Aging is associated with altered inflammatory, arachidonic acid cascade, and synaptic markers, influenced by epigenetic modifications, in the human frontal cortex
Article first published online: 17 FEB 2013
Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
Journal of Neurochemistry
Volume 125, Issue 1, pages 63–73, April 2013
How to Cite
J. Neurochem.(2013) 125, 63–73.
- Issue published online: 21 MAR 2013
- Article first published online: 17 FEB 2013
- Accepted manuscript online: 22 JAN 2013 04:46AM EST
- Manuscript Accepted: 18 DEC 2012
- Manuscript Revised: 17 DEC 2012
- Manuscript Received: 1 OCT 2012
- Intramural Research Program of the National Institute on Aging, National Institutes of Health, Bethesda, MD USA
- arachidonic acid;
- BDNF ;
- CREB ;
- DNA methylation;
Aging is a risk factor for Alzheimer's disease (AD) and is associated with cognitive decline. However, underlying molecular mechanisms of brain aging are not clear. Recent studies suggest epigenetic influences on gene expression in AD, as DNA methylation levels influence protein and mRNA expression in postmortem AD brain. We hypothesized that some of these changes occur with normal aging. To test this hypothesis, we measured markers of the arachidonic acid (AA) cascade, neuroinflammation, pro- and anti-apoptosis factors, and gene specific epigenetic modifications in postmortem frontal cortex from nine middle-aged [41 ± 1 (SEM) years] and 10 aged subjects (70 ± 3 years). The aged compared with middle-aged brain showed elevated levels of neuroinflammatory and AA cascade markers, altered pro and anti-apoptosis factors and loss of synaptophysin. Some of these changes correlated with promoter hypermethylation of brain derived neurotrophic factor (BDNF), cyclic AMP responsive element binding protein (CREB), and synaptophysin and hypomethylation of BCL-2 associated X protein (BAX). These molecular alterations in aging are different from or more subtle than changes associated with AD pathology. The degree to which they are related to changes in cognition or behavior during normal aging remains to be evaluated.