Stress-stimulated epinephrine induces premature senescence in dermal fibroblasts and contributes to impaired skin wound healing.

External factors accelerate cellular senescence in the skin and compromise its repair process. Psychological stress impairs skin wound healing, but no study examined its role in cellular senescence during skin tissue repair. Thus, this study evaluated the effect of stress on cellular senescence during skin wound healing. Human dermal fibroblasts (HDFs) and human skin from aged and young donors were treated with a non-lethal dose of epinephrine or hydrogen peroxide following a stress-induced premature senescence protocol. In vitro, epinephrine or hydrogen peroxide promoted the expression of senescence-associated β-galactosidase, p53, and notch target gene hairy and enhancer of split 1 (HES1) in HDFs, confirming the induction of premature senescence. A higher expression of matrix metalloproteinase-9 and interleukin-8 was observed in HDFs incubated with epinephrine or hydrogen peroxide, confirming a pro-inflammatory senescence-associated secretory phenotype. The protein levels of silent information regulator sirtuin 1, which is associated with a longer lifespan, were not changed in HDFs submitted to stressful conditions. In ex vivo experiments, epinephrine administration impaired wound closure and increased HES1 expression in aged human skin. In conclusion, stress-induced high epinephrine level induced premature senescence in HDFs, which contributes to impaired wound healing in young and aged skin.