Hypothalamic stem cells control ageing speed partly through exosomal miRNAs

Yalin Zhang, Min Soo Kim, Baosen Jia, Jingqi Yan, Juan Pablo Zuniga-Hertz, Cheng Han, Dongsheng Cai

Research output: Contribution to journalArticle

154 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)52-57
Number of pages6
JournalNature
Volume548
Issue number7665
DOIs
StatePublished - Aug 3 2017

ASJC Scopus subject areas

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    Zhang, Y., Kim, M. S., Jia, B., Yan, J., Zuniga-Hertz, J. P., Han, C., & Cai, D. (2017). Hypothalamic stem cells control ageing speed partly through exosomal miRNAs. Nature, 548(7665), 52-57. https://doi.org/10.1038/nature23282