Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1
Shan‐Shan Rao, Zehui He, Zun Wang, Hao Yin, Xiong‐Ke Hu, Yi‐Juan Tan, Tengfei Wan, Hao Zhu, Yi Luo, Xin Wang, Hongmin Li, Zhen‐Xing Wang, Xinyue Hu, Chun‐Gu Hong, Yiyi Wang, Mingjie Luo, Wei Du, Yuxuan Qian, Siyuan Tang, Hui Xie, Chun‐Yuan Chen
Abstract
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.