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Carnosine as a dietary component and its effect on aging, cortisol and depression

According to the latest research , carnosine can not only slow down various physiological processes in the body related to cellular senescence (aging)m), but is also able to slow down many of the harmful biochemical phenomena thought to be associated with the formation of the old phenotype.

A scientific study on the effects of oral administration of orodispersible levo-carnosine on quality of life [1] presents that supplementationsupplementation of the human diet with carnosine (β-alanyl-L-histidine), a naturally occurring neurobiological peptide, may have beneficial effects on physical activity and quality of life. A study on Telomere length and cortisol reactivity in children of depressed mothers [2] showed that major depressiondepressive disorder (MDD) is associated with reduced telomere length, increased susceptibility to dysfunction arehanging with age, and elevated cortisol levels in response to stress, while two other studies have described an association between reduced leukocyte telomere length and stress-related disorders [3,4]. The results of these scientific works are to suggest that carnosine insufficiency could cause a link between stress and depression-related phenomena and age-related dysfunction. Carnosine may present therapeutic potential for the treatment of depression and stress disorders if administered as a dietary supplement.

Carnosine and ageing

The highest concentrations of carnosine are found in the brain and muscles. In the brain carnosine is synthesized and secreted from astrocytes: it is degraded to its amino acid component by either cellular carnosinase (CNDP1) or serum carnosinase (CNDP2), the activity of which in the brain may increase in old age [5]. Carnosine and related peptides such as anserine and packin can also be obtained by eating dark meat, so they are absent in a strict vegetarian diet. Although carnosine was discovered more than a century ago [6], we are still not aware ofWe are not aware of all its effects, which is why this dipeptide has been described as “full of mystery” [7]. Evidence from animal studies suggests that carnosine is multifunctional. Cell culture studies show that carnosine can inhibit the growth of transformed cells [8,9,10], delay cell senescence [11], help maintain telomere length [12], and promote the formation of a more youthful phenotype when added to senescent cells [11]. Carnosine can inhibit many of the deleterious biochemical events thought to be associated with the formation of the senescent phenotype, which include Protein damage (including cross-linking [13]) induced by reactive oxygen species [14]), reactive nitrogen species
[15,16], reducing sugars [13], and reactive carbonyl species such as malondialdehyde [17], 4-hydroxynonenal [18,19], and methylglyoxal [20]. Animal model studies indicate beneficial effects of dipeptide on a number of age-related physiological conditions, including improvedwound healing [21,22], Alzheimer’s disease [23,24], Parkinson’s disease [25,26], stroke [27,28], atherosclerosis [29,30], cataracts [31,32], and diabetic kidney disease.

Depression, cortisol, aging and carnosine

The work by Gotlib et al [2] shows a relationship between telomere length, serum cortisol levels and depression in women. It has been suggested that patients with major depressive disorder (MDD) have an increased predisposition to develop a number of age-related disorders [see 2 and refs. therein for a fuller discussion]. The work of Miller and Sadeh [3] and Shaleh et al [4] detail the relationship between telomere erosion and stress-related depressive disorders. The nature of the relationship between cortisol levels, depression, telomere length, and aging, is not clear. It has been suggested that there is a common molecular entity whose activities link aging, telomeres, cortisol, and behavior. Carnosine may provide a therapeutic link between these phenomena because, as noted above, carnosine

(i) may act as an anti-aging agent (mimicking rapamycin), including beneficial effects in animal models of age-related brain dysfunction [23,24,25,26 , 27,28].
(ii) May help maintain telomere length [12],
iii), may increase cortisol metabolism – at least in mice [36].
iv) Ameliorates stress-induced changes in metabolism in mice [37]
v) and, when complexed with zinc, suppresses the effects of cortisol on rat bone metabolism [38].

The anti-stress effects of carnosine in mice are thought to be mediated by modulation of the stress-activated hypothalamic-pituitary-adrenal axis [37], while it has been shown to increaseelevated levels of cortisol are present in the cerebrospinal fluid of Alzheimer’s disease patients, which likely arise from dysregulation of the hypothalamic-pituitary-adrenal axis [39]. These observations suggest a possible role for carnosine in the control of age-related neurological dysfunction through effects on the hypothalamic-pituitary-adrenal axis in the human brain.

Carnosine supplementation affects brain function in chickens, rodents and humans

Carnosine supplementation can affect behaviour in chickens [40] and rodents [41,42]; its ability to suppress anxiety in rats [42] is probably due to increased cortisol metabolism [36]. Interestingly, it has also been reported that carnosine (β-alanyl-histidine) and its reverse structure (i.e. i.e., histidinyl-β-alanine) have opposite behavioral effects in chickens [40,43].

In humans, carnosine supplementation has been found to improve cognition or well-being in at least five studies [1,44,45,46,47]. Dietary supplementation with carnosine had beneficial effects on behavior in children with autism spectrum disorders [44] and improvedimproved cognitive function in patients suffering from Gulf War illness [45], schizophrenia [46], and chronic heart failure [1]. Another group also reported significant improvements in their quality of life [1]. A recent study showed that carnosine supplementation along with anserine improved cognitive function and physical capacity in the elderly [47]. These findings provide evidence that carnosine supplementation has therapeutic potential in humans, despite the occasionalthe presence of carnosinase, which might be expected to counteract any efficacy that the dipeptide might elicit. However, elevated levels of renal carnosinase have been shown to increase the likelihood of diabetic kidney disease in type 2 diabetics [34], which is likely due to increased destruction of the dipeptide. The fact that beneficial effects of carnosine supplementation have been found in humans [1,44,45,46,47] suggests that carnosinase activity is not necessarily a barrier to dipeptide efficacy.

Conclusion

The ability of carnosine to positively influence behavior in humans when present as a dietary supplement supports the idea that carnosine should be investigated for its therapeutic potential in the management of depression and post-traumatic stress disorder, as well as in the control of many age-related pathologies, despite the presence of carnosinase. However, it might be expected that genetically determined differences in carnosinase activity may influence whatany beneficial effects of carnosine that have been observed in the context of diabetic kidney disease [5,33,34].

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