Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1  

作　　者：Shanshan Rao Zehui He Zun Wang Hao Yin Xiongke Hu Yijuan Tan Tengfei Wan Hao Zhu Yi Luo Xin Wang Hongming Li Zhenxing Wang Xinyue Hu Chungu Hong Yiyi Wang Mingjie Luo Wei Du Yuxuan Qian Siyuan Tang Hui Xie Chunyuan Chen 

机构地区：[1]Department of Orthopedics,Movement System Injury and Repair Research Center,Xiangya Hospital,Central South University,Changsha 410008,China [2]Hunan Key Laboratory of Angmedicine,Changsha 410008,China [3]Xiangya School of Nursing,Central South University,Changsha 410013,China [4]Department of Pediatric Orthopedics,Hunan Children’s Hospital,University of South China,Changsha 410007,China [5]Department of Respiratory Medicine,Xiangya Hospital,Central South University,Changsha 410008,China [6]School of Nursing,Xinjiang Medical University,Urumqi,Xinjiang 830000,China [7]Department of Rehabilitation,Xiangya Hospital,Central South University,Changsha 410008,China [8]National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South University,Changsha 410008,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第3期1166-1186,共21页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.82125023,82072504,81871822,82172501,81801395,and 82200039);the Science and Technology Innovation Program of Hunan Province(Grant Nos.2020RC4008 and 2022RC1211,China);the China National Postdoctoral Program for Innovative Talents(Grant No.BX2021383,China);the Central South University InnovationDriven Research Programme(Grant Nos.2023CXQD001 and 2019CX014,China);the Hunan Province Natural Science Foundation of China(Grant Nos.2023JJ10094 and 2020JJ5883);the Youth Science Foundation of Xiangya Hospital(Grant No.2022Q07,China);the Hunan Provincial Innovation Foundation for Postgraduate(Grant Nos.2021ZZTS0342 and 2022ZZTS0239,China)。

摘　　要：Aging increases the risks of various diseases and the vulnerability to death.Cellular senescence is a hallmark of aging that contributes greatly to aging and aging-related diseases.This study demonstrates that extracellular vesicles from human urine-derived stem cells(USC-EVs)efficiently inhibit cellular senescence in vitro and in vivo.The intravenous injection of USC-EVs improves cognitive function,increases physical fitness and bone quality,and alleviates aging-related structural changes in different organs of senescence-accelerated mice and natural aging mice.The anti-aging effects of USC-EVs are not obviously affected by the USC donors’ages,genders,or health status.Proteomic analysis reveals that USC-EVs are enriched with plasminogen activator urokinase(PLAU)and tissue inhibitor of metalloproteinases 1(TIMP1).These two proteins contribute importantly to the anti-senescent effects of USC-EVs associated with the inhibition of matrix metalloproteinases,cyclin-dependent kinase inhibitor 2A(P16INK4a),and cyclin-dependent kinase inhibitor 1A(P21cip1).These findings suggest a great potential of autologous USC-EVs as a promising anti-aging agent by transferring PLAU and TIMP1 proteins.

关 键 词：Extracellular vesicles Urine-derived stem cells Cellular senescence ANTI-AGING PLAU TIMP1 Senescence-accelerated mice Natural aging mice 

分 类 号：R965[医药卫生—药理学]