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

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 mM), L-carnosine (10 mM), or a combination improved proliferation, migration, senescence, and epithelial-mesenchymal transition (EMT) in o-galactose-induced aged keratinocytes. An in vivo mouse aging model was established with injection of D-galactose (s.c. 500 mg/kg) daily for eight weeks. Supplementation with L-histidine (2 g/L), L-carnosine (2 g/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.