Bioenergetic analysis of aged‐phenotype skin in a rare syndromic cutis laxa

Abstract

Skin aging is an inevitable phenomenon characterized by wrinkled skin and loss of elasticity. To date, several studies have been performed on skin aging to discover the underlying mechanisms and improve efficient preventive strategies and anti-aging therapeutics. Here, we aimed to investigate the modifications of oxidative phosphorylation and glycolysis which are the critical determinants of aging in aged-phenotype skin. Due to the complexity of the skin aging process, we performed bioenergetic measurements on aged-phenotype fibroblasts from an inherited cutis laxa syndrome which remarkably presents clinical features of normal aged skin. Bioenergetic analysis was performed on cutis laxa samples (n=3) and healthy samples (n=3) using Seahorse XFe24 Analyzer. We also compared the sensitivity of cultured aged-phenotype fibroblasts to normal cells in glucose withdrawal. Our results show a significant increase in oxidative phosphorylation parameters but not glycolysis in the patient fibroblast cells implying increased energy demand and preferential dependence on mitochondrial respiration in those cells. Interestingly, we found the patient cells demonstrate hypersensitivity to glucose starvation, supporting their enhanced energy consumption. In summary, our work suggested increased energy demand and higher oxidative phosphorylation in aged-phenotype cells which can be considered in anti-skin aging therapeutic design.