Accessible 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 and Robert H. Paul


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:


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.


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

©2014 by De Gruyter