Inflammation, Stem Cells, and the Aging Hypothalamus.

The aging hypothalamus has been hypothesized to play a key role in vertebrate aging. Increased inflammation in microglial cells during aging reduces the number of neural stem cells (NSCs) in the mediobasal region of the hypothalamus. Ectopic brain-specific expression of SIRT1 and localized hypothalamic expression of a dominantly acting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor to microglia or to NSCs extend life span in mice. NSCs in the hypothalamus secrete miRNA-containing exosomes and gonadotropin-releasing hormone (GnRH) that oppose aging-associated neurological and skeletomuscular dysfunction. These results suggest that stem cells are not mere repositories of future differentiated cells, but can also be active physiological effectors. Development of drugs that attenuate microglial inflammation and/or promoted maintenance of NSC viability may have significant utility for extending health and life span.