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Licensed Unlicensed Requires Authentication Published by De Gruyter August 25, 2014

Oxidative stress and genetic markers of suboptimal antioxidant defense in the aging brain: a theoretical review

  • Lauren E. Salminen

    Lauren Salminen is a doctoral student in the Behavioral Neuroscience program at the University of Missouri – St. Louis. Her research is predominantly focused on genetic and vascular markers of suboptimal brain health in older individuals.

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    and Robert H. Paul

    Robert Paul is a board certified clinical neuropsychologist and director of the Missouri Institute of Mental Health located in St. Louis, Missouri. Dr. Paul’s research is focused on the neuropsychology of subcortical ischemic vascular disease associated with advanced age and human immunodeficiency virus (HIV). Dr. Paul has maintained a federally-funded grant program since 1991 and has published more than 200 scientific articles in peer-reviewed journals.


Normal aging involves a gradual breakdown of physiological processes that leads to a decline in cognitive functions and brain integrity, yet the onset and progression of decline are variable among older individuals. While many biological changes may contribute to this degree of variability, oxidative stress is a key mechanism of the aging process that can cause direct damage to cellular architecture within the brain. Oligodendrocytes are at a high risk for oxidative damage due to their role in myelin maintenance and production and limited repair mechanisms, suggesting that white matter may be particularly vulnerable to oxidative activity. Antioxidant defense enzymes within the brain, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST), are crucial for breaking down the harmful end products of oxidative phosphorylation. Previous studies have revealed that allele variations of polymorphisms that encode these antioxidants are associated with abnormalities in SOD, CAT, GPx, and GST activity in the central nervous system. This review will focus on the role of oxidative stress in the aging brain and the impact of decreased antioxidant defense on brain integrity and cognitive function. Directions for future research investigations of antioxidant defense genes will also be discussed.

Corresponding author: Lauren E. Salminen, Department of Psychology, University of Missouri- Saint Louis, 1 University Boulevard, Stadler Hall 442 A, St. Louis, MO 63121, USA, e-mail:

About the authors

Lauren E. Salminen

Lauren Salminen is a doctoral student in the Behavioral Neuroscience program at the University of Missouri – St. Louis. Her research is predominantly focused on genetic and vascular markers of suboptimal brain health in older individuals.

Robert H. Paul

Robert Paul is a board certified clinical neuropsychologist and director of the Missouri Institute of Mental Health located in St. Louis, Missouri. Dr. Paul’s research is focused on the neuropsychology of subcortical ischemic vascular disease associated with advanced age and human immunodeficiency virus (HIV). Dr. Paul has maintained a federally-funded grant program since 1991 and has published more than 200 scientific articles in peer-reviewed journals.


Funding was supported by the NIH/NINDS grants R01 NS052470 and R01 NS039538 and NIH/NIMH grant R21 MH090494.

Conflict of interest statement There are no actual or potential conflicts of interest for the authors on this manuscript.


Abu-Amero, K.K., Al-Boudari, O.M., Mohamed, G.H., and Dzimiri, N. (2006). T null and M null genotypes of the glutathione S-transferase gene are risk factor for CAD independent of smoking. BMC. Med. Gen. 1, 38.10.1186/1471-2350-7-38Search in Google Scholar PubMed PubMed Central

Acosta-Cabronero, J., Williams, G.B., Pengas, G., and Nestor, P.J. (2010). Absolute diffusivities define the landscape of white matter degeneration in Alzheimer’s disease. Brain 133, 529–539.10.1093/brain/awp257Search in Google Scholar PubMed

Albers, D.S. and Beal, M.F. (2000). Mitochondrial dysfunction and oxidative stress in aging and neurodegenerative disease. Adv. Dement. Res. 59, 133–154.10.1007/978-3-7091-6781-6_16Search in Google Scholar PubMed

Allen, R.G. (1998). Oxidative stress and superoxide dismutase in development, aging and gene regulation. Age 21, 47–76.10.1007/s11357-998-0007-7Search in Google Scholar PubMed PubMed Central

Andersen, H.R., Nielsen, J.B., Nielsen, F., and Grandjean, P. (1997). Antioxidative enzyme activities in human erythrocytes. Clin. Chem. 43, 562–568.10.1093/clinchem/43.4.562Search in Google Scholar

Ansari, M.A. and Scheff, S.W. (2010). Oxidative stress in the progression of Alzheimer disease in the frontal cortex. J. Neuropathol. Exp. Neurol. 69, 155.10.1097/NEN.0b013e3181cb5af4Search in Google Scholar PubMed PubMed Central

Aoyama, K., Watabe, M., and Nakaki, T. (2008). Regulation of neuronal glutathione synthesis. J. Pharmacol. Sci. 108, 227–238.10.1254/jphs.08R01CRSearch in Google Scholar PubMed

Ardekani, S., Kumar, A., Bartzokis, G., and Sinha, U. (2007). Exploratory voxel-based analysis of diffusion indices and hemispheric asymmetry in normal aging. Magn. Reson. Imaging 25, 154–167.10.1016/j.mri.2006.09.045Search in Google Scholar PubMed

Armogida, M., Nisticò, R., and Mercuri, N.B. (2012). Therapeutic potential of targeting hydrogen peroxide metabolism in the treatment of brain ischaemia. Br. J. Pharmacol. 166, 1211–1224.10.1111/j.1476-5381.2012.01912.xSearch in Google Scholar PubMed PubMed Central

Artur, Y., Herbeth, B., Guémouri, L., Lecomte, E., Jeandel, C., and Siest, G. (1992). Age-related variations of enzymatic defenses against free radicals and peroxides. Free Radical Aging 62, 359–367.10.1007/978-3-0348-7460-1_36Search in Google Scholar PubMed

Assaf, Y. and Pasternak, O. (2008). Diffusion tensor imaging (DTI)-based white matter mapping in brain research: a review. J. Mol. Neurosci. 34, 51–61.10.1007/s12031-007-0029-0Search in Google Scholar

Auerbach, J.M. and Segal, M. (1997). Peroxide modulation of slow onset potentiation in rat hippocampus. J. Neurosci. 17, 8695–8701.10.1523/JNEUROSCI.17-22-08695.1997Search in Google Scholar

Babusikova, E., Evinova, A., Hatok, J., Dobrota, D., and Jurecekova, J. (2013a). Oxidative changes and possible effects of polymorphism of antioxidant enzymes in neurodegenerative disease. Medicine » Mental and Behavioural Disorders and Diseases of the Nervous System » “Neurodegenerative Diseases”, book Kishore, U., (ed). ISBN 978-953-51-1088-0, Published: May 15, 2013 under CC BY 3.0 license. DOI: 10.5772/54619.10.5772/54619Search in Google Scholar

Babusikova, E., Jesenak, M., Evinova, A., Banovcin, P., and Dobrota, D. (2013b). Frequency of polymorphism-262 C/T in catalase gene and oxidative damage in Slovak children with bronchial asthma. Arch. Bronconeumol. 49, 507–512.10.1016/j.arbr.2013.10.009Search in Google Scholar

