces oxidative injury in rat brain
Fan, S., Chao, P., & Lin, A. M. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05170.x · Cited by 13
Oxidative stress in the human fetal brain: an immunohistochemical study
Yamamoto, T., Shibata, N., Muramatsu, F., Sakayori, N., & Kobayashi, M. (2002) · Pediatric Neurology · doi:10.1016/s0887-8994(01)00369-1 · Cited by 13
mRNA isoform balance in neuronal development and disease
LaForce, G. R., Philippidou, P., & Schaffer, A. E. (2022) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1762 · Cited by 15
“Together, these findings suggest that decreased efficiency of genome maintenance may increase the susceptibility of highly transcriptionally active loci to DNA damage by oxidation and contribute to the loss of synaptic plasticity, cognition, and memory in the aging brain (Colantuoni et al., 2011; Loerch et al., 2008;…”
Background
Mitochondrial dysfunction in diabetes mellitus
Anderson, C. M. (1999) · Drug Development Research · doi:10.1002/(sici)1098-2299(199901)46:1 · Cited by 18
Age-dependent Expression of 8-hydroxy-2'-deoxyguanosine in Human Pituitary Gland
Kondo, T., Ohshima, T., & Ishida, Y. (2001) · The Histochemical Journal · doi:10.1023/a:1016354417834 · Cited by 13
“Lodovici et al. (2000) measured 8-OHdG levels in human leukocytes from healthy donors to evaluate oxidative DNA damage and observed a correlation between 8-OHdG levels and age in non-smokers and former smokers (18–64 years old, n = 40). Mecocci et al. (1993) described extensive”
Background
Mitochondrial DNA Mutations in Aging
Nagley, P., & Zhang, C. (1998) · Springer eBooks · doi:10.1007/978-3-662-12509-0_11 · Cited by 13
The role of aging and brain‐derived neurotrophic factor signaling in expression of base excision repair genes in the human brain
Lautrup, S., Holst, C. M., Yde, A., Asmussen, S. E., Thinggaard, V., Larsen, K., Laursen, L. S., Richner, M., Vægter, C. B., Prieto, G. A., et al. (2023) · Aging Cell · doi:10.1111/acel.13905 · Cited by 11
Nutritional approaches targeting mitochondria for the prevention of sarcopenia
Hahm, J., Nirmala, F. S., Ha, T. Y., & Ahn, J. (2023) · Nutrition Reviews · doi:10.1093/nutrit/nuad084 · Cited by 13
Neurotoxicity of methamphetamine and methylenedioxymethamphetamine
Seiden, L. S., Lew, R., & Malberg, J. E. (2001) · Neurotoxicity Research · doi:10.1007/bf03033233 · Cited by 12
The Role of Oxidative Processes and Metal Ions in Aging and Alzheimer’s Disease
Shinobu, L. A., & Beal, M. F. (1997) · Springer eBooks · doi:10.1007/978-1-4899-0197-2_13 · Cited by 12
Effects of Dityrosine on Lactic Acid Metabolism in Mice Gastrocnemius Muscle During Endurance Exercise via the Oxidative Stress-Induced Mitochondria Damage
Xia, Q., Lan, J., Pan, Y., Wang, Y., Song, T., Yang, Y., Tian, X., Chen, L., Gu, Z., & Ding, Y. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c09649 · Cited by 11
Frequency of duplications in the D-loop in patients with mitochondrial DNA deletions
Tengan, C. H., Ferreiro-Barros, C. C., Cardeal, M., Fireman, M. A. T., Oliveira, A. S. B., Kiyomoto, B. H., & Gabbai, A. A. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(02)00140-0 · Cited by 11
A comparative study on oxidative stress and antioxidant status in ischemic stroke patients with and without diabetes
D’Souza, B., D’Souza, V., Sowmya, S. D., Seema, G., Hemalatha, C. N., Anu, M., & Sajana, G. (2008) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-008-0049-8 · Cited by 12
“Experimental studies provide evidence of an association between ischemic stroke and increased oxidative stress, but data in humans are still limited and controversial . We have particularly studied the products of lipid peroxidation since the brain is very rich in polyunsaturated fatty acids which are highly susceptib…”
Background
Mitochondrial DNA Deletions
Gadaleta, M. N., Lezza, A. M. S., & Cantatore, P. (1998) · CRC Press eBooks · doi:10.1201/b14256-27 · Cited by 11
Oxidative status--age- and circadian variations?--a study in leukocytes/plasma.
