mTORC1-Induced Bone Marrow-Derived Mesenchymal Stem Cell Exhaustion Contributes to the Bone Abnormalities in Klotho-Deficient Mice of Premature Aging

• DOI: 10.1089/scd.2022.0243
• Publication Date: 2023-03-16T09:42:12Z
• Authors: Ran Feng; Su Wu; Ruofei Li; Kunling Huang; Ting Zeng; Zhifen Zhou; Xiaoqin Zhong; Zhou Songyang; Feng Liu
• Keywords: Klotho

Stem cell exhaustion is a hallmark of aging. Klotho-deficient mice (kl/kl mice) murine model that mimics human aging with significant bone abnormalities. The aim this study using kl/kl to investigate the functional change marrow-derived mesenchymal stem cells (BMSCs) and explore underlying mechanism. We found klotho deficiency leads In addition, BMSCs manifested hyperactive proliferation but functionally declined both in vivo vitro. Mammalian target rapamycin complex 1 (mTORC1) activity was higher freshly isolated BMSCs, autophagy significantly decreased, possibly through mTORC1 activation. Conditional medium containing soluble Klotho protein (sKL) rescued hyperproliferation by inhibiting restoring autophagy. Finally, intraperitoneal injection inhibitor restored BMSC quiescence, ameliorated phenotype, increased life span vivo. This research highlights therapeutic strategy maintain homeostasis adult pool for healthy