I was thinking the other night as I was gleefully browning some chicken before making a beautiful white wine/mushroom/shallot/cream sauce: "here I am taking all of these supplements to extend life, some of which are designed to inhibit the formation of AGEs, and I am ingesting AGEs deliberately"
I decided that too live forever on porridge and sprouts is worse than dying young and having lived. Now, Thomas Carter at sci.life-extension has given me hope by posting these abstracts.
These three show potential benefits of dietary AGE's.
17: FASEB J. 2004 Dec;18(15):1812-7. Related Articles, Links
Antagonism of RAGE suppresses peripheral nerve regeneration.
Rong LL, Trojaborg W, Qu W, Kostov K, Yan SD, Gooch C, Szabolcs M, Hays
AP, Schmidt AM.
Department of Surgery, Columbia University Medical Center, New York,
New York 10032, USA.
Axotomy of peripheral nerve triggers events that
coordinate a limited inflammatory response to axonal degeneration and
initiation of neurite outgrowth. Inflammatory and neurite
outgrowth-promoting roles for the receptor for advanced glycation end
products (RAGE) have been suggested, so we tested its role in
peripheral nerve regeneration. Analysis of immunohistochemical
localization of RAGE by confocal microscopy revealed that RAGE was
expressed in axons and infiltrating mononuclear phagocytes upon
unilateral sciatic nerve crush in mice. Administration of soluble RAGE,
the extracellular ligand binding domain of RAGE, or blocking F(ab')2
fragments of antibodies raised to either RAGE or its ligands,
S100/calgranulins or amphoterin, reduced functional recovery as
assessed by motor and sensory nerve conduction velocities and sciatic
functional index and reduced regeneration, as assessed by myelinated
fiber density after acute crush of the sciatic nerve. In parallel, in
mice subjected to RAGE blockade, decreased numbers of mononuclear
phagocytes infiltrated the distal nerve segments after crush. These
findings provide the first evidence of an innate function of the
ligand/RAGE axis and suggest that RAGE plays an important role in
regeneration of the peripheral nervous system.
PMID: 15576484
18: Carcinogenesis. 2004 Nov 11; [Epub ahead of print] Related
Articles, Links
Down-regulation of the receptor for advanced glycation end-products
(RAGE) supports non-small cell lung carcinoma.
Bartling B, Hofmann HS, Weigle B, Silber RE, Simm A.
Clinic of Cardio-thoracic Surgery, Martin Luther University
Halle-Wittenberg, Halle/Saale, Germany.
The receptor for advanced glycation end-products (RAGE) is
a transmembrane receptor of the immunoglobulin superfamily. Several
ligands binding to RAGE have been identified, including amphoterin.
Experimental studies have given rise to the discussion that RAGE and
its interaction with amphoterin contribute to tumour growth and
metastasis. However, none of the studies consider a differential
transcription profile in cancer that might change the interpretation of
the study results when comparing RAGE in tumours with histologically
normal tissues. Here we show that RAGE is strongly reduced on mRNA and
even more so on a protein level in non-small cell lung carcinomas
compared with normal lung tissues. Down-regulation of RAGE correlates
with higher tumour (TNM) stages but does not depend on the histological
subtypes, squamous cell lung carcinoma and adenocarcinoma. Subsequent
over-expression of full-length human RAGE in lung cancer cells
(NCI-H358) showed a diminished tumour growth in some conditions. While
the proliferation of RAGE-expressing cells was less than that of cells
expressing the cytoplasmic domain deletion mutant DeltacytoRAGE or
mock-transfected NCI-H358 in monolayer cultures, RAGE cells also formed
smaller tumours in spheroid cultures and in vivo in athymic mice
compared with DeltacytoRAGE cells. Moreover, we observed a more
epithelial growth of RAGE- but also of DeltacytoRAGE-expressing cells
on collagen layers, whereas mock NCI-H358 cells kept their tumour
morphology. This observation was supported by immunofluorescence
analyses demonstrating that RAGE preferentially localizes at the
intercellular contact sites independent of the expression of the
cytoplasmic domain. Thus, down-regulation of RAGE may be considered as
a critical step in tissue reorganization and the formation of lung
tumours.
PMID: 15539404
19: J Nutr Biochem. 1999 Jun;10(6):372-6. Related Articles, Links
Antioxidant effects of fructosyl arginine, a Maillard reaction product
in aged garlic extract.
Ide N, Lau BH, Ryu K, Matsuura H, Itakura Y.
Department of Microbiology and Molecular Genetics, School of Medicine,
Loma Linda University, Loma Linda, CA USA.
The amino-carbonyl (Maillard) reaction of amino acids
with sugars is a nonenzymatic browning reaction that takes place during
the processing, cooking, and storage of foods. Maillard reaction
products (MRPs) have been shown to possess interesting chemical and
biological properties including antimutagenic and antioxidant activity.
In this study, we determined the antioxidant effects of fructosyl
arginine (Fru-Arg), a MRP in aged garlic extract. Low density
lipoprotein (LDL) was incubated with Cu(2+) at 37 degrees C and 5%
CO(2) for 24 hours, which resulted in an increase of thiobarbituric
acid reactive substances (TBARS) indicating lipid peroxidation.
Coincubation of Cu(2+) with Fru-Arg and LDL resulted in a significant
inhibition of TBARS formation. Pulmonary artery endothelial cells
(PAEC) were exposed to 0.1 mg/mL oxidized LDL (Ox-LDL) at 37 degrees C
and 5% CO(2) for 24 hours. Lactate dehydrogenase (LDH) release, as an
index of cell membrane damage, and TBARS were measured. Ox-LDL caused
an increase of LDH release and TBARS formation. Pretreatment of PAEC
with Fru-Arg inhibited these changes. Murine macrophages were incubated
with Ox-LDL, and the release of peroxides was measured using a
fluorometric assay. Ox-LDL caused an increased release of peroxides.
Coincubation of macrophages with Fru-Arg and Ox-LDL inhibited the
release of peroxides dose-dependently. In a cell free system, Fru-Arg
was shown to scavenge hydrogen peroxide. These data suggest that
Fru-Arg is a potent antioxidant, and thus may be useful for the
prevention of atherosclerosis and other disorders associated with
oxidative stress.
PMID: 15539313
