Oxytocin Promotes Hepatic Regeneration in Elderly Mice

Organ aging is an irresistible natural law, which also happens in the liver. Liver aging leads to dysfunction of hepatic metabolism, impairs the ability of hepatocyte regeneration, and increases the incidence of liver diseases. Recent studies have found that oxytocin (OT) is an age-specific circulating hormone which plays an important role in promoting tissue repair and maintaining differentiation and regeneration of stem cells. Here we reported that OT receptors (OTRs), which is specifically located in hepatocytes, decreases with aging in human and mice. Interestingly, the level of serum OT also decline with age. In vitro experiments show that OT promotes the hepatocytes proliferation of AML 12 and the growth of hepatic organoids in mice. The in vivo studies show that OT promote liver regeneration only in aged mice but not in young mice. Further studies reveal that OT promotes autophagy in either AML12 mouse hepatocytes or aged mice after partial hepatectomy or CCl4-induced mouse model. 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. Funding Statement: This work was supported by grants from National Key Research and Development Program of China (2016YFC1302203), Taishan Scholars Program and Shandong Key Research and Development Program (2017GSF218032, 2019GSF108012). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: The experimental procedures on these mice were approved by the Medical Ethics Committee of Shandong University.