Hypothalamic stem cells control ageing speed partly through exosomal miRNAs

Article

关键词: EXTENDS LIFE-SPAN;    BETA/NF-KAPPA-B;    SUBVENTRICULAR ZONE;    MICRORNA REGULATION;    ADULT HIPPOCAMPUS;    IKK-BETA;    NEUROGENESIS;    MICE;    OBESITY;    DIFFERENTIATION;   

DOI  :  10.1038/nature23282

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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