Everyone,
I looked up both lipofucin and advanced glycation end-products on
medline and found the following few abstracts linking the two
substances together. It seems to me, after reading these abstracts,
that in reality lipofucin might really be just a mixture of AGEs and
other similar crosslinked substances.
If this turns out to be true, it seems like ALT-711 should have at
least "some" effect on lipofucin and could possibly even help
eliminate it from human cells.
Just recently, the phase one trials of ALT-711 were completed. If the
results of the trials show that it is non-toxic and safe, then we
might have a drug that could potentially eliminate at least two of the
aspects of the aging process....
Maybe two down... So many more to go....
Anyway, here are the abstracts.
Best Regards,
William
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Biochemical basis of lipofuscin, ceroid, and age pigment-like
fluorophores.
Yin D
Free Radic Biol Med 1996 21:6 871-88
Abstract
Serious studies of the formation mechanisms of age-related pigments
and their possible cellular influence have been hampered for a long
time by discrepancies and controversies over the definition,
fluorescence emission, origin, and composition of these pigments. This
review discusses several critical controversies in this field and lay
special emphasis on the cellular and biochemical reactions related to
the formation mechanisms of lipofuscin, ceroid, advanced glycation
end-products (AGEs), and age pigment like fluorophores (APFs). Various
amino compounds and their reaction with secondary aldehydic products
of oxygen free radical-induced oxidation, particularly lipid
peroxidation, are important sources of the fluorophores of
ceroid/lipofuscin, which progressively accumulate as a result of
phagocytosis and autophagocytosis of modified biomaterials within
secondary lysosomes of postmitotic and other cells. Lipofuscin is the
classical age pigment of postmitotic cells, while ceroid accumulates
due to pathologic and experimental processes. There are good reasons
to consider both ceroid and lipofuscin as materials of the same
principal origin. The age-related intracellular fluorophores of
retinal pigment epithelium (RPE) seems to represent a special class of
lipofuscin, which partly contains derivatives of retinoids and
carotenoids. Saccharide-originated fluorophores, principally AGEs
formed during glycation/Maillard reactions, may be mainly responsible
for the extracellular fluorescence of long-lived proteins, such as
collagen, elastin, and lens crystalline. Although lipofuscin, ceroid,
AGEs, and APFs can be produced from different types of biological
materials due to different side reactions of essential biology, the
crosslinking of carbonyl-amino compounds is recognized as a common
process during their formation.
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Immunohistochemical localization of advanced glycation end products,
pentosidine, and carboxymethyllysine in lipofuscin pigments of
Alzheimer's disease and aged neurons.
Horie K, Miyata T, Yasuda T, Takeda A, Yasuda Y, Maeda K, Sobue G,
Kurokawa K
Biochem Biophys Res Commun 1997 Jul 18 236:2 327-32
Abstract
Lipofuscins are intracellular fluorescent pigments accumulating in the
central nervous system (CNS) with aging and degenerative processes
such as Alzheimer's disease (AD). Although they are thought to be
lipid peroxidation products derived from malondialdehyde, their
biogenesis remains controversial. We further characterize the chemical
nature of lipofuscins in brain tissues from AD patients and normal
aged subjects. Advanced glycation end products (AGEs), pentosidine and
carboxymethyllysine (CML), were identified by appropriate specific
antibodies. They have physicochemical properties similar to those of
lipofuscin and also increase with aging. Pentosidine and CML were
identified in the neuronal perikarya and the extraneuroperikaryal
deposits of both the AD and aged brain. Pentosidine, but not CML, was
present in the fiber-like structure within the neuropil and the core
of classical senile plaque. In the brain of young subjects without CNS
disease, pentosidine and CML staining was faint. Pentosidine and CML
co-localized with lipofuscin pigments in the neuronal perikarya of
both the AD and aged brain. We demonstrate for the first time that
lipofuscin is constituted not only of lipid peroxidation products but
also from glycation products which may be the origin of fluorescent
pigments. Lipofuscins should thus be considered as fluorescent
pigments generated by lipid- and sugar-derived Schiff base-protein
polymers.
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The liver cell histones of diabetic patients contain glycation
endproducts (AGEs) which may be lipofuscin components [letter]
Jobst K, Lakatos A
Clin Chim Acta 1996 Dec 30 256:2 203-4
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Studies on age pigments evolving into a new theory of biological
aging.
Yin D
Gerontology 1995 41 Suppl 2: 159-72
Abstract
A variety of age pigment-like fluorophores have been recognized,
identified and investigated during the past three decades. They are
mainly the end-products of various side-reactions of essential
biological processes. Among these, the lipid peroxidation-related
fluorophores formed via aldehyde-protein crosslinking are of general
importance. Fluorescent advanced glycation end-products formed during
glycation/Maillard reactions, are oxygen independent,
carbohydrate-associated age pigment-like substances. Age pigments,
particularly those identified in retinal pigment epithelium, represent
another type of age pigment that originates from polyenic
biomolecules, including retinoids and carotenoids. Various alpha
beta-unsaturated aldehydes can also react with the amino groups of
nucleotides to induce biological alteration. Although age pigments can
be produced from different types of biological materials, the
crosslinking of carbonyl and amino compounds is a common toxiferous
process during biological life. In the context of various aging
phenomena and degenerative diseases, this process may constitute an
essential mechanism of aging--the carbonyl toxification process of
biological aging.