PMID- 23336521
OWN - NLM
STAT- MEDLINE
DCOM- 20130513
LR  - 20231003
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 125
IP  - 1
DP  - 2013 Apr
TI  - Aging is associated with altered inflammatory, arachidonic acid cascade, and 
      synaptic markers, influenced by epigenetic modifications, in the human frontal 
      cortex.
PG  - 63-73
LID - 10.1111/jnc.12153 [doi]
AB  - 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.
CI  - Published 2013. This article is a U.S. Government work and is in the public 
      domain in the USA.
FAU - Keleshian, Vasken L
AU  - Keleshian VL
AD  - Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National 
      Institute on Aging, National Institutes of Health, Bethesda, MD 20892-0947, USA.
FAU - Modi, Hiren R
AU  - Modi HR
FAU - Rapoport, Stanley I
AU  - Rapoport SI
FAU - Rao, Jagadeesh S
AU  - Rao JS
LA  - eng
GR  - R24 MH068855/MH/NIMH NIH HHS/United States
GR  - R99 AG999999/AG/NIA NIH HHS/United States
GR  - Z99 AG999999/ImNIH/Intramural NIH HHS/United States
GR  - R24MH068855/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Retracted Publication
DEP - 20130217
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Biomarkers)
RN  - 27YG812J1I (Arachidonic Acid)
SB  - IM
RIN - J Neurochem. 2017 Mar;140(6):980. PMID: 28261875
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aging/immunology/*metabolism
MH  - Apoptosis
MH  - Arachidonic Acid/*metabolism
MH  - Biomarkers/metabolism
MH  - DNA Methylation
MH  - *Epigenesis, Genetic
MH  - Frontal Lobe/*metabolism
MH  - Humans
MH  - Inflammation/metabolism
MH  - Middle Aged
MH  - Synapses/*metabolism
PMC - PMC3606672
MID - NIHMS437525
COIS- Conflicts of interests: None
EDAT- 2013/01/23 06:00
MHDA- 2013/05/15 06:00
PMCR- 2014/04/01
CRDT- 2013/01/23 06:00
PHST- 2012/10/01 00:00 [received]
PHST- 2012/12/17 00:00 [revised]
PHST- 2012/12/18 00:00 [accepted]
PHST- 2013/01/23 06:00 [entrez]
PHST- 2013/01/23 06:00 [pubmed]
PHST- 2013/05/15 06:00 [medline]
PHST- 2014/04/01 00:00 [pmc-release]
AID - 10.1111/jnc.12153 [doi]
PST - ppublish
SO  - J Neurochem. 2013 Apr;125(1):63-73. doi: 10.1111/jnc.12153. Epub 2013 Feb 17.