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Hypothalamic stem cells control ageing speed partly through exosomal miRNAs

Author

Listed:
  • Yalin Zhang

    (Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine)

  • Min Soo Kim

    (Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine)

  • Baosen Jia

    (Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine)

  • Jingqi Yan

    (Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine)

  • Juan Pablo Zuniga-Hertz

    (Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine)

  • Cheng Han

    (Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine)

  • Dongsheng Cai

    (Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine)

Abstract

It has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Here we develop several mouse models in which hypothalamic stem/progenitor cells that co-express Sox2 and Bmi1 are ablated, as we observed that ageing in mice started with a substantial loss of these hypothalamic cells. Each mouse model consistently displayed acceleration of ageing-like physiological changes or a shortened lifespan. Conversely, ageing retardation and lifespan extension were achieved in mid-aged mice that were locally implanted with healthy hypothalamic stem/progenitor cells that had been genetically engineered to survive in the ageing-related hypothalamic inflammatory microenvironment. Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing. In conclusion, ageing speed is substantially controlled by hypothalamic stem cells, partially through the release of exosomal miRNAs.

Suggested Citation

  • Yalin Zhang & Min Soo Kim & Baosen Jia & Jingqi Yan & Juan Pablo Zuniga-Hertz & Cheng Han & Dongsheng Cai, 2017. "Hypothalamic stem cells control ageing speed partly through exosomal miRNAs," Nature, Nature, vol. 548(7665), pages 52-57, August.
    • Handle: RePEc:nat:nature:v:548:y:2017:i:7665:d:10.1038_nature23282
    DOI: 10.1038/nature23282
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    Cited by:

    1. Zhen-Xing Wang & Zhong-Wei Luo & Fu-Xing-Zi Li & Jia Cao & Shan-Shan Rao & Yi-Wei Liu & Yi-Yi Wang & Guo-Qiang Zhu & Jiang-Shan Gong & Jing-Tao Zou & Qiang Wang & Yi-Juan Tan & Yan Zhang & Yin Hu & Yo, 2022. "Aged bone matrix-derived extracellular vesicles as a messenger for calcification paradox," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    2. Nicola Alessio & Anna Lisa Brigida & Gianfranco Peluso & Nicola Antonucci & Umberto Galderisi & Dario Siniscalco, 2020. "Stem Cell-Derived Exosomes in Autism Spectrum Disorder," IJERPH, MDPI, vol. 17(3), pages 1-10, February.

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