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 and Dongsheng Cai ()
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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

Nature, 2017, vol. 548, issue 7665, 52-57

Abstract: 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.

Date: 2017
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DOI: 10.1038/nature23282

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