l-histidine and l-carnosine accelerate wound healing via regulation of corticosterone and PI3K/Akt phosphorylation in d-galactose-induced aging models in vitro and in vivo

Abstract

Abstract Impaired skin wound healing in the elderly can lead to medical issues and increased mortality. Although l -histidine and l -carnosine are potent anti-aging amino acids, the wound healing effects of these amino acids in aging remain to be elucidated. Here, we investigated the regenerative potential of l -histidine and l -carnosine in in vitro and in vivo aging models. l -histidine (1\u202fmM), l -carnosine (10\u202fmM), or a combination improved proliferation, migration, senescence, and epithelial-mesenchymal transition (EMT) in d -galactose-induced aged keratinocytes. An in vivo mouse aging model was established with injection of d -galactose (s.c. 500\u202fmg/kg) daily for eight weeks. Supplementation with l -histidine (2\u202fg/L), l -carnosine (2\u202fg/L), or a combination improved collagen and wound healing with EMT markers, E-cadherin, N-cadherin, and MMP-2. These effects were concomitant with reduced circulating levels of corticosterone and increased PI3K/Akt phosphorylation. These results suggest that l -histidine and l -carnosine have the potential to facilitate wound healing in aging skin.