Life Extension Magazine

Life Extension Magazine June 2012

Abstracts

Carnosine

Carnosine in patients with type I diabetes mellitus.

Examination of carnosine in patients with diabetes mellitus type I, showed that the plasma levels of carnitine were non significantly increased compared to the levels in healthy population, while the levels in red cells were decreased Lowered levels of carnosine in red cells could point out similar deficit in other cells. Due to low levels in cells carnosine is less available for metabolic processes, like antioxidant reactions and its participation in antioxidants defense reactions is limited non-enzymatic glycosylation of proteins. Therefore it should be supplemented.

Bratisl Lek Listy. 1999 Sep;100(9):500-2

Retardation of the senescence of cultured human diploid fibroblasts by carnosine.

We have examined the effects of the naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) on the growth, morphology, and life span of cultured human diploid fibroblasts. With human foreskin cells, HFF-1, and fetal lung cells, MRC-5, we have shown that carnosine at high concentrations (20-50 mM) in standard medium retards senescence and rejuvenates senescent cultures. These late-passage cultures preserve a nonsenescent morphology in the presence of carnosine, in comparison to the senescent morphology first described by Hayflick and Moorhead. Transfer of these late-passage cells in medium containing carnosine to unsupplemented normal medium results in the appearance of the senescent phenotype. The serial subculture of cells in the presence of carnosine does not prevent the Hayflick limit to growth, although the life span in population doublings as well as chronological age is often increased. This effect is obscured by the normal variability of human fibroblast life spans, which we have confirmed. Transfer of cells approaching senescence in normal medium to medium supplemented with carnosine rejuvenates the cells but the extension in life span is variable. Neither D-carnosine, (beta-alanyl-D-histidine), homocarnosine, anserine, nor beta-alanine had the same effects as carnosine on human fibroblasts. Carnosine is an antioxidant, but it is more likely that it preserves cellular integrity by its effects on protein metabolism.

Exp Cell Res. 1994 Jun;212(2):167-75

Further evidence for the rejuvenating effects of the dipeptide L-carnosine on cultured human diploid fibroblasts.

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 life spans 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.

Exp Gerontol. 1999 Jan;34(1):35-45

Effect of carnosine on Drosophila melanogaster life span.

A positive dose-dependent effect of carnosine (beta-alanyl-L-histidine) on the life span of male Drosophila melanogaster flies was shown. The mean life span of male flies receiving 200 mg/liter carnosine approached that of females. At the same time carnosine had no effect on the life span of female flies. This positive effect of carnosine probably reflects its protective action against age-related accumulation of free radicals and did not depend on carnosine metabolism in the body. Addition of 200 mg/liter histidine and beta-alanine (separately or in combination) had no effect on the mean life span of flies.

Bull Exp Biol Med. 2002 Jun;133(6):559-61

Effect of carnosine and its Trolox-modified derivatives on life span of Drosophila melanogaster.

This study investigated the effect of antioxidants, i.e., carnosine and its Trolox- (water-soluble analog of alpha-tocopherol) acylated derivatives (S,S)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carbonyl-beta-alanyl-L-histidine (S,S-Trolox-carnosine, STC) and (R,S)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carbonyl-beta-alanyl-L-histidine (R,S-Trolox-carnosine, RTC) on the life span of the fruit fly Drosophila melanogaster. Adding carnosine to foodstuff was accompanied and followed by a 20% increase in the average life span of males, but it did not influence the average life span of females. At the same time, adding STC to foodstuff prolonged average longevity both in males (by 16%) and females (by 36%), but the addition of RTC to foodstuff had no influence upon the average life span of insects of either gender. The compounds studied have previously been shown to protect neurons of the rat brain from oxidative stress in the descending order of efficiency: RTC > STC > carnosine. The finding obtained in the present study suggests another order of efficacy regarding the effect on life span in male insects: STC > carnosine > RTC (inefficient). No correlation between antioxidant protection of rat neurons and the effect on life span of the fruit fly makes it possible to suppose the presence of additional cellular targets to be acted upon by exposure of D. melanogaster to these compounds.

Rejuvenation Res. 2010 Aug;13(4):453-7

Carnosine, the protective, anti-aging peptide.

Carnosine attenuates the development of senile features when used as a supplement to a standard diet of senescence accelerated mice (SAM). Its effect is apparent on physical and behavioral parameters and on average life span. Carnosine has a similar effect on mice of the control strain, but this is less pronounced due to the non-accelerated character of their senescence processes.

Biosci Rep. 1999 Dec;19(6):581-7

Carnosine as a potential anti-senescence drug.

The naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) has been found to exert an anti-senescence effect when used as a dietary supplement. Carnosine clearly improved the external appearance of experimental animals and provided beneficial physiological effects, thus maintaining the animals in better condition than control animals receiving no carnosine or a mixture of beta-alanine and L-histidine.

Biochemistry (Mosc). 2000 Jul;65(7):866-8

Carnosine is neuroprotective against permanent focal cerebral ischemia in mice.

BACKGROUND AND PURPOSE: Carnosine is a naturally occurring dipeptide with multiple neuroprotective properties. In addition, it is well tolerated in high doses with minimal side effects. The purposes of this study were to determine whether carnosine is neuroprotective in permanent focal cerebral ischemia and to determine potential mechanisms of neuroprotection.METHODS: We investigated the efficacy of carnosine in a mouse model of permanent focal cerebral ischemia. The effects of carnosine were investigated with respect to neuronal damage and infarct formation, endogenous antioxidant status, and matrix metalloproteinase activity. RESULTS: Carnosine significantly decreased infarct size and neuronal damage when administered at time points both before and after the induction of ischemia. Carnosine also decreased reactive oxygen species levels in the ischemic brain, preserved normal glutathione levels, and decreased matrix metalloproteinase protein levels and activity. CONCLUSIONS: Carnosine is neuroprotective in focal cerebral ischemia and appears to influence deleterious pathological processes that are activated after the onset of ischemia.

Stroke. 2007 Nov;38(11):3023-31

Protective effects of carnosine against malondialdehyde-induced toxicity towards cultured rat brain endothelial cells.

Malondialdehyde (MDA) is a deleterious end-product of lipid peroxidation. The naturally-occurring dipeptide carnosine (beta-alanyl-L-histidine) is found in brain and innervated tissues at concentrations up to 20 mM. Recent studies have shown that carnosine can protect proteins against cross-linking mediated by aldehyde-containing sugars and glycolytic intermediates. Here we have investigated whether carnosine is protective against malondialdehyde-induced protein damage and cellular toxicity. The results show that carnosine can (1) protect cultured rat brain endothelial cells against MDA-induced toxicity and (2) inhibit MDA-induced protein modification (formation of cross-links and carbonyl groups).

Neurosci Lett. 1997 Dec 5;238(3):135-8

Carnosine and its constituents inhibit glycation of low-density lipoproteins that promotes foam cell formation in vitro.

Glycation of low-density lipoprotein (LDL) by reactive aldehydes, such as glycolaldehyde, can result in the cellular accumulation of cholesterol in macrophages. In this study, it is shown that carnosine, or its constituent amino acids beta-alanine and l-histidine, can inhibit the modification of LDL by glycolaldehyde when present at equimolar concentrations to the modifying agent. This protective effect was accompanied by inhibition of cholesterol and cholesteryl ester accumulation in human monocyte-derived macrophages incubated with the glycated LDL. Thus, carnosine and its constituent amino acids may have therapeutic potential in preventing diabetes-induced atherosclerosis.

FEBS Lett. 2007 Mar 6;581(5):1067-70