Barnett, Y.A. and King, C.M. (1995). An investigation of antioxidant status, DNA repair capacity and mutation as a function of age in humans. Mutation Res./DNAging 338, 115–128.10.1016/0921-8734(95)00017-ZSearch in Google Scholar

Bartzokis, G. (2004). Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer’s disease. Neurobiol. Aging 25, 5–18.10.1016/j.neurobiolaging.2003.03.001Search in Google Scholar

Basser, P.J. and Pierpaoli, C. (2011). Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J. Magn. Reson. 213, 560–570.10.1016/j.jmr.2011.09.022Search in Google Scholar

Bennett, I.J. and Madden, D.J. (2013). Disconnected aging: cerebral white matter integrity and age-related differences in cognition. Neuroscience. doi: 10.1016/j.neuroscience.2013.11.026. [Epub ahead of print].10.1016/j.neuroscience.2013.11.026Search in Google Scholar

Bid, H.K., Konwar, R., Saxena, M., Chaudhari, P., Agrawal, C.G., and Banerjee, M. (2010). Association of glutathione S-transferase (GSTM1, T1 and P1) gene polymorphisms with type 2 diabetes mellitus in north Indian population. J. Postgrad. Med. 56, 176–81.10.4103/0022-3859.68633Search in Google Scholar

Borrás, C., Sastre, J., García-Sala, D., Lloret, A., Pallardó, F.V., and Viña, J. (2003). Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radical Biol. Aging 34, 546–552.10.1016/S0891-5849(02)01356-4Search in Google Scholar

Brigelius-Flohé, R. and Maiorino, M. (2013). Glutathione peroxidases. Biochim. Biophys. Acta 1830, 3289–3303.10.1016/j.bbagen.2012.11.020Search in Google Scholar PubMed

Brown, W.R. and Thore, C.R. (2011). Review: cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol. Appl. Neurobiol. 37, 56–74.10.1111/j.1365-2990.2010.01139.xSearch in Google Scholar PubMed PubMed Central

Burzynska, A.Z., Preuschhof, C., Bäckman, L., Nyberg, L., Li, S.C., Lindenberger, U., and Heekeren, H.R. (2010). Age-related differences in white matter microstructure: region-specific patterns of diffusivity. Neuroimage 3, 2104–2112.10.1016/j.neuroimage.2009.09.041Search in Google Scholar PubMed

Butterfield, D. A., Perluigi, M., & Sultana, R. (2006). Oxidative stress in Alzheimer’s disease brain: new insights from redox proteomics. European journal of pharmacology, 545, 39–50.10.1016/j.ejphar.2006.06.026Search in Google Scholar PubMed

Buxton, R.B. and Frank, L.R. (1997). A model for the coupling between cerebral blood flow and oxygen metabolism during neural stimulation. J. Cereb. Blood Flow Metab. 17, 64–72.10.1097/00004647-199701000-00009Search in Google Scholar PubMed

Caffarra, P., Vezzadini, G., Dieci, F., Zonato, F., and Venneri, A. (2004). Modified card sorting test: normative data. J. Clin. Exp. Neuropsychol. 26, 246–250.10.1076/jcen. in Google Scholar PubMed

Calabrese, V., Scapagnini, G., Ravagna, A., Colombrita, C., Spadaro, F., Butterfield, D.A., and Giuffrida Stella, A.M. (2004). Increased expression of heat shock proteins in rat brain during aging: relationship with mitochondrial function and glutathione redox state. Mech. Ageing Dev. 125, 325–335.10.1016/j.mad.2004.01.003Search in Google Scholar PubMed

Calingasan, N.Y. and Gibson, G.E. (2000). Vascular endothelium is a site of free radical production and inflammation in areas of neuronal loss in thiamine-deficient brain. Ann. N.Y. Acad. Sci. 903, 353–356.10.1111/j.1749-6632.2000.tb06386.xSearch in Google Scholar PubMed

Cannizzo, E.S., Clement, C.C., Sahu, R., Follo, C., and Santambrogio, L. (2011). Oxidative stress, inflammaging and immunosenescence. J. Proteom. 74, 2313–2323.10.1016/j.jprot.2011.06.005Search in Google Scholar PubMed

Capoluongo, E., Onder, G., Concolino, P., Russo, A., Santonocito, C., Bernabei, R., Zuppi, C., Ameglio, F., and Landi, F. (2009). GSTM1-null polymorphism as possible risk marker for hypertension: results from the aging and longevity study in the Sirente Geographic Area (ilSIRENTE study). Clin. Chim. Acta 399, 92–96.10.1016/j.cca.2008.09.017Search in Google Scholar PubMed

Carlsten, C., Sagoo, G.S., Frodsham, A.J., Burke, W., and Higgins, J.P.T. (2008). Glutathione S-transferase M1 (GSTM1) polymorphisms and lung cancer: a literature-based systematic HuGE review and meta-analysis. Am. J. Epidemiol. 167, 759–774.10.1093/aje/kwm383Search in Google Scholar

Chistiakov, D.A., Zotova, E.V., Savost’anov, K.V., Bursa, T.R., Galeev, I.V., Strokov, A., and Nosikov, V.V. (2006). The 262T→C promoter polymorphism of the catalase gene is associated with diabetic neuropathy in type 1 diabetic Russian patients. Diabetes Metab. 32, 63–68.10.1016/S1262-3636(07)70248-3Search in Google Scholar

Christiansen, L., Petersen, H.C., Bathum, L., Frederiksen, H., McGue, M., and Christensen, K. (2004). The catalase-262C/T promoter polymorphism and aging phenotypes. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 59, B886–B887.10.1093/gerona/59.9.B886Search in Google Scholar

Connor, J.R. and Menzies, S.L. (1996). Relationship of iron to oligondendrocytes and myelination. Glia 17, 83–93.10.1002/(SICI)1098-1136(199606)17:2<83::AID-GLIA1>3.0.CO;2-7Search in Google Scholar

Crack, P.J., Taylor, J.M., Flentjar, N.J., De Haan, J., Hertzog, P., Iannello, R.C., and Kola, I. (2001). Increased infarct size and exacerbated apoptosis in the glutathione peroxidase-1 (Gpx-1) knockout mouse brain in response to ischemia/reperfusion injury. J. Neurochem. 78, 1389–1399.10.1046/j.1471-4159.2001.00535.xSearch in Google Scholar

Crawford, A., Fassett, R.G., Geraghty, D.P., Kunde, D.A., Ball, M.J., Robertson, I.K., and Coombes, J.S. (2012). Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease. Gene 501, 89–103.10.1016/j.gene.2012.04.011Search in Google Scholar

Csiszar, A. and Ungvari, Z. (2010). Oxidative stress in vascular aging. In Studies on Cardiovascular Disorders. (Springer Science+Business Media, LLC: Humana Press). pp. 245–261. Print ISBN: 978-1-60761-599-6, Online ISBN: 978-1-60761-600-9. DOI: 10.1007/978-1-60761-600-9_13.10.1007/978-1-60761-600-9_13Search in Google Scholar

de Chaves, E.P. and Narayanaswami, V. (2008). Apolipoprotein E and cholesterol in aging and disease in the brain. Future Lipidol. 3, 505–530.10.2217/17460875.3.5.505Search in Google Scholar

