Document Detail


Aging is associated with altered inflammatory, arachidonic acid cascade, and synaptic markers, influenced by epigenetic modifications, in the human frontal cortex.
MedLine Citation:
PMID:  23336521     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Vasken L Keleshian; Hiren R Modi; Stanley I Rapoport; Jagadeesh S Rao
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-02-17
Journal Detail:
Title:  Journal of neurochemistry     Volume:  125     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-22     Completed Date:  2013-05-13     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  63-73     Citation Subset:  IM    
Copyright Information:
Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Aging / immunology,  metabolism*
Apoptosis
Arachidonic Acid / metabolism*
Biological Markers / metabolism
DNA Methylation
Epigenesis, Genetic*
Frontal Lobe / metabolism*
Humans
Inflammation / metabolism
Middle Aged
Synapses / metabolism*
Grant Support
ID/Acronym/Agency:
R24MH068855/MH/NIMH NIH HHS; Z99 AG999999/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 27YG812J1I/Arachidonic Acid
Comments/Corrections

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