Larssen, K. S., & Lyberg, T. (2006) · PubMed · Cited by 11
Neuroanatomical mapping of DNA repair and antioxidative responses in mouse brain: Effects of a single dose of MPTP
Sava, V. M., Reunova, O., Velasquez, A., Song, S., & Sanchez‐Ramos, J. (2006) · NeuroToxicology · doi:10.1016/j.neuro.2006.05.023 · Cited by 11
Molecular and Biologic Factors in Aging: The Origins, Causes, and Prevention of Senescence
Baker, G. T., & Martin, G. R. (1997) · Springer eBooks · doi:10.1007/978-1-4757-2705-0_1 · Cited by 11
Biological Aging and Longevity: Underlying Mechanisms and Potential Intervention Strategies
Baker, G. T., & Martin, G. R. (1994) · Journal of Aging and Physical Activity · doi:10.1123/japa.2.4.304 · Cited by 10
Chapter 6 Contribution of Mitochondrial Alterations to Brain Aging
Benzi, G., & Moretti, A. (1997) · Advances in cell aging and gerontology · doi:10.1016/s1566-3124(08)60056-5 · Cited by 11
Mitochondrial DNA oxidation and content in different metabolic phenotypes of women with polycystic ovary syndrome
Rojo, M., Pérez, H., Millán, A., Pautasso, M. C., Duarte, A., Abruzzese, G., Motta, A., Frechtel, G., & Cerrone, G. E. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1501306 · Cited by 13
Human neuronal cells: epigenetic aspects
Kukucka, J., Wyllie, T., Read, J. L., Mahoney, L., & Suphioglu, C. (2013) · BioMolecular Concepts · doi:10.1515/bmc-2012-0053 · Cited by 10
“Epigenetic alterations of gene expression in the aging brain arise from DNA damage and a variety of neuronal insults, which are highly implicated during neurodegenerative maladies (20, 21) .”
Heavy metal exposure, in combination with physical activity and aging, is related with oxidative stress in Japanese women from a rural agricultural community
Cui, X., Ohtsu, M., Mise, N., Ikegami, A., Mizuno, A., Sakamoto, T., Ogawa, M., Machida, M., & Kayama, F. (2016) · SpringerPlus · doi:10.1186/s40064-016-2430-z · Cited by 10
Genetic Editing and Pharmacogenetics in Current And Future Therapy Of Neurocognitive Disorders
Prendecki, M., Kowalska, M., Totoń, E., & Kozubski, W. P. (2020) · Current Alzheimer Research · doi:10.2174/1567205017666200422152440 · Cited by 10
The Role of Oxidative Damage to Nucleic Acids in the Pathogenesis of Neurological Disease
Reddy, V. P., Beyaz, A., Perry, G. L., Cooke, M. S., Sayre, L. M., & Smith, M. A. (2007) · Springer eBooks · doi:10.1007/978-0-387-72974-9_10 · Cited by 10
Area-Specific Differences in OH8dG and mtDNA4977 Levels in Alzheimer Disease Patients and Aged Controls
Lezza, A. M. S., Mecocci, P., Cormio, A., Beal, M. F., Cherubini, A., Cantatore, P., Senin, U., & Gadaleta, M. N. (1999) · Rejuvenation Research · doi:10.1089/rej.1.1999.2.209 · Cited by 10
Contribution of de novo point mutations to the overall mutational burden in mitochondrial DNA of adult rats
Khaidakov, M., CHAVANNESTURESKY, N., Cooney, C. A., Dupont‐Versteegden, E. E., KENNEDY, R., Siegel, E. R., Khaidakova, G., & Reis, R. J. S. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.02.007 · Cited by 10
“By virtue of its close proximity to the ETS machinery and its asymmetric replication mechanism, mitochondrial DNA may be subjected to considerably higher oxidative damage (Richter et al., 1988; Mecocci et al., 1993) repaired less efficiently than similar lesions in the nuclear DNA (Croteau et al.”
