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Science Forum Index » Life Extension Forum » Advanced glycation end product homeostasis: exogenous...
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| Olafur Pall Olafsson... |
 Posted: Sun May 04, 2008 5:43 pm |
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The full text is a good reading for those with access to it. Below I
post a few quotes from it.
Ann N Y Acad Sci. 2008 Apr;1126:46-52.
Related Articles, Links
Click here to read
Advanced glycation end product homeostasis: exogenous oxidants and
innate defenses.
Vlassara H, Uribarri J, Cai W, Striker G.
Mount Sinai School of Medicine, Box 1640, One Gustave Levy Place,
New York, NY 10029. helen.vlassara at (no spam) mssm.edu.
Increased oxidative stress (OS) underlies many chronic diseases
prevalent in aging. Data in humans confirm the hypothesis that
advanced glycation end products (AGEs) and other oxidants derived from
the diet may be major contributors to increased OS in normal adults as
well as those with diabetes mellitus or kidney failure. Mice fed a
diet with a lowered (approximately 50%) content of AGEs or a typical
calorie-restricted (CR) diet, accumulated a smaller amount of AGEs,
maintained normal levels of AGE receptor-1 (AGER1), and did not have
increased oxidant stress or cardiac or kidney fibrosis with aging.
However, the findings in mice fed a CR diet with an increased content
of AGEs resembled those in mice fed a nonrestricted diet that had the
usual higher content of AGEs. Thus, there was an inverse correlation
between the dietary AGE content, the AGER1 to receptor for AGE (RAGE)
ratio, OS, organ damage, and life span. In both humans and mice, there
was an inverse correlation between the AGER1 to RAGE ratio and the
levels of OS.
PMID: 18448795 [PubMed - in process]
Related Articles
* Reduced oxidant stress and extended lifespan in mice exposed
to a low glycotoxin diet: association with increased AGER1 expression.
[Am J Pathol. 2007]
* AGE-receptor-1 counteracts cellular oxidant stress induced
by AGEs via negative regulation of p66shc-dependent FKHRL1
phosphorylation. [Am J Physiol Cell Physiol. 2008]
* Advanced glycation end product (AGE) receptor 1 suppresses
cell oxidant stress and activation signaling via EGF receptor. [Proc
Natl Acad Sci U S A. 2006]
* Circulating glycotoxins and dietary advanced glycation
endproducts: two links to inflammatory response, oxidative stress, and
aging. [J Gerontol A Biol Sci Med Sci. 2007]
* Advanced glycation end product ligands for the receptor for
advanced glycation end products: biochemical characterization and
formation kinetics. [Anal Biochem. 2004]
* » See all Related Articles...
Here are a few quotes from the full text:
"AGEs are modified in the body by enzymatic degradation, innate
defenses, and receptor-dependent uptake and degradation. The major
degradative enzymes involved are the glyoxalase I and II system. For
example, highly reactive AGE precursor molecules, such as
methylglyoxal (MG), are detoxified by glyoxalase I and II at a rate
proportional to the cytosolic levels of glutathione.4 Another route of
detoxification is through their reduction by aldose reductase and
carbonyl reductase, which is catalyzed by aldehyde reductase.5 There
is also a group of circulating proteins that bind AGEs keeping them
from causing cellular toxicity or binding to other molecules.6 These
proteins are part of the innate defense system and include lysozyme,
defensins, and lactoferrin.6,7"
"There are two types of cell surface AGE receptors and molecules,
those which bind AGEs and initiate cell activation8 and those that
bind, internalize, and degrade AGEs (7). The best-studied receptor
that binds and initiates OS is the receptor for AGE (RAGE).8 It
recognizes AGEs as one of many ligands, is not endocytic, and is
upregulated by OS. The second group of AGE receptors binds AGEs and
mediates endocytosis and degradation of AGEs. This group includes the
AGE receptor-1 (AGER1), AGER3, and CD36.1,7,9 These systems help
maintain normal AGE homeostasis throughout life under normal
conditions, but not under conditions of chronically elevated AGEs and
OS, such as in diabetes mellitus and aging.3,10 The most extensively
evaluated of the endocytic AGE receptors is AGER1, which has marked
antioxidant properties modulating AGE responses via RAGE and nuclear
factor kappa-B7,9 but also via the epidermal growth factor receptor,
extracellular receptor kinase, and p66shc.9 As a consequence, the
AGER1 to RAGE ratio is an important element of the defense against
excess OS. The importance of this ratio is emphasized by the
observation that when AGER1 levels are suppressed, the levels of OS
are elevated (Figs. 1 and 2). Examples of these events include
diabetes mellitus and late aging.3,10 Thus, we hypothesize that a
decrease in the level or function of AGER1 is one reason for the
increased OS found in diabetes and late aging."
"Because AGEs have been shown to upregulate cellular AGE uptake,
partly through an AGER1-mediated mechanism, the increased expression
of AGER1 in mice fed diets with a low content of AGEs suggests that
AGER1 can respond to, and effectively handle, fluctuations in AGE load
in vivo, if this load does not exceed a certain threshold. However,
under conditions of chronically elevated exogenous AGEs, AGER1 levels
are suppressed. As a result of decreased AGER1 levels, the capacity of
the body to handle oxidants is reduced."
"The increased levels of AGEs and related inflammatory changes in both
mice and humans appear to be partly a result of decreased levels of
AGER1. The resultant changed AGER1 to RAGE ratio is associated with
increased OS. These findings are pertinent to the normal population
where consumption of large amounts of AGEs and related oxidants
represents an independent factor for increased OS and inflammation.
These factors can be modulated acutely, but if they remain chronically
elevated, they may be associated with the development of several
chronic diseases related to aging. These findings highlight the
importance of consuming diets with a low-AGE content." |
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| Posted: Fri May 09, 2008 1:40 pm |
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Guest
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Excellent post Olafur. I suspect AGER1 is incapacitated by oxidative
stress.(H2O2)......If so maintaining high levels of glutathione via
NAC and lipoic acid should be an effective means of maintaining its
activity. I haven't seen the structure of the enzyme. If you come
across it should of course have cysteine or methionine residues near
or at its active site.
Tim |
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