Oxytocin alleviates cellular senescence through oxytocin receptor-mediated extracellular signal-regulated kinase/Nrf2 signalling.

Our findings bring to light the role of OT in the prevention of skin ageing, which might allow development of new clinical strategies. What's already known about this topic? Senescent keratinocytes and fibroblasts accumulate with age in the skin and contribute to the loss of skin function and integrity during ageing. Senescent cells secrete senescence-associated secretory phenotype (SASP), which includes the release of proinflammatory cytokines such as interleukin (IL)-6 and IL-1, chemokines, extracellular matrix-remodelling proteases and growth factors. The neuropeptide oxytocin (OT) and its receptor (OXTR) have protective effects against various age-related disorders. What does this study add? OT suppressed SASP-induced cellular senescence in normal human dermal fibroblasts (NHDFs), depending on the age of the NHDFs' donor. The inhibitory effects of OT on cellular senescence required OXTR-mediated phosphorylation of extracellular signal-regulated kinase, which enhanced nuclear localization of Nrf2, a vital factor in the antioxidant defence system. The age-specific antisenescent effects of OT were closely related to hypermethylation of OXTR. What is the translational message? Our results suggest that OT and OXTR agonists could be clinically promising agents for the improvement of age-associated skin ageing, especially in women.