Carnosine is a multifunctional dipeptide made up of a chemical combination of the amino acids beta-alanine and l-histidine. Long-lived cells such as nerve cells (neurons) and muscle cells (myocytes) contain high levels of carnosine. Muscle levels of carnosine correlate with the maximum life spans of animal species (Hipkiss AR et al., 1995).Laboratory research on cellular senescence (the end of the life cycle of dividing cells) suggests that these facts may not be coincidences. Carnosine has the remarkable ability to rejuvenate cells approaching senescence, restoring normal appearance and extending cellular life span.
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The scientists switched late-passage fibroblasts back and forth several times between the culture media. They consistently observed that the carnosine culture medium restored the juvenile cell phenotype within days, whereas the standard culture medium brought back the senescent cell phenotype.
The carnosine medium also increased life span, even for old cells. The number of PDs, or population doublings, provides a convenient measure of cell division. When late-passage lung fibroblasts at 55 PDs (population doublings) were transferred to the carnosine medium, they lived to 69 to 70 PDs, compared to 57 to 61 PDs for the fibroblasts that were not transferred. Moreover, the fibroblasts transferred to the carnosine medium attained a life span of 413 days, compared to 126 to 139 days for the control fibroblasts. Carnosine increased chronological life span more dramatically than PDs in the Australian series of experiments.
When cells in the carnosine medium eventually enter into cellular senescence, they nevertheless retain a normal or less senescent morphology. Carnosine's ability to retain or restore the juvenile phenotype suggests that it may help maintain cellular homeostasis.
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Extending organism life span
Do carnosine's rejuvenating effects on cells extend to the entire organism? Similar anti-senescence effects have now been demonstrated in mice. A new Russian study tested the effect of carnosine on life span and indicators of senescence in senescence-accelerated mice (Yuneva MO et al., 1999; Boldyrev AA et al., 1999). Half the mice were given carnosine in their drinking water starting at two months of age. Carnosine extended the life span of the treated mice by 20% on average, compared to the mice not fed carnosine.
Carnosine did not alter the 15 month maximum life span of the senescence-accelerated mice strain, but it did significantly raise the number of mice surviving to old age. The mice given carnosine were about twice as likely to reach the ¡§ripe old age¡¨ of 12 months as untreated mice. It also improved indicators of senescence measured at the ¡§old age¡¨ of ten months.
Carnosine distinctly improved the appearance of the aged mice, whose coat fullness and color remained much closer to that of young animals. Significantly more carnosine-treated mice had glossy coats (44% vs. 5%), while significantly fewer had skin ulcers (14% vs. 36%). However, carnosine did not affect the loss or texture of hair. Carnosine significantly reduced the rates of spinal lordokyphosis (spinal curvature) and periopthalmic lesions, but did not affect corneal opacities.
The sharpest contrast between the treated and untreated mice was seen in their behavior. Only 9% of the untreated mice displayed normal behavioral reactivity, compared to 58% of the carnosine treated mice.
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Genome protection
DNA is organized into chromosomes, each of which contains a double helical DNA structure carrying the genes. Oxidative stress causes breaks and other aberrations in the chromosome that accumulate with age. A fascinating experiment shows the paradoxical effects of antioxidants on oxidative damage to chromosomes (Gille JJ et al., 1991). This study used hyperoxia, exposure to nearly pure oxygen (90%), as a physiologically natural oxidative stressor. Hyperoxia is thought to generate free radicals at the same intracellular sites where they normally form over time.
The scientists tested the ability of several antioxidants¡Xincluding vitamin C, n-acetylcysteine (NAC), vitamin E, carnosine and a form of glutathione¡Xto protect the chromosomes in Chinese hamster ovary cells from oxidative damage. Some of the antioxidants tested acted instead as pro-oxidants: they increased chromosomal damage, aggravating the effects of hyperoxia. It is a well known phenomenon that single antioxidants can sometimes exert a pro-oxidant effect in the body, which is the reason people take multiple antioxidants. In this study, only one antioxidant, carnosine, significantly reduced chromosomal damage. Cells cultured without any antioxidant exhibited 133 chromosomal aberrations per 100 cells. Carnosine reduced this level of damage by two-thirds, to only 44 chromosomal aberrations per 100 cells. Carnosine preserved 68% of cells fully intact, as compared to 46% of the control cells.
"It is not so much that you use your mind wrongly--you usually don't use it at all. It uses you. This is the disease." -Eckhart Tolle, The Power of Now