D’esposito, M., Deouell, L.Y., and Gazzaley, A. (2003). Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging. Nat. Rev. Neurosci. 4 863–872.10.1038/nrn1246Search in Google Scholar

DeCarli, C., Fletcher, E., Ramey, V., Harvey, D., & Jagust, W. J. (2005). Anatomical mapping of white matter hyperintensities (wmh) exploring the relationships between periventricular WMH, deep WMH, and total WMH burden. Stroke, 36, 50–55.10.1161/01.STR.0000150668.58689.f2Search in Google Scholar

Dringen, R. (2000). Metabolism and functions of glutathione in brain. Prog. Neurobiol. 62, 649–671.10.1016/S0301-0082(99)00060-XSearch in Google Scholar

Dröge, W. (2005). Oxidative stress and ageing: is ageing a cysteine deficiency syndrome?. Philos. Trans. R. Soc. Lond. B Biol. Sci. 360, 2355–2372.10.1098/rstb.2005.1770Search in Google Scholar

Duffy, S.L., Lagopoulos, J., Hickie, I.B., Diamond, K., Graeber, M.B., Lewis, S.J., and Naismith, S.L. (2014). Glutathione relates to neuropsychological functioning in mild cognitive impairment. Alzheimers Dement. 10, 67–75.10.1016/j.jalz.2013.01.005Search in Google Scholar

Ebrahimi, A.P. (2009). Mechanical properties of normal and diseased cerebrovascular system. J. Vasc. Intervent. Dement. 2, 155.Search in Google Scholar

Farooqui, T. and Farooqui, A.A. (2009). Aging: an important factor for the pathogenesis of neurodegenerative diseases. Mech. Aging Dev. 130, 203–215.10.1016/j.mad.2008.11.006Search in Google Scholar

Fazekas, F., Chawluk, J. B., Alavi, A., Hurtig, H. I., & Zimmerman, R. A. (1987). MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. American Journal of Neuroradiology, 8, 421–426.Search in Google Scholar

Favreliere, S., Barrier, L., Durand, G., Chalon, S., and Tallineau, C. (1998). Chronic dietary n-3 polyunsaturated fatty acids deficiency affects the fatty acid composition of plasmenylethanolamine and phosphatidylethanolamine differently in rat frontal cortex, striatum, and cerebellum. Lipids 33, 401–407.10.1007/s11745-998-0221-ySearch in Google Scholar

Folstein, M.F., Folstein, S.E., and McHugh, P.R. (1975). “Mini-mental state” a practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12, 189–198.10.1016/0022-3956(75)90026-6Search in Google Scholar

Forsberg, L., Lyrenäs, L., Morgenstern, R., and de Faire, U. (2001). A common functional CT substitution polymorphism in the promoter region of the human catalase gene influences transcription factor binding, reporter gene transcription and is correlated to blood catalase levels. Free Radical Biol. Med. 30, 500–505.10.1016/S0891-5849(00)00487-1Search in Google Scholar

Foster, T.C. (2007). Calcium homeostasis and modulation of synaptic plasticity in the aged brain. Aging Cell. 6, 319–325.10.1111/j.1474-9726.2007.00283.xSearch in Google Scholar

Franco, A.A., Odom, R.S., and Rando, T.A. (1999). Regulation of antioxidant enzyme gene expression in response to oxidative stress and during differentiation of mouse skeletal muscle. Free Radical Biol. Med. 27, 1122–1132.10.1016/S0891-5849(99)00166-5Search in Google Scholar

Frazer, K.A., Murray, S.S., Schork, N.J., and Topol, E.J. (2009). Human genetic variation and its contribution to complex traits. Nat. Rev. Genet. 10, 241–251.10.1038/nrg2554Search in Google Scholar PubMed

Friedman, W.J. (2005). Interactions of interleukin-1 with neurotrophic factors in the central nervous system. Mol. Neurobiol. 32, 133–144.10.1385/MN:32:2:133Search in Google Scholar

Fujimura, M., Tominaga, T., and Chan, P.H. (2005). Neuroprotective effect of an antioxidant in ischemic brain injury. Neurocrit. Care 2, 59–66.10.1385/NCC:2:1:059Search in Google Scholar

Fukai, T., Folz, R.J., Landmesser, U., and Harrison, D.G. (2002). Extracellular superoxide dismutase and cardiovascular disease. Cardiovasc. Res. 55, 239–249.10.1016/S0008-6363(02)00328-0Search in Google Scholar

Fukui, K. and Urano, S. (2007). Neuronal damage, cognitive impairment and α-tocopherol. Oxon:The Encyclopedia of Vitamin E, CAB International, pp. 454–460.Search in Google Scholar

Ge, Y., Grossman, R.I., Babb, J.S., Rabin, M.L., Mannon, L.J., and Kolson, D.L. (2002). Age-related total gray matter and white matter changes in normal adult brain. Part I: volumetric MR imaging analysis. Am. J. Neuroradiol. 23, 1327–1333.Search in Google Scholar

Giorgio, A., Santelli, L., Tomassini, V., Bosnell, R., Smith, S., De Stefano, N., and Johansen-Berg, H. (2010). Age-related changes in grey and white matter structure throughout adulthood. Neuroimage 51, 943–951.10.1016/j.neuroimage.2010.03.004Search in Google Scholar

Girouard, H. and Iadecola, C. (2006). Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J. Appl. Physiol. 100, 328–335.10.1152/japplphysiol.00966.2005Search in Google Scholar

Glisky, E.L. (2007). Changes in Cognitive Function in Human Aging. In Brain aging: models, methods, and mechanisms, pp. 3–20. (Boca Raton, FL: CRC Press, Taylor & Francis Group).Search in Google Scholar

Gonzalez-Zulueta, M., Ensz, L.M., Mukhina, G., Lebovitz, R.M., Zwacka, R.M., Engelhardt, J.F., and Dawson, T.M. (1998). Manganese superoxide dismutase protects nNOS neurons from NMDA and nitric oxide-mediated neurotoxicity. J. Neurosci. 18, 2040–2055.10.1523/JNEUROSCI.18-06-02040.1998Search in Google Scholar

Grigsby, J., Kaye, K., and Robbins, L.J. (1995). Behavioral disturbance and impairment of executive functions among the elderly. Arch. Gerontol. Geriatr. 21, 167–177.10.1016/0167-4943(95)00636-YSearch in Google Scholar

Guemouri, L.Y.B.C.G.G., Artur, Y., Herbeth, B., Jeandel, C., Cuny, G., and Siest, G. (1991). Biological variability of superoxide dismutase, glutathione peroxidase, and catalase in blood. Clin. Chem. 37, 1932–1937.10.1093/clinchem/37.11.1932Search in Google Scholar

