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DMH neurons regulate aging and lifespan in mice through hypothalamic-adipose inter-tissue communication. | LitMetric

DMH neurons regulate aging and lifespan in mice through hypothalamic-adipose inter-tissue communication.

Cell Metab

Departments of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:

Published: February 2024

AI Article Synopsis

Article Abstract

Recent studies have shown that the hypothalamus functions as a control center of aging in mammals that counteracts age-associated physiological decline through inter-tissue communications. We have identified a key neuronal subpopulation in the dorsomedial hypothalamus (DMH), marked by Ppp1r17 expression (DMH neurons), that regulates aging and longevity in mice. DMH neurons regulate physical activity and WAT function, including the secretion of extracellular nicotinamide phosphoribosyltransferase (eNAMPT), through sympathetic nervous stimulation. Within DMH neurons, the phosphorylation and subsequent nuclear-cytoplasmic translocation of Ppp1r17, regulated by cGMP-dependent protein kinase G (PKG; Prkg1), affect gene expression regulating synaptic function, causing synaptic transmission dysfunction and impaired WAT function. Both DMH-specific Prkg1 knockdown, which suppresses age-associated Ppp1r17 translocation, and the chemogenetic activation of DMH neurons significantly ameliorate age-associated dysfunction in WAT, increase physical activity, and extend lifespan. Thus, these findings clearly demonstrate the importance of the inter-tissue communication between the hypothalamus and WAT in mammalian aging and longevity control.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10922643PMC
http://dx.doi.org/10.1016/j.cmet.2023.12.011DOI Listing

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