近日，中国科学院生物物理所姬广聚等研究人员合作发现，外泌体miR-302b通过逆转衰老细胞的增殖停滞来使衰老小鼠年轻化。该研究于2025年1月15日在线发表于国际一流学术期刊《细胞—代谢》。

研究人员展示了人类胚胎干细胞衍生的外泌体（hESC-Exo），通过恢复衰老细胞（SnC）的增殖能力，逆转了衰老。在衰老小鼠中，hESC-Exo治疗重塑了SnC的增殖景观，导致年轻化，表现为延长寿命、改善身体表现和减少衰老标志物。

Ago2 Clip-seq分析识别了富含于hESC-Exo中的miR-302b，它特异性地靶向细胞周期抑制因子Cdkn1a和Ccng2。此外，miR-302b治疗逆转了SnC在体内的增殖停滞，导致年轻化，且在24个月的观察期内没有安全性问题。

这些发现表明，外泌体miR-302b具有逆转细胞衰老的潜力，为缓解衰老相关病理和衰老提供了有前景的方法。

据介绍，细胞衰老是衰老的标志，涉及稳定地退出细胞周期。SnC与衰老及衰老相关疾病密切相关，因此它们成为抗衰老干预的潜在靶点。

附：英文原文

Title: Exosomal miR-302b rejuvenates aging mice by reversing the proliferative arrest of senescent cells

Author: Youkun Bi, Xinlong Qiao, Zhaokui Cai, Hailian Zhao, Rong Ye, Qun Liu, Lin Gao, Yingqi Liu, Bo Liang, Yixuan Liu, Yaning Zhang, Zhiguang Yang, Yanyun Wu, Huiwen Wang, Wei Jia, Changqing Zeng, Ce Jia, Hongjin Wu, Yuanchao Xue, Guangju Ji

Issue&Volume: 2025-01-15

Abstract: Cellular senescence, a hallmark of aging, involves a stable exit from the cell cycle. Senescent cells (SnCs) are closely associated with aging and aging-related disorders, making them potential targets for anti-aging interventions. In this study, we demonstrated that human embryonic stem cell-derived exosomes (hESC-Exos) reversed senescence by restoring the proliferative capacity of SnCs in vitro. In aging mice, hESC-Exos treatment remodeled the proliferative landscape of SnCs, leading to rejuvenation, as evidenced by extended lifespan, improved physical performance, and reduced aging markers. Ago2 Clip-seq analysis identified miR-302b enriched in hESC-Exos that specifically targeted the cell cycle inhibitors Cdkn1a and Ccng2. Furthermore, miR-302b treatment reversed the proliferative arrest of SnCs in vivo, resulting in rejuvenation without safety concerns over a 24-month observation period. These findings demonstrate that exosomal miR-302b has the potential to reverse cellular senescence, offering a promising approach to mitigate senescence-related pathologies and aging.

DOI: 10.1016/j.cmet.2024.11.013

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00481-9