Hamanishi, T., Furuta, H., Kato, H., Doi, A., Tamai, M., Shimomura, H., Sakagashira, S., Nishi, M., Sasaki, H., Sanke, T., and Nanjo, K. (2004). Functional variants in the glutathione peroxidase-1 (GPx-1) gene are associated with increased intima-media thickness of carotid arteries and risk of macrovascular diseases in Japanese type 2 diabetic patients. Diabetes 53, 2455–2460.10.2337/diabetes.53.9.2455Search in Google Scholar

Harish, G., Venkateshappa, C., Mahadevan, A., Pruthi, N., Bharath, M.S., and Shankar, S.K. (2013). Mitochondrial function in human brains is affected by pre and post mortem factors. Neuropathol. Appl. Neurobiol. 39, 298–315.10.1111/j.1365-2990.2012.01285.xSearch in Google Scholar

Harris, S.E., Fox, H., Wright, A.F., Hayward, C., Starr, J.M., Whalley, L.J., and Deary, I.J. (2007). A genetic association analysis of cognitive ability and cognitive ageing using 325 markers for 109 genes associated with oxidative stress or cognition. BMC Genet. 8, 43.10.1186/1471-2156-8-43Search in Google Scholar

Harris, J.L., Yeh, H., Swerdlow, R.H., Choi, I., Lee, P., and Brooks, W.M. (2014). High-field proton magnetic resonance spectroscopy reveals metabolic effects of normal brain aging. Neurobiol. Aging 35, 1686.10.1016/j.neurobiolaging.2014.01.018Search in Google Scholar

Hayes, J.D. and Strange, R.C. (2000). Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 61, 154–166.10.1159/000028396Search in Google Scholar

Hayes, J.D., Flanagan, J.U., and Jowsey, I.R. (2005). Glutathione transferases. Ann. Rev. Pharmacol. Toxicol. 45, 51–88.10.1146/annurev.pharmtox.45.120403.095857Search in Google Scholar

Head, D., Buckner, R.L., Shimony, J.S., Williams, L.E., Akbudak, E., Conturo, T.E., McAvoy, M., Morris, J.C., and Snyder, A.Z. (2004). Differential vulnerability of anterior white matter in nondemented aging with minimal acceleration in dementia of the Alzheimer type: evidence from diffusion tensor imaging. Cereb. Cortex 14, 410–423.10.1093/cercor/bhh003Search in Google Scholar

Hensley, K., Robinson, K.A., Gabbita, S.P., Salsman, S., and Floyd, R.A. (2000). Reactive oxygen species, cell signaling, and cell injury. Free Radical Biol. Med. 28, 1456–1462.10.1016/S0891-5849(00)00252-5Search in Google Scholar

Hoehn, B., Yenari, M.A., Sapolsky, R.M., and Steinberg, G.K. (2003). Glutathione peroxidase overexpression inhibits cytochrome C release and proapoptotic mediators to protect neurons from experimental stroke. Stroke 34, 2489–2494.10.1161/01.STR.0000091268.25816.19Search in Google Scholar

Hollensworth, S. B., Shen, C. C., Sim, J. E., Spitz, D. R., Wilson, G. L., & LeDoux, S. P. (2000). Glial cell type-specific responses to menadione-induced oxidative stress. Free Radical Biology and Medicine, 28, 1161–1174.10.1016/S0891-5849(00)00214-8Search in Google Scholar

Holley, A.K., Dhar, S.K., and St Clair, D.K. (2010). Manganese superoxide dismutase versus p53: the mitochondrial center. Ann. N.Y. Acad. Sci. 1201, 72–78.10.1111/j.1749-6632.2010.05612.xSearch in Google Scholar PubMed

Holtzer, R., Burright, R.G., and Donovick, P.J. (2004). The sensitivity of dual-task performance to cognitive status in aging. J. Int. Neuropsychol. Soc. 10, 230–238.10.1017/S1355617704102099Search in Google Scholar PubMed

Jackman, K., & Iadecola, C. (2013). Neurovascular Regulation in the Ischemic Brain. Antioxidants & redox signaling.Search in Google Scholar

Jozefczak, M., Remans, T., Vangronsveld, J., and Cuypers, A. (2012). Glutathione is a key player in metal-induced oxidative stress defenses. Int. J. Mol. Sci. 13, 3145–3175.10.3390/ijms13033145Search in Google Scholar PubMed PubMed Central

Kachiwala, S.J., Harris, S.E., Wright, A.F., Hayward, C., Starr, J.M., Whalley, L.J., and Deary, I.J. (2005). Genetic influences on oxidative stress and their association with normal cognitive ageing. Neurosci. Lett. 386, 116–120.10.1016/j.neulet.2005.05.067Search in Google Scholar PubMed

Kannurpatti, S.S., Motes, M.A., Rypma, B., and Biswal, B.B. (2010). Neural and vascular variability and the fMRI-BOLD response in normal aging. Magnet. Reson. Imaging 28, 466–476.10.1016/j.mri.2009.12.007Search in Google Scholar PubMed PubMed Central

Kim, K.W., MacFall, J.R., and Payne, M.E. (2008). Classification of white matter lesions on magnetic resonance imaging in elderly persons. Biol. Psychiatry 64, 273–280.10.1016/j.biopsych.2008.03.024Search in Google Scholar PubMed PubMed Central

Kishida, K.T. and Klann, E. (2007). Sources and targets of reactive oxygen species in synaptic plasticity and memory. Antioxid. Redox Signal. 9, 233–244.10.1089/ars.2007.9.233Search in Google Scholar

Knapp, L.T. and Klann, E. (2002). Role of reactive oxygen species in hippocampal long-term potentiation: contributory or inhibitory? J. Neurosci. Res. 70, 1–7.10.1002/jnr.10371Search in Google Scholar PubMed

Kobayashi, N., DeLano, F.A., and Schmid-Schönbein, G.W. (2005). Oxidative stress promotes endothelial cell apoptosis and loss of microvessels in the spontaneously hypertensive rats. Artheroscler. Thromb. Vasc. Biol. 25, 2114–2121.10.1161/01.ATV.0000178993.13222.f2Search in Google Scholar PubMed

Kummer, U., Zobeley, J., Brasen, J.C., Fahmy, R., Kindzelskii, A.L., Petty, A.R., Clark, A. J., and Petty, H. R. (2007). Elevated glucose concentrations promote receptor-independent activation of adherent human neutrophils: an experimental and computational approach. Biophys. J. 92, 2597–2607.10.1529/biophysj.106.086769Search in Google Scholar PubMed PubMed Central

Kuzuya, M., Ando, F., Iguchi, A., and Shimokata, H. (2008). Glutathione peroxidase 1 Pro198Leu variant contributes to the metabolic syndrome in men in a large Japanese cohort. Am. J. Clin. Nutr. 87, 1939–1944.10.1093/ajcn/87.6.1939Search in Google Scholar PubMed

Ladiwala, U., Li, H., Antel, J.P., and Nalbantoglu, J. (1999). p53 Induction by tumor necrosis factor-α and involvement of p53 in cell death of human oligodendrocytes. J. Neurochem. 73, 605–611.10.1046/j.1471-4159.1999.0730605.xSearch in Google Scholar PubMed

