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Nature aging
Jun, 2024;4 (6): 814-838.

Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism.

Xiaorui Chen, Yang Luo, Qing Zhu, Jingzi Zhang, Huan Huang, Yansheng Kan, Dian Li, Ming Xu, Shuohan Liu, Jianxiao Li, Jinmeng Pan, Li Zhang, Yan Guo, Binghao Wang, Guantong Qi, Zhen Zhou, Chen-Yu Zhang, Lei Fang, Yanbo Wang, Xi Chen
Author Information
  1. Xiaorui Chen: Center for Reproductive Medicine and Department of Andrology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China.
  2. Yang Luo: Center for Reproductive Medicine and Department of Andrology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China.
  3. Qing Zhu: Center for Reproductive Medicine and Department of Andrology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China.
  4. Jingzi Zhang: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China. ORCID
  5. Huan Huang: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  6. Yansheng Kan: Center for Reproductive Medicine and Department of Andrology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China.
  7. Dian Li: Center for Reproductive Medicine and Department of Andrology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China.
  8. Ming Xu: Center for Reproductive Medicine and Department of Andrology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China.
  9. Shuohan Liu: Center for Reproductive Medicine and Department of Andrology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China.
  10. Jianxiao Li: Institute of Systems, Molecular and Integrative Biology, School of Life Sciences, University of Liverpool, Liverpool, UK.
  11. Jinmeng Pan: Center for Reproductive Medicine and Department of Andrology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China.
  12. Li Zhang: Center for Reproductive Medicine and Department of Andrology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China.
  13. Yan Guo: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China.
  14. Binghao Wang: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China.
  15. Guantong Qi: Center for Reproductive Medicine and Department of Andrology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China.
  16. Zhen Zhou: Center for Reproductive Medicine and Department of Andrology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China.
  17. Chen-Yu Zhang: Center for Reproductive Medicine and Department of Andrology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China. cyzhang@nju.edu.cn. ORCID
  18. Lei Fang: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China. njfanglei@nju.edu.cn. ORCID
  19. Yanbo Wang: Center for Reproductive Medicine and Department of Andrology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China. ybwang@nju.edu.cn. ORCID
  20. Xi Chen: Center for Reproductive Medicine and Department of Andrology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, China. xichen@nju.edu.cn. ORCID
PMID: 38627524 DOI: 10.1038/s43587-024-00612-4

Abstract

Recent investigations into heterochronic parabiosis have unveiled robust rejuvenating effects of young blood on aged tissues. However, the specific rejuvenating mechanisms remain incompletely elucidated. Here we demonstrate that small extracellular vesicles (sEVs) from the plasma of young mice counteract pre-existing aging at molecular, mitochondrial, cellular and physiological levels. Intravenous injection of young sEVs into aged mice extends their lifespan, mitigates senescent phenotypes and ameliorates age-associated functional declines in multiple tissues. Quantitative proteomic analyses identified substantial alterations in the proteomes of aged tissues after young sEV treatment, and these changes are closely associated with metabolic processes. Mechanistic investigations reveal that young sEVs stimulate PGC-1α expression in vitro and in vivo through their miRNA cargoes, thereby improving mitochondrial functions and mitigating mitochondrial deficits in aged tissues. Overall, this study demonstrates that young sEVs reverse degenerative changes and age-related dysfunction, at least in part, by stimulating PGC-1α expression and enhancing mitochondrial energy metabolism.

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Grants

  1. No. 32022015 and 31871295/National Natural Science Foundation of China (National Science Foundation of China)

MeSH Term

Animals
Extracellular Vesicles
Energy Metabolism
Mitochondria
Mice
Aging
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Proteomics
Mice, Inbred C57BL
MicroRNAs
Male

Chemicals

Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Ppargc1a protein, mouse
MicroRNAs
Journal Article

Links to CNCB-NGDC Resources

GSA: CRA013558 (Changes of plasma miRNA with age)
Article has an altmetric score of 244

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