The amino acid carnosine is a natural AGE inhibitor found in high
concentrations in the brain, muscle tissue and the lens of the human eye. It
is also known to be an antioxidant capable of protecting cell membranes and
other cell structures. In vitro studies demonstrated that carnosine inhibits
glycosylation and crosslinking of proteins induced by reactive aldehydes,
and that it is effective in reducing AGE formation by competing with
proteins for binding with the sugars. The authors suggest that this nontoxic
compound should be explored in the treatment of such conditions as diabetic
complications, inflammatory disorders, alcoholic liver disease and possibly
Alzheimer's disease (Hipkiss AR et al., 1998).
Many additional functions for carnosine have been suggested, such as
immunomodulator, neurotransmitter, metal ion chelator and wound healing
agent. In a series of animal studies it was demonstrated that carnosine was
effective in overcoming muscle fatigue, lowering blood pressure, reducing
stress and hyperactivity and inducing sleep (Quinn PR et al., 1992). More
recently carnosine was shown to delay senescence in cultured human
fibroblasts (McFarland GA et al., 1994).
In an animal study on the effect of carnosine in the ischemic brain,
carnosine had a protective effect, preserving nerve cells from damage and
death, suggesting that this amino acid might be a promising treatment for
patients with stroke (Stvolinsky, SL et al., 1998). In other studies
carnosine was shown to be effective in the treatment of senile cataracts in
dogs, suggesting the possible use of carnosine in the prevention and
treatment of cataracts in humans (Halliwell B et al., 1985).
Along with carnosine, lipoic acid has been shown to control the formation of
AGE and reduce protein damage from glycation in both humans and animals.
This has proven to be of special value in preventing and treating diabetic
neuropathy, which is believed to be due in part to glycation and protein
oxidation by glucose (glycoxidation). Lipoic acid has been an approved
treatment for this condition in Germany for 25 years.
Aruoma OI, Laughton MJ and Halliwell B in 1989.
Biochim Biophys Acta 1999 Nov 16;1472(3):651-7
Hydrogen peroxide-mediated Cu,Zn-superoxide dismutase fragmentation:
protection by carnosine, homocarnosine and anserine.
Choi SY, Kwon HY, Kwon OB, Kang JH
Department of Genetic Engineering, Division of Life Sciences, Hallym
University, Chunchon, South Korea.
The fragmentation of human Cu,Zn-superoxide dismutase (SOD) was observed
during incubation with H(2)O(2). Hydroxyl
radical scavengers such as sodium azide, formate and mannitol protected the
fragmentation of Cu,Zn-SOD. These results
suggested that *OH was implicated in the hydrogen peroxide-mediated
Cu,Zn-SOD fragmentation. Carnosine, homocarnosine
and anserine have been proposed to act as anti-oxidants in vivo. We
investigated whether three compounds could protect the
fragmentation of Cu,Zn-SOD induced by H(2)O(2). The results showed that
carnosine, homocarnosine and anserine
significantly protected the fragmentation of Cu,Zn-SOD. All three compounds
also protected the loss of enzyme activity
induced by H(2)O(2). Carnosine, homocarnosine and anserine effectively
inhibited the formation of *OH by the
Cu,Zn-SOD/H(2)O(2) system. These results suggest that carnosine and related
compounds can protect the hydrogen
peroxide-mediated Cu,Zn-SOD fragmentation through the scavenging of *OH.
PMID: 10564779, UI: 20033431
Exp Gerontol 1999 Jan;34(1):35-45
Further evidence for the rejuvenating effects of the dipeptide L-carnosine
on cultured human diploid fibroblasts.
McFarland GA, Holliday R
CSIRO Division of Molecular Science, Sydney Laboratory, North Ryde,
We have confirmed and extended previous results on the beneficial effects of
L-carnosine on growth, morphology, and
longevity of cultured human fibroblasts, strains MRC-5 and HFF-1. We have
shown that late-passage HFF-1 cells retain a
juvenile appearance in medium containing 50 mM carnosine, and revert to a
senescent phenotype when carnosine is removed.
Switching cells between medium with and without carnosine also switches
their phenotype from senescent to juvenile, and the
reverse. The exact calculation of fibroblast lifespans in population
doublings (PDs) depends on the proportion of inoculated
cells that attach to their substrate and the final yield of cells in each
subculture. We have shown that carnosine does not affect
cell attachment, but does increase longevity in PDs. However, the plating
efficiency of MRC-5 cells seeded at low density is
strongly increased in young and senescent cells by carnosine, as shown by
the growth of individual colonies. We have also
demonstrated that very late-passage MRC-5 cells (with weekly change of
medium without subculture) remain attached to their
substrate much longer in medium containing carnosine in comparison to
control cultures, and also retain a much more normal
phenotype. Carnosine is a naturally occurring dipeptide present at high
concentration in a range of human tissues. We suggest it
has an important role in cellular homeostasis and maintenance.