Landeghem, G. F., Tabatabaie, P., Beckman, G., Beckman, L., & Andersen, P. M. (1999). Manganese‐containing superoxide dismutase signal sequence polymorphism associated with sporadic motor neuron disease. European Journal of Neurology, 6, 639–644.10.1046/j.1468-1331.1999.660639.xSearch in Google Scholar

Lakatta, E.G. (2002). Age-associated cardiovascular changes in health: impact on cardiovascular disease in older persons. Heart Fail. Rev. 7, 29–49.10.1023/A:1013797722156Search in Google Scholar

Lamar, M., Charlton, R.A., Ajilore, O., Zhang, A., Yang, S., Barrick, T.R., Rhodes, E., and Kumar, A. (2013). Prefrontal vulnerabilities and whole brain connectivity in aging and depression. Neuropsychologia 51, 1463–1470.10.1016/j.neuropsychologia.2013.05.004Search in Google Scholar

Landeghem, G.F., Tabatabaie, P., Beckman, G., Beckman, L., and Andersen, P.M. (1999). Manganese-containing superoxide dismutase signal sequence polymorphism associated with sporadic motor neuron disease. Eur. J. Neurol. 6, 639–644.10.1046/j.1468-1331.1999.660639.xSearch in Google Scholar

Laurent, S., Cockcroft, J., Van Bortel, L., Boutouyrie, P., Giannattasio, C., Hayoz, D., Pannier, B., Vlachopoulos, C., Wilkinson, I., Struijker-Boudier, H., et al. (2006). Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur. Heart J. 27, 2588–2605.10.1093/eurheartj/ehl254Search in Google Scholar

LeDoux, S. P., Druzhyna, N. M., Hollensworth, S. B., Harrison, J. F., & Wilson, G. L. (2007). Mitochondrial DNA repair: a critical player in the response of cells of the CNS to genotoxic insults. Neuroscience, 145, 1249–1259.10.1016/j.neuroscience.2006.10.002Search in Google Scholar

Lin, M.T. and Beal, M.F. (2006). Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443, 787–795.10.1038/nature05292Search in Google Scholar

Lindenberger, U. and von Oertzen, T. (2006). Variability in cognitive aging: from taxonomy to theory. Lifespan Cogn. Mech. Change 297–314. New York: Oxford University Press, Inc.Search in Google Scholar

Loguercio, C., Taranto, D., Vitale, L.M., Beneduce, F., and Del Vecchio Blanco, C. (1996). Effect of liver cirrhosis and age on the glutathione concentration in the plasma, erythrocytes, and gastric mucosa of man. Free Radical Biol. Med. 20, 483–488.10.1016/0891-5849(96)02057-6Search in Google Scholar

López-Armada, M.J., Riveiro-Naveira, R.R., Vaamonde-García, C., and Valcárcel-Ares, M.N. (2013). Mitochondrial dysfunction and the inflammatory response. Mitochondria 13, 106–118.10.1016/j.mito.2013.01.003Search in Google Scholar PubMed

Love, S. (1999). Oxidative stress in brain ischemia. Brain Pathol. 9, 119–131.10.1111/j.1750-3639.1999.tb00214.xSearch in Google Scholar

Lu, T., Pan, Y., Kao, S.Y., Li, C., Kohane, I., Chan, J., and Yankner, B.A. (2004). Gene regulation and DNA damage in the ageing human brain. Nature 429, 883–891.10.1038/nature02661Search in Google Scholar PubMed

Lubos, E., Loscalzo, J., and Handy, D.E. (2011). Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid. Redox. Signal. 15, 1957–1997.10.1089/ars.2010.3586Search in Google Scholar PubMed PubMed Central

Lynch, M.A. (1998). Analysis of the mechanisms underlying the age-related impairment in long-term potentiation in the rat. Rev. Neurosci. 9, 169–202.10.1515/REVNEURO.1998.9.3.169Search in Google Scholar PubMed

MacDonald, S.W., Nyberg, L., and Bäckman, L. (2006). Intra-individual variability in behavior: links to brain structure, neurotransmission and neuronal activity. Trends Neurosci. 29, 474–480.10.1016/j.tins.2006.06.011Search in Google Scholar PubMed

Madamanchi, N.R., Vendrov, A., and Runge, M.S. (2005). Oxidative stress and vascular disease. Artheroscler. Thromb. Vasc. Biol. 25, 29–38.10.1161/01.ATV.0000150649.39934.13Search in Google Scholar PubMed

Maillard, P., Crivello, F., Dufouil, C., Tzourio-Mazoyer, N., Tzourio, C., and Mazoyer, B. (2009). Longitudinal follow-up of individual white matter hyperintensities in a large cohort of elderly. Neuroradiology 51, 209–220.10.1007/s00234-008-0489-0Search in Google Scholar PubMed

Manfredi, S., Calvi, D., del Fiandra, M., Botto, N., Biagini, A., and Andreassi, M.G. (2009). Glutathione S-transferase T1-and M1-null genotypes and coronary artery disease risk in patients with type 2 diabetes mellitus. Cardiovasc. Pharmacogen. 10, 29–34.10.2217/14622416.10.1.29Search in Google Scholar PubMed

Mariani, E., Polidori, M.C., Cherubini, A., and Mecocci, P. (2005). Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview. J. Chromatogr. B 827, 65–75.10.1016/j.jchromb.2005.04.023Search in Google Scholar PubMed

Marner, L., Nyengaard, J.R., Tang, Y., and Pakkenberg, B. (2003). Marked loss of myelinated nerve fibers in the human brain with age. J. Comp. Neurol. 462, 144–152.10.1002/cne.10714Search in Google Scholar PubMed

Masella, R., Di Benedetto, R., Varì, R., Filesi, C., and Giovannini, C. (2005). Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes. J. Nutr. Biochem. 16, 577–586.10.1016/j.jnutbio.2005.05.013Search in Google Scholar PubMed

Mattson, M.P., Chan, S.L., and Duan, W. (2002). Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. Physiol. Rev. 82, 637–672.10.1152/physrev.00004.2002Search in Google Scholar

Mawhinney, L.J., de Rivero Vaccari, J.P., Dale, G.A., Keane, R.W., and Bramlett, H.M. (2011). Heightened inflammasome activation is linked to age-related cognitive impairment in Fischer 344 rats. BMC Neurosci. 12, 123.10.1186/1471-2202-12-123Search in Google Scholar

McTigue, D.M., and Tripathi, R.B. (2008). The life, death, and replacement of oligodendrocytes in the adult CNS. J. Neurochem. 107, 1–19.10.1111/j.1471-4159.2008.05570.xSearch in Google Scholar

Mecocci, P., MacGarvey, U., Kaufman, A.E., Koontz, D., Shoffner, J.M., Wallace, D.C., and Beal, M.F. (1993). Oxidative damage to mitochondrial DNA shows marked age dependent increases in human brain. Ann. Neurol. 34, 609–616.10.1002/ana.410340416Search in Google Scholar