Background
Oxidative Stress in Alzheimer’s Disease
Ceballos-Picot, I. (1997) · Neuroscience intelligence unit · doi:10.1007/978-3-662-22516-5_5 · Cited by 10
Association of 8-hydroxy-2’-deoxyguanosine with motoric cognitive risk in elderly Chinese people: RUGAO longevity and aging cross-sectional study
Dai, Q., Ma, Y., Liu, C., Zhao, R., Chen, Q., Chen, W., Wang, X., Jiang, X., & Li, S. (2024) · BMC Geriatrics · doi:10.1186/s12877-024-04943-0 · Cited by 9
“In 1993 [23], 8-OHdG was first measured in three regions where an age group from 42 to 97 with cerebral cortex and cerebellum was screened.”
Background
White matter lipid alterations during aging in the rhesus monkey brain
Dimovasili, C., Vitantonio, A. T., Conner, B., Vaughan, K. L., Mattison, J. A., & Rosene, D. L. (2024) · GeroScience · doi:10.1007/s11357-024-01353-3 · Cited by 9
“Although we also found reduction in the expression of catalase, it is important to note that the reduction in antioxidant expression may contribute to oxidative damage to other macromolecules, like DNA or protein [76–78], contributing to global cellular dysfunction.”
Oxygen Concentration and Oxidative Stress Modulate the Influence of Alzheimer’s Disease Aβ1–42 Peptide on Human Cells
Bender, T., & Dencher, N. A. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/7567959 · Cited by 9
“, the respiratory chain) and is less protected by stabilizing proteins and therefore is highly susceptible to oxidative damage which accumulates with aging of, for example, the human brain [2] and leads to alterations expressed in Alzheimer’s disease (AD) too [3, 4].”
Background
Melatonin, Oxidative Stress, and the Aging Brain
Bondy, S. B. C., & Sharman, E. H. (2010) · Humana Press eBooks · doi:10.1007/978-1-60761-602-3_17 · Cited by 9
“Consequently, the degree of DNA damage in aging humans is 10 times greater in the mitochondria than in the nucleus [35].”
The two faces of DNA oxidation in genomic and functional mosaicism during aging in human neurons
Lodato, M. A., & Ziegenfuss, J. S. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.991460 · Cited by 9
“In the human brain, HPLC analysis showed a progressive age-related accumulation of 8-oxoG in DNA in both the cerebellum and cortex (Mecocci et al., 1993).”
Background
Down‐regulation of apurinic/apyrimidinic endonuclease 1 ( APE 1) in spinal motor neurones under oxidative stress
Chu, T., Guo, A., & Wu, W. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12071 · Cited by 9
Neuronal injury from cardiac arrest: aging years in minutes
Cherry, B., Sumien, N., & Mallet, R. T. (2014) · AGE · doi:10.1007/s11357-014-9680-x · Cited by 9
“…close proximity to the respiratory chain, the mitochondrial genome is particularly susceptible to oxidative damage from excessive ROS/ RNS produced during ischemia-reperfusion (Richter 1995; Chen et al. 2001) and accumulated during aging (Mecocci et al. 1993; Ozawa 1995; Barja and Herrero 2000).”
Background
Mitochondrial disorders in degenerative ataxias
Schöls, L. J., Reichmann, H., Amoiridis, G., Seibel, P., Wagener, S., Seufert, S., & Przuntek, H. (1996) · European Journal of Neurology · doi:10.1111/j.1468-1331.1996.tb00190.x · Cited by 9
An Overview of the Molecular and Cellular Biomarkers of Aging
Solovev, I. A., Shaposhnikov, M. V., & Moskalev, A. (2019) · Healthy ageing and longevity · doi:10.1007/978-3-030-24970-0_6 · Cited by 9
Investigation of mitochondrial involvement in the experimental model of epilepsy induced by pilocarpine
Nasseh, I. E., Amado, D., Cavalheiro, É. A., Naffah‐Mazzacoratti, M. D. G., & Tengan, C. H. (2005) · Epilepsy Research · doi:10.1016/j.eplepsyres.2005.11.009 · Cited by 9
NF-κB activity decreases in basal forebrain of young and aged rats after hyperoxia
Toliver-Kinsky, T. E., Rassin, D. K., & Perez-Polo, J. R. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00023-4 · Cited by 9
“This hypothesis is supported by reports of aging-associated increases in the levels of lipid peroxidation products [39,57], oxidized proteins [21,26,54], oxidative DNA damage and repair [14,19,38], and levels of reactive oxygen species (ROS) [18], together with decreases in antioxidant levels in brain extracts and/or…”
Background
Multisession anodal epidural direct current stimulation of the auditory cortex delays the progression of presbycusis in the Wistar rat
del Campo, I. S. F., Carmona-Barrón, V. G., Díaz, I. D. P., Plaza, I., Alvarado, J. C., & Merchán, M. Á. (2024) · Hearing Research · doi:10.1016/j.heares.2024.108969 · Cited by 8
“Currently, activity-dependent reactive oxygen species (ROS) accumulation and a weakened antioxidant defense are known to induce cell damage through oxidative imbalances and mitochondrial DNA in aging (Asuncion et al., 1996; Mecocci et al., 1993; Shigenaga et al., 1994; Wallace, 2001).”
