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 +6 more
TLDR
Development of several mouse models in which hypothalamic stem/progenitor cells that co-express Sox2 and Bmi1 are ablated shows that ageing in mice started with a substantial loss of these hypothalamic cells, and ageing speed is substantially controlled by hypothalamicstem cells, partially through the release of exosomal miRNAs.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.read more
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Journal ArticleDOI
Exosome Theranostics: Biology and Translational Medicine.
TL;DR: The fundamental processes of exosome formation and uptake are described and the physiological and pathological roles of exOSomes in biology are illustrated with a focus on how exosomes can be exploited or engineered as powerful tools in translational medicine.
Journal ArticleDOI
Autophagy as a promoter of longevity: insights from model organisms
TL;DR: Recent studies in model organisms uncovered prominent links between autophagy and ageing, suggesting that by removing superfluous or damaged cellular content through lysosomal degradation, Autophagy supports tissue and organismal fitness and promotes longevity.
Journal ArticleDOI
The Aging Astrocyte Transcriptome from Multiple Regions of the Mouse Brain.
TL;DR: It is found that alterations to astrocytes in aging create an environment permissive to synapse elimination and neuronal damage, potentially contributing to aging-associated cognitive decline.
Journal ArticleDOI
Exosomes in cancer development, metastasis, and immunity.
Lin Zhang,Dihua Yu +1 more
TL;DR: The functions of exosomes in cancer development, metastasis, and anti-Tumor or pro-tumor immunity, plus their application in cancer treatment and diagnosis/prognosis are summarized.
Journal ArticleDOI
Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease
TL;DR: The findings that led to these conclusions are reviewed and how this sets the stage for new lines of investigation in which extracellular miRNAs are recognized as important mediators of intercellular communication and potential candidates for therapy of disease.
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