Meister, A.M.E.A. and Anderson, M.E. (1983). Glutathione. Ann. Rev. Biochem. 52, 711–760.10.1146/ in Google Scholar

Miller, A.K.H., Alston, R.L., and Corsellis, J.A.N. (1980). Variation with age in the volumes of grey and white matter in the cerebral hemispheres of man: measurements with an image analyser. Neuropath. Appl. Neurobiol. 6, 119–132.10.1111/j.1365-2990.1980.tb00283.xSearch in Google Scholar

Mitrushina, M. and Satz, P. (1991). Changes in cognitive functioning associated with normal aging. Arch. Clin. Neurol. 6, 49–60.10.1093/arclin/6.1-2.49Search in Google Scholar

Mouzannar, R., Miric, S.J., Wiggins, R.C., and Konat, G.W. (2001). Hydrogen peroxide induces rapid digestion of oligodendrocyte chromatin into high molecular weight fragments. Neurochem. Int. 38, 9–15.10.1016/S0197-0186(00)00066-8Search in Google Scholar

Moy, G., Millet, P., Haller, S., Baudois, S., De Bilbao, F., Weber, K., Lövblad, K., Lazeyras, F., Giannakopoulos, P., and Delaloye, C. (2011). Magnetic resonance imaging determinants of intraindividual variability in the elderly: combined analysis of grey and white matter. Neuroscience 186, 88–93.10.1016/j.neuroscience.2011.04.028Search in Google Scholar PubMed

Muller, F.L., Lustgarten, M.S., Jang, Y., Richardson, A., and Van Remmen, H. (2007). Trends in oxidative aging theories. Free Radica Biol. Med. 43, 477–503.10.1016/j.freeradbiomed.2007.03.034Search in Google Scholar PubMed

Murray, A. D., Staff, R. T., Shenkin, S. D., Deary, I. J., Starr, J. M., & Whalley, L. J. (2005). Brain White Matter Hyperintensities: Relative Importance of Vascular Risk Factors in Nondemented Elderly People 1. Radiology, 237, 251–257.10.1148/radiol.2371041496Search in Google Scholar

Mythri, R.B., Venkateshappa, C., Harish, G., Mahadevan, A., Muthane, U.B., Yasha, T.C., Srinivas Bharath, M.M., and Shankar, S.K. (2011). Evaluation of markers of oxidative stress, antioxidant function and astrocytic proliferation in the striatum and frontal cortex of Parkinson’s disease brains. Neurochem. Res. 36, 1452–1463.10.1007/s11064-011-0471-9Search in Google Scholar

Mythri, R. B., Venkateshappa, C., Harish, G., Mahadevan, A., Muthane, U. B., Yasha, T. C., Bharath, M.M., and Shankar, S. K. (2011). Evaluation of markers of oxidative stress, antioxidant function and astrocytic proliferation in the striatum and frontal cortex of Parkinson’s disease brains. Neurochemical research, 36, 1452–1463.10.1007/s11064-011-0471-9Search in Google Scholar

Nicolle, M.M., Gonzalez, J., Sugaya, K., Baskerville, K.A., Bryan, D., Lund, K., Gallagher, M., and McKinney, M. (2001). Signatures of hippocampal oxidative stress in aged spatial learning-impaired rodents. Neurosci. 107, 415–431.10.1016/S0306-4522(01)00374-8Search in Google Scholar

Nilsson, P.M., Lurbe, E., and Laurent, S. (2008). The early life origins of vascular ageing and cardiovascular risk: the EVA syndrome. J. Hypertens. 26, 1049–1057.10.1097/HJH.0b013e3282f82c3eSearch in Google Scholar PubMed

Ogawa, S., Lee, T.M., Kay, A.R., and Tank, D.W. (1990). Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc. Natl. Acad. Sci. 87, 9868–9872.10.1073/pnas.87.24.9868Search in Google Scholar PubMed PubMed Central

Olmez, I. and Ozyurt, H. (2012). Reactive oxygen species and ischemic cerebrovascular disease. Neurochem. Int. 60, 208–212.10.1016/j.neuint.2011.11.009Search in Google Scholar PubMed

Paul, R.H., Haque, O., Gunstad, J., Tate, D.F., Grieve, S.M., Hoth, K., Brickman, A.M., Cohen, R., Lange, K., Jefferson, A.L., et al. (2005). Subcortical hyperintensities impact cognitive function among a select subset of healthy elderly. Arch. Clin. Neuropsychol. 20, 697–704.10.1016/j.acn.2005.02.004Search in Google Scholar PubMed PubMed Central

Paul, A., Belton, A., Nag, S., Martin, I., Grotewiel, M.S., and Duttaroy, A. (2007). Reduced mitochondrial SOD displays mortality characteristics reminiscent of natural aging. Mech. Aging Dev. 128, 706–716.10.1016/j.mad.2007.10.013Search in Google Scholar PubMed PubMed Central

Pera, J., Slowik, A., Dziedzic, T., Pulyk, R., Wloch, D., and Szczudlik, A. (2008). Glutathione peroxidase 1 C593T polymorphism is associated with lobar intracerebral hemorrhage. Cerebrovasc. Dis. 25, 445–449.10.1159/000126918Search in Google Scholar PubMed

Perrin, R., Briancon, S., Jeandel, C., Artur, Y., Minn, A., Penin, F., and Siest, G. (1990). Blood activity of Cu/Zn superoxide dismutase, glutathione peroxidase and catalase in Alzheimer’s disease: a case-control study. Gerontology 36, 306–313.10.1159/000213215Search in Google Scholar PubMed

Peters, A. (2002). The effects of normal aging on myelin and nerve fibers: a review. Journal of neurocytology, 31, 581–593.10.1023/A:1025731309829Search in Google Scholar

Peters, A., & Kemper, T. (2012). A review of the structural alterations in the cerebral hemispheres of the aging rhesus monkey. Neurobiology of aging, 33, 2357–2372.10.1016/j.neurobiolaging.2011.11.015Search in Google Scholar PubMed PubMed Central

Pfefferbaum, A., Mathalon, D.H., Sullivan, E.V., Rawles, J.M., Zipursky, R.B., and Lim, K.O. (1994). A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch. Neurol. 51, 874–887.10.1001/archneur.1994.00540210046012Search in Google Scholar PubMed

Piacentini, S., Polimanti, R., Squitti, R., Ventriglia, M., Cassetta, E., Vernieri, F., Rossini, P.M., Manfellotto, D., and Fuciarelli, M. (2012). GSTM1 null genotype as risk factor for late-onset Alzheimer’s disease in Italian patients. J. Neurol. Sci. 317, 137–140.10.1016/j.jns.2012.01.026Search in Google Scholar PubMed

Power, J.H. and Blumbergs, P.C. (2009). Cellular glutathione peroxidase in human brain: cellular distribution, and its potential role in the degradation of Lewy bodies in Parkinson’s disease and dementia with Lewy bodies. Acta Neuropath. 117, 63–73.10.1007/s00401-008-0438-3Search in Google Scholar PubMed

