Effect of Carnosine on Age-Induced Changes in Senescence-Accelerated Mice

Yuneva, M. O.; Bulygina, E. R.; Gallant, S.; Kramarenko, Galina G.; Stvolinsky, S. L.; Semyonova, M.L.; Boldyrev, A. A.

doi:10.1089/rej.1.1999.2.337

Cited by 43 publications

(20 citation statements)

References 8 publications

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“…In the brain, carnosine has been found in glial cells and in some type of neurons [266]; uptake of carnosine has been found to be mediated by a high affinity, energy-dependent dipeptide transport system, identified as the peptide transporter PepT2 [267]. Carnosine has been shown to delay ageing in cultured human fibroblasts [268], male Drosophila [269] and senescence-accelerated mice [270]. Therapeutic potential has also been invoked in cataractogenesis [271] and diabetes [272][273][274].…”

Section: Carnosinementioning

confidence: 99%

Cellular Stress Response: A Novel Target for Chemoprevention and Nutritional Neuroprotection in Aging, Neurodegenerative Disorders and Longevity

Calabrese

Cornelius

Mancuso³

et al. 2008

Neurochem Res

255

227

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The predominant molecular symptom of aging is the accumulation of altered gene products. Moreover, several conditions including protein, lipid or glucose oxidation disrupt redox homeostasis and lead to accumulation of unfolded or misfolded proteins in the aging brain. Alzheimer's and Parkinson's diseases or Friedreich ataxia are neurological diseases sharing, as a common denominator, production of abnormal proteins, mitochondrial dysfunction and oxidative stress, which contribute to the pathogenesis of these so called "protein conformational diseases". The central nervous system has evolved the conserved mechanism of unfolded protein response to cope with the accumulation of misfolded proteins. As one of the main intracellular redox systems involved in neuroprotection, the vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins (Hsp) Hsp70 and heme oxygenase-1, as well as thioredoxin reductase and sirtuins. Nutritional studies show that ageing in animals can be significantly influenced by dietary restriction. Thus, the impact of dietary factors on health and longevity is an increasingly appreciated area of research. Reducing energy intake by controlled caloric restriction or intermittent fasting increases lifespan and protects various tissues against disease. Genetics has revealed that ageing may be controlled by changes in intracellular NAD/NADH ratio regulating sirtuin, a group of proteins linked to aging, metabolism and stress tolerance in several organisms. Recent findings suggest that several phytochemicals exhibit biphasic dose responses on cells with low doses activating signaling pathways that result in increased expression of vitagenes encoding survival proteins, as in the case of the Keap1/Nrf2/ARE pathway activated by curcumin and NAD/NADH-sirtuin-1 activated by resveratrol. Consistently, the neuroprotective roles of dietary antioxidants including curcumin, acetyl-L-carnitine and carnosine have been demonstrated through the activation of these redox-sensitive intracellular pathways. Although the notion that stress proteins are neuroprotective is broadly accepted, still much work needs to be done in order to associate neuroprotection with specific pattern of stress responses. In this review the importance of vitagenes in the cellular stress response and the potential use of dietary antioxidants in the prevention and treatment of neurodegenerative disorders is discussed.

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Section: Carnosinementioning

confidence: 99%

Cellular Stress Response: A Novel Target for Chemoprevention and Nutritional Neuroprotection in Aging, Neurodegenerative Disorders and Longevity

Calabrese

Cornelius

Mancuso³

et al. 2008

Neurochem Res

255

227

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“…Amongst carnosine's enigmatic properties are its apparent anti-ageing actions; the dipeptide is one of a very few naturally-occurring compounds which suppresses cell senescence, induces rejuvenating effects Holliday, 1994 and, and protects against telomere shortening (Shao et al, 2004) in cultured human fibroblasts. The dipeptide also extends the life-span of senescence-accelerated mice (Yuneva et al, 1999) and Drosophila (Yuneva et al, 2002). There are many possible mechanisms by which carnosine exerts these anti-ageing actions however, some of which were summarized a decade ago (Hipkiss, 1998).…”

Section: Carnosine and Ageingmentioning

confidence: 99%

On the enigma of carnosine’s anti-ageing actions

Hipkiss¹

2009

Experimental Gerontology

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Carnosine ( -alanyl-L-histidine) has described as a forgotten and enigmatic dipeptide. Carnosine's enigma is particularly exemplified by its apparent anti-ageing actions; it suppresses cultured human fibroblast senescence and delays ageing in senescence-accelerated mice and Drosophila, but the mechanisms reponsible remain uncertain. In addition to carnosine's well-documented anti-oxidant, anti-glycating, aldehyde-scavenging and toxic metal-ion chelating properties, its ability to influence the metabolism of altered polypeptides, whose accumulation characterises the senescent phenotype, should also be considered. When added to cultured cells, carnosine was found in a recent study to suppress phosphorylation of the translational initiation factor eIF4E resulting in decreased translation frequency of certain mRNA species. Mutations in the gene coding for eIF4E in nemtodes extend organism lifespan, hence carnosine's anti-ageing effects may be a consequence of decreased error-protein synthesis which in turn lowers formation of protein carbonyls and increases protease availability for degradation of polypeptides altered postsynthetically. Other studies have revealed carnosine-induced upregulation of stress protein expression and nitric oxide synthesis, both of which may stimulate proteasomal elimination of altered proteins. Some anti-convulsants can enhance nematode longevity and suppress the effects of a protein repair defect in mice, and as carnosine exerts anti-convulsant effects in rodents, it is speculated that the dipeptide may participate in the repair of protein isoaspartyl groups. These new observations only add to the enigma of carnosine's real in vivo functions. More experimentation is clearly required. ACCEPTED MANUSCRIPT 3 Carnosine and ageing.The naturally-occurring dipeptide carnosine ( -alanyl-L-histidine) has been described as forgotten and enigmatic (Bauer, 2005): the present paper is an attempt to rectify the former opinion, but, however only adds to the latter view. Amongst carnosine's enigmatic properties are its apparent anti-ageing actions; the dipeptide is one of a very few naturally-occurring compounds which suppresses cell senescence, induces rejuvenating effects Holliday, 1994 and, and protects against telomere shortening (Shao et al., 2004) in cultured human fibroblasts. The dipeptide also extends the life-span of senescence-accelerated mice (Yuneva et al., 1999) and Drosophila (Yuneva et al., 2002). There are many possible mechanisms by which carnosine exerts these anti-ageing actions however, some of which were summarized a decade ago (Hipkiss, 1998). Meanwhile there have been a number of publications suggesting further possible routes by which carnosine could suppress

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“…In the same study carnosine extended the life span of the treated mice by 20% on average, compared to the control mice. 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 Yuneva et al, 1999).…”

Section: General Effects Of Carnosinementioning

confidence: 77%