2. Academic Validation
  3. Delivering miR-23b-3p by small extracellular vesicles to promote cell senescence and aberrant lipid metabolism

Delivering miR-23b-3p by small extracellular vesicles to promote cell senescence and aberrant lipid metabolism

  • BMC Biol. 2025 Feb 11;23(1):41. doi: 10.1186/s12915-025-02143-9.
Ye Jin # 1 2,  Gaoge Sun # 3,  Binxian Chen # 1 4,  Siqin Feng # 5,  Muyun Tang # 5,  Hui Wang 6,  Ying Zhang 3,  Yuan Wang 7,  Yang An 8,  Yu Xiao 3 9 10 11,  Zihan Liu 3,  Peng Liu 12,  Zhuang Tian 13,  Hang Yin 14 15 16,  Shuyang Zhang 17 18 19,  Xiaodong Luan 20 21
Affiliations

Affiliations

  • 1 Rare Disease Medical Center, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China.
  • 2 Center for Digital Medicine and Artificial Intelligence, National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China.
  • 3 School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.
  • 4 School of Medicine, Tsinghua University, Beijing, 100084, China.
  • 5 Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China.
  • 6 Department of Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China.
  • 7 Echo Biotech Co., Ltd, Beijing, 102627, China.
  • 8 GemPharmatech Co., Ltd, Nanjing, 210000, China.
  • 9 Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, 100084, China.
  • 10 Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, 100084, China.
  • 11 Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510260, China.
  • 12 Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China.
  • 13 Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China. tianzhuangcn@sina.com.
  • 14 School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China. yin_hang@tsinghua.edu.cn.
  • 15 Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, 100084, China. yin_hang@tsinghua.edu.cn.
  • 16 Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, 100084, China. yin_hang@tsinghua.edu.cn.
  • 17 Rare Disease Medical Center, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China. shuyangzhang103@nrdrs.org.
  • 18 School of Medicine, Tsinghua University, Beijing, 100084, China. shuyangzhang103@nrdrs.org.
  • 19 Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China. shuyangzhang103@nrdrs.org.
  • 20 Rare Disease Medical Center, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China. luanxiaodong@pumch.cn.
  • 21 Center for Drug Research and Evaluation, National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, China. luanxiaodong@pumch.cn.
  • # Contributed equally.
PMID: 39934790 DOI: 10.1186/s12915-025-02143-9
Abstract

Background: Aging is a natural process that affects the majority of organs within the organism. The liver, however, plays a pivotal role in maintaining the organism's homeostasis due to its robust regenerative and metabolic capabilities. Nevertheless, the liver also undergoes the effects of aging, which can result in a range of metabolic disorders. The function of extracellular vesicles and the signals they convey represent a significant area of interest within the field of ageing research. However, research on liver ageing from the perspective of EVs remains relatively limited.

Results: In the present study, we extracted liver tissue small extracellular vesicles (sEVs) of mice at different ages and performed transcriptome and proteome analyses to investigate the senescence-associated secretory phenotype (SASP) and mechanisms. sEVs in the older group were rich in miR-23b-3p, which was abundant in the sEVs of induced aging cells and promoted cell senescence by targeting TNF alpha induced protein 3 (Tnfaip3). After injecting adeno-associated virus (AAV) expressing miR-23b-3p into mice, the liver of mice in the experimental group displayed a more evident inflammatory response than that in the control group. Additionally, we found elevated miR-23b-3p in blood-derived-sEVs from patients with familial hypercholesterolemia.

Conclusions: Our findings suggest that miR-23b-3p plays a pivotal role in liver aging and is associated with abnormal lipid metabolism. The upregulation of miR-23b-3p in liver EVs may serve as a potential biomarker for aging and metabolic disorders. Targeting miR-23b-3p could provide new therapeutic strategies for ameliorating age-related liver dysfunction and associated metabolic abnormalities.

Keywords

Aging; Familial hypercholesterolemia; Lipid metabolism; miR-23b-3p; sEV.

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