摘要:SummaryLiver aging impairs the ability of hepatocyte regeneration. Recent studies have found that oxytocin (OT) plays an important role in promoting tissue repair and maintaining differentiation and regeneration of stem cells. Here, we reported that OT receptors, which are specifically located in hepatocytes, decrease with aging in human and mice. Interestingly, the level of serum OT also decline with age. Notably, OT promotes hepatocyte regeneration only in aged mice but not in young micein vitroandin vivo. Further studies reveal that OT promotes autophagy in either AML12 mouse hepatocytes or aged mice after partial hepatectomy or with CCl4-induced acute liver injury. In conclusion, OT promotes liver regeneration, especially in aged mice, which may be achieved by promoting autophagy. All these results support the possibility of OT and its analog being a potent anti-aging drug and promote liver rejuvenation.Graphical abstractDisplay OmittedHighlights•The levels of oxytocin (OT) and its receptor OTR decrease with age•OT is a hepatotrophic factor for regeneration in aged liver•OT promotes hepatocyte autophagy in aged miceAge; molecular physiology; molecular biology; endocrinology