ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2018) 15 1.3 | DOI: 10.1530/ey.15.1.3

ESPEYB15 1 Pituitary and Neuroendocrinology New mechanisms (6 abstracts)

1.3 Hypothalamic stem cells control ageing speed partly through exosomal miRNAs

Zhang Y , Kim MS , Jia B , Yan J , Zuniga-Hertz JP , Han C & Cai D


Department of Molecular Pharmacology, Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine, New York, USA


To read the full abstract: Nature 2017;548:52-57

The central nervous system contributes to ageing. The hypothalamus seems to be particularly important in this process. Recent studies have demonstrated a link between ageing and a decrease of neurogenesis in the hippocampus and the subventricular zone of the lateral ventricle in the brain. Neural stem/progenitor cells (NSC) reside in those regions in the brain and are involved in the neurogenesis. A link between the presence of NSC, neurogenesis and ageing has thus been hypothesised. Recently, this group described the role of the hypothalamus in systemic ageing, and the unexpected function of GnRH to decelerate ageing1.

Here, Zhang et al. extend the concept to adult NSC, which have been described in the hypothalamus (htNSC). With very elegant experiments, they show that loss of htNSC accelerates ageing, whereas implantation of htNSC resistant to neuroinflammation has an anti-ageing and longevity effect. In addition, they report an endocrine function of these cells, which secrete exosomal miRNAs. The inhibition of exosomal miRNAs secretion blocks the effect of htNSC on ageing. More surprisingly, treatment of mid-aged mice with exosomes reduces the effect of the ablation of NSC and could be related to GnRH. In addition, to describe a new mechanism, Zhang et al. propose a very innovative treatment based on the administration of purified exosomes.

1. Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y, Li B, Liu G, Cai D Hypothalamic programming of systemic ageing involving IKK-beta, NF-kappaB and GnRH. Nature. 2013;497(7448):211-216

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