Rajaraman, P., Hutchinson, A., Rothman, N., Black, P.M., Fine, H.A., Loeffler, J.S., Selker, R.G., Shapiro, W.R., Linet, M.S., and Inskip, P.D. (2008). Oxidative response gene polymorphisms and risk of adult brain tumors. Neurooncology 10, 709–715.10.1215/15228517-2008-037Search in Google Scholar PubMed PubMed Central

Raven, J.C., Raven, J.C., and De Lemos, M.M. (1990). Standard Progressive Matrices (Oxford, United Kingdom: Oxford Psychologists Press).Search in Google Scholar

Reiter, R.J. (1995). Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J. 9, 526–533.10.1096/fasebj.9.7.7737461Search in Google Scholar

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). Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59–62.10.1038/362059a0Search in Google Scholar PubMed

Rodriguez-Rodriguez, R., & Simonsen, U. (2012). Measurement of nitric oxide and reactive oxygen species in the vascular wall. Current Analytical Chemistry, 8, 485–494.10.2174/157341112803216816Search in Google Scholar

Ross, B. and Bluml, S. (2001). Magnetic resonance spectroscopy of the human brain. Anat. Record. 265, 54–84.10.1002/ar.1058Search in Google Scholar

Rothwell, N.J. and Luheshi, G.N. (2000). Interleukin 1 in the brain: biology, pathology and therapeutic target. Trends Neurosci. 23, 618–625.10.1016/S0166-2236(00)01661-1Search in Google Scholar

Rouault, T.A. and Cooperman, S. (2006). Brain iron metabolism. Sem. Pediatr. Neurol. 13, 142–148.10.1016/j.spen.2006.08.002Search in Google Scholar PubMed

Rizvi, S. I., & Maurya, P. K. (2007). Markers of oxidative stress in erythrocytes during aging in humans. Annals of the New York Academy of Sciences, 1100, 373–382.10.1196/annals.1395.041Search in Google Scholar PubMed

Salat, D.H., Greve, D.N., Pacheco, J.L., Quinn, B.T., Helmer, K.G., Buckner, R.L., and Fischl, B. (2009). Regional white matter volume differences in nondemented aging and Alzheimer’s disease. Neuroimage 44, 1247–1258.10.1016/j.neuroimage.2008.10.030Search in Google Scholar PubMed PubMed Central

Salminen, A. and Kaarniranta, K. (2009). Regulation of the aging process by autophagy. Trends Mol. Med. 15, 217–224.10.1016/j.molmed.2009.03.004Search in Google Scholar PubMed

Sachdev, P., Chen, X., & Wen, W. (2008). White matter hyperintensities in mid-adult life. Current opinion in psychiatry, 21, 268–274.10.1097/YCO.0b013e3282f945d5Search in Google Scholar PubMed

Salminen, A., Kaarniranta, K., and Kauppinen, A. (2012). Inflammaging: disturbed interplay between autophagy and inflammasomes. Aging 4, 166.10.18632/aging.100444Search in Google Scholar PubMed PubMed Central

Salthouse, T.A. (2004). What and when of cognitive aging. Curr. Dir. Psychol. Sci. 13, 140–144.10.1111/j.0963-7214.2004.00293.xSearch in Google Scholar

Schriner, S.E., Linford, N.J., Martin, G.M., Treuting, P., Ogburn, C.E., Emond, M., Coskun, P.E., Ladiges, W., Wolf, N., Van Remmen, H., et al. (2005). Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308, 1909–1911.10.1126/science.1106653Search in Google Scholar PubMed

Serrano, F. and Klann, E. (2004). Reactive oxygen species and synaptic plasticity in the aging hippocampus. Ageing Res. Rev. 3, 431–443.10.1016/j.arr.2004.05.002Search in Google Scholar

Sharma, R., Yang, Y., Sharma, A., Awasthi, S., and Awasthi, Y.C. (2004). Antioxidant role of glutathione S transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis. Antioxid. Redox. Signal. 6, 289–300.10.1089/152308604322899350Search in Google Scholar

Shimoda-Matsubayashi, S., Matsumine, H., Kobayashi, T., Nakagawa-Hattori, Y., Shimizu, Y., and Mizuno, Y. (1996). Structural dimorphism in the mitochondrial targeting sequence in the human manganese superoxide dismutase gene: a predictive evidence for conformational change to influence mitochondrial transport and a study of allelic association in Parkinson’s disease. Biochem. Biophys. Res. Commun. 226, 561–565.10.1006/bbrc.1996.1394Search in Google Scholar

Sierra, C., Coca, A., and Schiffrin, E.L. (2011). Vascular mechanisms in the pathogenesis of stroke. Curr. Hypertens. Rep. 13, 200–207.10.1007/s11906-011-0195-xSearch in Google Scholar

Smith, K.J., Kapoor, R., and Felts, P.A. (1999). Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathol. 9, 69–92.10.1111/j.1750-3639.1999.tb00212.xSearch in Google Scholar

Soares, D.P. and Law, M. (2009). Magnetic resonance spectroscopy of the brain: review of metabolites and clinical applications. Clin. Radiol. 64, 12–21.10.1016/j.crad.2008.07.002Search in Google Scholar

Soerensen, M., Christensen, K., Stevnsner, T., and Christiansen, L. (2009). The Mn-superoxide dismutase single nucleotide polymorphism rs4880 and the glutathione peroxidase 1 single nucleotide polymorphism rs1050450 are associated with aging and longevity in the oldest old. Mech. Aging Dev. 130, 308–314.10.1016/j.mad.2009.01.005Search in Google Scholar

Söderlund, H., Nyberg, L., Adolfsson, R., Nilsson, L. G., & Launer, L. J. (2003). High prevalence of white matter hyperintensities in normal aging: relation to blood pressure and cognition. Cortex, 39, 1093–1105.10.1016/S0010-9452(08)70879-7Search in Google Scholar

Sowell, E.R., Peterson, B.S., Thompson, P.M., Welcome, S.E., Henkenius, A.L., and Toga, A.W. (2003). Mapping cortical change across the human life span. Nat. Neurosci. 6, 309–315.10.1038/nn1008Search in Google Scholar PubMed

Tang, N.P., Wang, L.S., Yang, L., Gu, H.J., Sun, Q.M., Cong, R.H., Zhou, B., Zhu, H.J., and Wang, B. (2008). Genetic variant in glutathione peroxidase 1 gene is associated with an increased risk of coronary artery disease in a Chinese population. Clin. Chim. Acta. 395, 89–93.10.1016/j.cca.2008.05.013Search in Google Scholar PubMed

Taufer, M., Peres, A., De Andrade, V.M., De Oliveira, G., Sá, G., do Canto, M.E.P., Dos Santos, A.R., Bauer, M.E., and da Cruz, I.B.M. (2005). Is the Val16Ala manganese superoxide dismutase polymorphism associated with the aging process? J. Gerontol. Ser. A Biol. Sci. Med. Sci. 60, 432–438.Search in Google Scholar

