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An Epigenetic Model for Susceptibility to Oxidative DNA Damage in the Aging Brain and Alzheimer’s Disease

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Aging and Age-Related Disorders

Abstract

Epigenetics and oxidative stress are two cellular mechanisms that appear to be independent from each other and associated with distinct cellular processes. Epigenetics is associated with developmental regulation of gene expression, mainly through the process of methylation of genetic promoter regions. On the other hand, oxidative stress is a cellular process of disruption in the homeostasis between cellular antioxidant systems and reactive oxygen and nitrogen species leading to cell malfunction or death. The oxidative stress process is linked to a myriad of diseases and is a consequence after toxicologic challenges. In this chapter, we summarize results from our laboratories that identify developmental stage and toxicologic challenges that result in a novel mechanism in which toxicologic exposure during development alters the normal pattern in markers of oxidative stress and epigenetic regulation. The concordance of these two alterations results in pathologic changes similar to those seen in Alzheimer’s disease. Thus, we postulate a novel mechanism in which epigenetics and oxidative stress are at play in disease, and the occurrence of one of these processes will alter the occurrence of the other.

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Acknowledgments

We wish to express our sincere gratitude to the thoughtful comments and suggestions by Professor D. Lahiri in the development of this model. We also would like to thank Dr. Jinfang Wu and Hassan Siddiqi in performing some of the modeling experiments and Remi Dosunmu for editing the manuscript. This research was supported by the National Institute of Environmental Health Sciences (NIEHS) and the National Institute of Aging through grants (ES013022 and AG027246) awarded to N.H.Z.. The research core facility at URI was funded (P20RR016457) by the National Center for Research Resources (NCRR), a component of NIH. This work was also supported by a grant from the National Institute of Aging (AG031184) awarded to F.C. and by support he has received from NCRR (P20 RR015583 and P20RRP20RR017670).

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Authors and Affiliations

  1. Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, 02881, USA

    Nasser H. Zawia

  2. Department of Biomedical and Pharmaceutical Sciences, Center for Environmental Health Sciences, University of Montana, Missoula, MT, 59812, USA

    Fernando Cardozo-Pelaez

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  1. Nasser H. Zawia
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  2. Fernando Cardozo-Pelaez
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Correspondence to Nasser H. Zawia .

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Editors and Affiliations

  1. Center for Occupational & Environmental, Department of Medicine, University of California, Irvine, Room 320, Med Surge II, Irvine, 92697, California, USA

    Stephen Bondy

  2. New Jersey Medical School, Department of Neurology and Neuroscience, University of Medicine & Dentistry of Ne, South Orange Avenue 185, Newark, 07101, New Jersey, USA

    Kenneth Maiese

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Zawia, N.H., Cardozo-Pelaez, F. (2010). An Epigenetic Model for Susceptibility to Oxidative DNA Damage in the Aging Brain and Alzheimer’s Disease. In: Bondy, S., Maiese, K. (eds) Aging and Age-Related Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-602-3_22

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