Treatment of Skin Aging and Photoaging with Innovative Oral Dosage Forms of Non-Hydrolized Carnosine and Carcinine

Aging is a multifactorial process resulting in several functional and esthetic changes in the skin. Advances in research have yielded a tremendous amount of information on the molecular pathways involved in both intrinsic aging (natural) and extrinsic aging (including photoaging). Some of the characteristic features of aging skin, such as wrinkling, loss of elasticity, and atrophy, can largely be attributed to dermal changes. The amount of collagen in the skin decreases, while the cross linking increases, and the solubility of collagen is reduced. The role of fibroblasts in aging tissue has been most extensively studied in mammalian skin. The total number of fibroblasts decreases, and their metabolism shows characteristic alterations.The dermis is maintained in large part by fibroblasts, which secrete dermal collagens, elastin, and other extracellular matrix components. When the skin is wounded, fibroblasts secrete proteases to degrade the wounded matrix, and then synthesize new matrix. The fibroblasts also secrete growth factors to stimulate the keratinocytes to proliferate and close the wound and cytokines to attract macrophages to engulf and degrade debris. Stress-induced premature senescence (SIPS) occurs after many different sublethal stresses including a number of oxidation factors, such as H2 O2 , hyperoxia, or organic and lipid hydroperoxides. Fibroblast cells in replicative senescence share common features with cells in SIPS: morphology, senescence-associated beta-galactosidase activity, cell cycle regulation, gene expression and telomere shortening. Most human cells lack sufficient telomerase to maintain telomeres, hence these genetic elements shorten with time and stress, contributing to aging and disease. We systematically examine the evidence supporting the use of dosage forms of non-hydrolized carnosine or carcinine in oral formulations for skin beautification purposes and provide a summary of the biomarkers of intrinsic and extrinsic skin aging, including photoaging. Senescence phenotype of human diploid fibroblasts is related with the exhaustion of their proliferative potential. This work suggests that different cell types, such as human skin fibroblasts, may use specific cellular treatment strategies with imidazole-containing dipeptides to halt the accelerated senescence of the fibroblast cells in response to telomere attrition and thus prevent skin aging through the number of biologically viable and safe metabolic pathways. The published data demonstrate that telomerase is expressed in the epidermis in situ independent of age. The reason for the sustained telomere length or expression of telomerase activity in the epidermis is associated not only with an increased turnover of keratinocytes, but also occurs due to the fact that the formation of a well structured epidermis strictly depends on a tight balance between proliferation and differentiation. Oral dosage forms of non-hydrolized carnosine or carcinine induce cellular responses in human skin fibroblasts through the telomere-mediated pathway and redox signaling, supporting the view that carnosine or related imidazole-containing dipeptide based compound-induced hormetic stimulation of cellular antioxidant defenses can be a useful approach toward anti-aging intervention to the skin.