Thiels, E., Urban, N.N., Gonzalez-Burgos, G.R., Kanterewicz, B.I., Barrionuevo, G., Chu, C.T., Oury, T.D., and Klann, E. (2000). Impairment of long-term potentiation and associative memory in mice that overexpress extracellular superoxide dismutase. J. Neurosci. 20, 7631–7639.10.1523/JNEUROSCI.20-20-07631.2000Search in Google Scholar

Thomalla, G., Glauche, V., Koch, M.A., Beaulieu, C., Weiller, C., and Röther, J. (2004). Diffusion tensor imaging detects early Wallerian degeneration of the pyramidal tract after ischemic stroke. Neuroimage 22, 1767–1774.10.1016/j.neuroimage.2004.03.041Search in Google Scholar

Uberti, D., Yavin, E., Gil, S., Ayasola, K.R., Goldfinger, N., and Rotter, V. (1999). Hydrogen peroxide induces nuclear translocation of p53 and apoptosis in cells of oligodendroglia origin. Mol. Brain Res. 65, 167–175.10.1016/S0169-328X(98)00339-8Search in Google Scholar

Ulmann, L., Mimouni, V., Roux, S., Porsolt, R., and Poisson, J.P. (2001). Brain and hippocampus fatty acid composition in phospholipid classes of aged-relative cognitive deficit rats. Prostaglandins Leukot. Essent. Fatty Acids 64, 189–195.10.1054/plef.2001.0260Search in Google Scholar

Urano, S., Asai, Y., Makabe, S., Matsuo, M., Izumiyama, N., Ohtsubo, K., and Endo, T. (1997). Oxidative injury of synapse and alteration of antioxidative defense systems in rats, and its prevention by vitamin E. Eur. J. Biochem. 245, 64–70.10.1111/j.1432-1033.1997.00064.xSearch in Google Scholar

Urano, S., Sato, Y., Otonari, T., Makabe, S., Suzuki, S., Ogata, M., and Endo, T. (1998). Aging and oxidative stress in neurodegeneration. Biofactors 7, 103–112.10.1002/biof.5520070114Search in Google Scholar

Venkateshappa, C., Harish, G., Mahadevan, A., Bharath, M.S., and Shankar, S.K. (2012a). Elevated oxidative stress and decreased antioxidant function in the human hippocampus and frontal cortex with increasing age: implications for neurodegeneration in Alzheimer’s disease. Neurochem. Res. 37, 1601–1614.10.1007/s11064-012-0755-8Search in Google Scholar

Venkateshappa, C., Harish, G., Mythri, R.B., Mahadevan, A., Bharath, M.S., and Shankar, S.K. (2012b). Increased oxidative damage and decreased antioxidant function in aging human substantia nigra compared to striatum: implications for Parkinson’s disease. Neurochem. Res. 37, 358–369.10.1007/s11064-011-0619-7Search in Google Scholar

Wang, Y. and Walsh, S.W. (1996). Antioxidant activities and mRNA expression of superoxide dismutase, catalase, and glutathione peroxidase in normal and preeclamptic placentas. J. Soc. Gynecol. Investig. 3, 179–184.10.1016/1071-5576(96)00015-9Search in Google Scholar

Watson, J.B., Khorasani, H., Persson, A., Huang, K.P., Huang, F.L., and O’Dell, T.J. (2002). Age-related deficits in long-term potentiation are insensitive to hydrogen peroxide: coincidence with enhanced autophosphorylation of Ca2+/calmodulin-dependent protein kinase II. J. Neurosci. Res. 70, 298–308.10.1002/jnr.10427Search in Google Scholar PubMed

Watson, J.B., Arnold, M.M., Ho, Y.S., and O’Dell, T.J. (2006). Age-dependent modulation of hippocampal long-term potentiation by antioxidant enzymes. J. Neurosci. Res. 84, 1564–1574.10.1002/jnr.21040Search in Google Scholar

Wei, Y.H. and Lee, H.C. (2002). Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp. Biol. Med. 227, 671–682.10.1177/153537020222700901Search in Google Scholar

Wilson, J.X. (1997). Antioxidant defense of the brain: a role for astrocytes. Can. J. Physiol. Pharmacol. 75, 1149–1163.10.1139/y97-146Search in Google Scholar

Wiener, H. W., Perry, R. T., Chen, Z., Harrell, L. E., & Go, R. C. P. (2007). A polymorphism in SOD2 is associated with development of Alzheimer’s disease. Genes, Brain and Behavior, 6, 770–776.10.1111/j.1601-183X.2007.00308.xSearch in Google Scholar

Wosik, K., Antel, J., Kuhlmann, T., Brück, W., Massie, B., and Nalbantoglu, J. (2003). Oligodendrocyte injury in multiple sclerosis: a role for p53. J. Neurochem. 85, 635–644.10.1046/j.1471-4159.2003.01674.xSearch in Google Scholar

Yalin, S., Hatungil, R., Tamer, L., Ates, N.A., Dogruer, N., Yildirim, H., Karakas, S., and Atik, U. (2007). Glutathione S-transferase gene polymorphisms in Turkish patients with diabetes mellitus. Cell Biochem. Function. 25, 509–513.10.1002/cbf.1339Search in Google Scholar

Yehuda, S., Rabinovitz, S., Carasso, R.L., and Mostofsky, D.I. (2002). The role of polyunsaturated fatty acids in restoring the aging neuronal membrane. Neurobiol. Aging 23, 843–853.10.1016/S0197-4580(02)00074-XSearch in Google Scholar

Yoshita, M., Fletcher, E., Harvey, D., Ortega, M., Martinez, O., Mungas, D.M., Reed, B.R., and DeCarli, C.S. (2006). Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD. Neurology 67, 2192–2198.10.1212/01.wnl.0000249119.95747.1fSearch in Google Scholar PubMed PubMed Central

Zelinski, E.M. and Burnight, K.P. (1997). Sixteen-year longitudinal and time lag changes in memory and cognition in older adults. Psychol. Aging 12, 503.10.1037/0882-7974.12.3.503Search in Google Scholar

Zhu, X., Smith, M.A., Honda, K., Aliev, G., Moreira, P.I., Nunomura, A., Casadesus, G., Harris, P.L., Siedlak, S.L., and Perry, G. (2007). Vascular oxidative stress in Alzheimer disease. J. Neurol. Sci. 257, 240–246.10.1016/j.jns.2007.01.039Search in Google Scholar PubMed PubMed Central

Zotova, E.V., Savost’yanov, K.V., Chistyakov, D.A., Bursa, T.R., Galeev, I.V., Strokov, I.A., and Nosikov, V.V. (2004). Association of polymorphic markers of the antioxidant enzyme genes with diabetic polyneuropathy in type 1 diabetes mellitus. Mol. Biol. 38, 200–204.10.1023/B:MBIL.0000023735.60608.7aSearch in Google Scholar

Received: 2014-7-8
Accepted: 2014-7-17
Published Online: 2014-8-25
Published in Print: 2014-12-1

©2014 by De Gruyter

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