PMID: 10197726, UI: 99211583
Cell Mol Neurobiol 1999 Feb;19(1):45-56
Carnosine: an endogenous neuroprotector in the ischemic brain.
Stvolinsky SL, Kukley ML, Dobrota D, Matejovicova M, Tkac I, Boldyrev AA
Institute of Neurology, Russian Academy of Medical Sciences, Moscow, Russia.
1. The biological effects of carnosine, a natural hydrophilic neuropeptide,
on the reactive oxygen species (ROS) pathological
generation are reviewed. 2. We describe direct antioxidant action observed
in the in vitro experiments. 3. Carnosine was found
to effect metabolism indirectly. These effects are reflected in ROS turnover
regulation and lipid peroxidation (LPO) processes.
4. During brain ischemia carnosine acts as a neuroprotector, contributing to
better cerebral blood flow restoration,
electroencephalography (EEG) normalization, decreased lactate accumulation,
and enzymatic protection against ROS. 5. The
data presented demonstrate that carnosine is a specific regulator of
essential metabolic pathways in neurons supporting brain
homeostasis under unfavorable conditions.
PMID: 10079964, UI: 99179700
Int J Biochem Cell Biol 1998 Aug;30(8):863-8
Carnosine, a protective, anti-ageing peptide?
Molecular Biology and Biophysics Group, King's College London, Strand, UK.
Carnosine (beta-alanyl-L-histidine) has protective functions additional to
anti-oxidant and free-radical scavenging roles. It
extends cultured human fibroblast life-span, kills transformed cells,
protects cells against aldehydes and an amyloid peptide
fragment and inhibits, in vitro, protein glycation (formation of
cross-links, carbonyl groups and AGEs) and DNA/protein
cross-linking. Carnosine is an aldehyde scavenger, a likely lipofuscin (age
pigment) precursor and possible modulator of
diabetic complications, atherosclerosis and Alzheimer's disease.
PMID: 9744078, UI: 98416741
FEBS Lett 1995 Aug 28;371(1):81-5
Non-enzymatic glycosylation of the dipeptide L-carnosine, a potential
Hipkiss AR, Michaelis J, Syrris P
Division of Biomolecular Engineering, CSIRO, North Ryde, NSW, Australia.
The dipeptide carnosine (beta-alanyl-L-histidine) was readily glycosylated
non-enzymatically upon incubation with the sugars
glucose, galactose, deoxyribose and the triose dihydroxyacetone. Carnosine
inhibited glycation of actyl-Lys-His-amide by
dihydroxyacetone and it protected alpha-crystallin, superoxide dismutase and
catalise against glycation and cross-linking
mediated by ribose, deoxyribose, dihydroxyacetone, dihydroxyacetone
phosphate and fructose. Unlike certain glycated amino
acids, glycated carnosine was non-mutagenic. The potential biological and
therapeutic significance of these observations are
PMID: 7664889, UI: 95394154 --Tom
All snipped from LEF
There's an article in the current (July) Scientific American which
presents an entirely different mechanism for age-related damage,
glycation of tissue proteins. At a minimum it seems there is much
more to aging than DNA damage...
Anthony Cerami of the Kenneth S. Warren Laboratories in Tarrytown,
N.Y., suspected some 30 years ago that sugar affects how the body ages,
based on observations of diabetics, who age rapidly. Sugars are an
essential source of energy, but once in circulation they can act as
molecular glue, attaching themselves to the amino groups in tissue
proteins and cross-linking them into hard yellow-brown compounds
known as advanced glycation end products, or AGEs.
Indeed, after years of bread, noodles and cakes, human tissues
inevitably become rigid and yellow with pigmented AGE deposits. For
the most part, piling on dark pigments in the teeth, bones and
skin is harmless. But where glucose forms tight bonds with the
long-lived protein collagen, the result is a constellation of changes,
including thickened arteries, stiff joints, feeble muscles and failing
organs--the hallmarks of a frail old age.
Cerami's team showed in the mid-1980s that aminoguanidine could keep
the tissues of diabetic rats and other old animals as elastic as those
of young control subjects. It boosted their cardiovascular function
and improved other age-related disorders. Further studies showed
that aminoguanidine lowered diabetics' urine albumin--an indicator
of kidney malfunction--and delayed AGE-related damage to the retina.
A single fountain-of-youth elixir is highly unlikely, says Tamara
Harris of the National Institute on Aging, because other activities,
such as free-radical oxidation and possibly telomere shortening,
also contribute to the body's slow decline. Moreover, AGE-related
research tends to be slow: Harris points out that there is no easy,
well-validated way to measure AGE in the body, a shortcoming that
complicates trials. To Harris, however, AGE breakers remain an
appealing option. "This is a nice approach because it is multifocal,
aimed at a basic process that occurs in multiple systems. But,"
she warns, "there won't be one silver bullet."
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