2. Academic Validation
  3. Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1

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

  • Acta Pharm Sin B. 2024 Mar;14(3):1166-1186. doi: 10.1016/j.apsb.2023.12.009.
Shanshan Rao 1 2,  Zehui He 1 2,  Zun Wang 1 2 3,  Hao Yin 1 2,  Xiongke Hu 1 2 4,  Yijuan Tan 1 2,  Tengfei Wan 1 2,  Hao Zhu 1 2,  Yi Luo 1 2,  Xin Wang 1 2,  Hongming Li 1 2,  Zhenxing Wang 1 2,  Xinyue Hu 5,  Chungu Hong 1 2,  Yiyi Wang 1 2,  Mingjie Luo 3 6,  Wei Du 1 7,  Yuxuan Qian 1 2,  Siyuan Tang 3,  Hui Xie 1 2 8,  Chunyuan Chen 1 2
Affiliations

Affiliations

  • 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.
PMID: 38487008 DOI: 10.1016/j.apsb.2023.12.009
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.

Keywords

Anti-aging; Cellular senescence; Extracellular vesicles; Natural aging mice; PLAU; Senescence-accelerated mice; TIMP1; Urine-derived stem cells.

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