Background
Inhibitory Effects of Dropwort (Oenanthe javanica) Extracts on Memory Impairment and Oxidative Stress and the Qualitative Analysis of Isorhamnetin in the Extracts
Won, B. Y., Shin, K. Y., Ha, H. J., Wee, J., Yun, Y. S., Kim, Y. R., Park, Y. J., Jung, K. O., Sung, H. M., & Lee, H. G. (2016) · Journal of the Korean Society of Food Science and Nutrition · doi:10.3746/jkfn.2016.45.1.001 · Cited by 8
“또한 인지장애를 일으키는 손상 부위인 뇌 신 경세포는 다른 조직에 비해 고도 불포화지방산 함량과 산소 소비가 높은 반면, 항산화 효소는 상대적으로 부족하여 산화 적 스트레스에 의한 영향이 크다(5,6).”
Polyglucosan Bodies in Aged Brain and Neurodegeneration: Cause or Consequence?
Rai, A., & Ganesh, S. (2019) · Springer eBooks · doi:10.1007/978-981-13-3585-3_4 · Cited by 8
Oxidative Stress-Induced Cell Damage in the CNS
Robb-Gaspers, S. J., & Connor, J. R. (1997) · Springer eBooks · doi:10.1007/978-1-4899-0197-2_18 · Cited by 8
Visual Defects and Ageing
Saccà, S. C., Cutolo, C. A., & Rossi, T. (2019) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-3681-2_14 · Cited by 8
Final report (revised)
Paramasivam, R. (2001) · Cited by 8
Molecular analysis of mitochondrial DNA mutations from bleomycin-treated rats
Khaidakov, M., Manjanatha, M. G., & Aidoo, A. (2002) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(01)00270-6 · Cited by 8
Future research in Alzheimer's disease using imaging techniques
Budinger, T. F. (1994) · Neurobiology of Aging · doi:10.1016/0197-4580(94)90166-x · Cited by 8
Mitochondrial DNA deletions are rare in the free radical-rich retinal environment
Soong, N.-W., Dang, M. H., Hinton, D. R., & Arnheim, N. (1996) · Neurobiology of Aging · doi:10.1016/s0197-4580(96)00163-7 · Cited by 8
Long-range PCR as a tool for evaluating mitochondrial DNA damage: Principles, benefits, and limitations of the technique
Gureev, A. P., Nesterova, V. V., & Sadovnikova, I. S. (2025) · DNA repair · doi:10.1016/j.dnarep.2025.103812 · Cited by 7
Protein Transduction Domain-Mediated Delivery of Recombinant Proteins and In Vitro Transcribed mRNAs for Protein Replacement Therapy of Human Severe Genetic Mitochondrial Disorders: The Case of Sco2 Deficiency
Miliotou, Α. N., Foltopoulou, P. F., Ingendoh‐Tsakmakidis, A., Tsiftsoglou, A. S., Vizirianakis, I. S., Pappas, I. S., & Papadopoulou, L. C. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15010286 · Cited by 7
“The lack of protective histones and limited repair mechanisms make the mitochondrial genome highly susceptible to oxidative damage [30,31], with an estimated mutation rate 10–20 times higher than that of nDNA [32].”
