Mesenchymal Stem Cell-Derived Exosomes Improve Aging-Related Changes in Liver Lipid Metabolism by Enhancing Autophagy.

Abstract

Health problems associated with aging have become increasingly severe in recent years. For example, hepatic lipid metabolism declines as the body ages, leading to lipid metabolic disorders. Although exosomes have been explored for treating metabolic diseases, there is currently a paucity of research regarding aging-related changes in hepatic lipid metabolism. Herein, we cultured human umbilical cord mesenchymal stem cells (HucMSCs), from which we extracted HucMSC-derived exosomes (HucMDEs). We then established a natural aging mouse model in vivo and a palmitic acid-induced AML12 cell model in vitro; HucMDEs were subsequently used as an intervention. Western blot analysis and quantitative real-time PCR were used to investigate changes in liver lipid metabolism and senescence-related markers in vivo and in vitro. Our results revealed that the HucMDE-injected mice showed reduced body weights, increased insulin sensitivity, decreased hepatic lipid deposition, reduced senescence, and augmented autophagy levels compared with the aged group of mice. The in vitro results were consistent with the in vivo results. When autophagy-related genes were silenced in AML12 cells via small interfering RNAs, or when cells were treated with the autophagy inhibitor 3-methyladenine or the lysosomal inhibitor bafilomycin A1, HucMDEs were able to reverse the reduction in hepatocyte autophagy levels. In this study, we demonstrated that HucMDEs improved hepatic lipid metabolism and attenuated cellular senescence by enhancing autophagy. We expect that these findings will provide novel potential therapeutic targets for the treatment of hepatic lipid metabolism disorders during aging.