Background
D609-mediated inhibition of ATP synthesis in neural progenitor cells
Kalluri, H. S. G., & Dempsey, R. J. (2014) · Neuroreport · doi:10.1097/wnr.0000000000000176 · Cited by 7
Mediterranean Diet and Longevity
Matalas, A.-L., Zampelas, A., & Stavrinos, V. (2001) · CRC Press eBooks · doi:10.1201/9781420042221-12 · Cited by 7
Mecanismos moleculares do envelhecimento: revisão da literatura
d’Avila, J. C., Ramos, A. C. B., Dourado, D. R. D. S., Siqueira, R. D. A., Carlos, A. S., & Moreno, A. M. (2020) · Revista Brasileira de Ciências do Envelhecimento Humano · doi:10.5335/rbceh.v17i1.10543 · Cited by 10
Mitochondrial Medicine
Wallace, D. C., Lott, M. T., & Procaccio, V. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-383834-6.00013-6 · Cited by 8
Mechanisms of DNA Damage and Repair in Alzheimer Disease
Reddy, V. P., Perry, G. L., Cooke, M. S., Sayre, L. M., & Smith, M. A. (2006) · Springer eBooks · doi:10.1007/0-387-36802-7_8 · Cited by 7
Serum level of melatonin in patients with osteoarthritis and its relation with 8-hydroxy-2-deoxyguanosine and vitamin D
Oskoii, M. A., Khatami, N., Majidinia, M., Rezazadeh, M., Mir, S. M., Sadeghpour, A., & Yousefi, B. (2020) · Journal of Research in Clinical Medicine · doi:10.34172/jrcm.2020.034 · Cited by 7
Chapter 5 Metabolism of the Aging Brain
Blass, J. P., Gibson, G. E., & Hoyer, S. (1997) · Advances in cell aging and gerontology · doi:10.1016/s1566-3124(08)60055-3 · Cited by 7
The In Situ Detection of Apurinic/Apyrimidinic Sites and DNA Breaks Bearing Extension Blocking Termini
Liu, P. K., Cui, J., Moore, N., & Huang, D. (2003) · Humana Press eBooks · doi:10.1385/1-59259-179-5:235 · Cited by 7
Free Radicals and Mammalian Aging
Sanz, A., Barja, G., Pamplona, R., & Leeuwenburgh, C. (2009) · Wiley eBooks · doi:10.1002/9783527627585.ch19 · Cited by 8
Mitochondrial DNA Instability and Neuroinflammation: Connecting the Dots Between Base Excision Repair and Neurodegenerative Disease
Pittman, M. N., Nelsen, M. B., Thompson, M. K., & Prakash, A. (2026) · Genes · doi:10.3390/genes17010082 · Cited by 6
“In contrast to these inherited disorders, mtDNA damage most relevant to aging and neurodegeneration, especially those affecting post-mitotic neurons, is accumulated gradually over a lifetime [4,78–80].”
Expression of 8-oxoguanine DNA glycosylase (Ogg1) in mouse retina.
Bigot, K., Leemput, J., Vacher, M., Campalans, A., Radicella, J. P., Lacassagne, E., Provost, A. C., Masson, C., Ménasche, M., & Abitbol, M. M. (2009) · PubMed Central · Cited by 6
The association between mitochondrial DNA copy number, telomere length, and tubal pregnancy
Huang, Z., Zhao, X., Zhang, H., Liang, G., Qi, H., He, X., Zhu, C., Ge, S., & Zhang, J. (2020) · Placenta · doi:10.1016/j.placenta.2020.06.017 · Cited by 6
Molekulare Medizin der Alzheimer-Krankheit
Hoyer, S., Frölich, L., & Sandbrink, R. (1999) · Springer eBooks · doi:10.1007/978-3-662-07096-3_7 · Cited by 6
Aging and the Accumulation of Oxidative Damage to DNA
Takao, K. (2004) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.34.51 · Cited by 6
Redox Enzymes
Dykens, J. A. (2007) · Elsevier eBooks · doi:10.1016/b0-08-045044-x/00071-7 · Cited by 6
Increased Oxidative Damage in RNA in Alzheimer’s Disease Progression
Lovell, W. M. (2014) · Journal of Analytical & Bioanalytical Techniques · doi:10.4172/2155-9872.s2-004 · Cited by 5

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
ORCID: Mecocci, Patrizia
Shoffner, John M.
Wallace, Douglas C.
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
DOI: 10.1002/ana.410340416
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 4025 d)
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

Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks