Pluto Bioinformatics

GSE54853: RNA-seq of C.elegans and M.musculus in the presence and absence of D-Glucosamine (GlcN)

Bulk RNA sequencing

D-Glucosamine (2-amino-2-deoxy-D-glucose, C.A.S.# 3416-24-8) (GlcN) is a freely available and commonly used dietary supplement possibly promoting cartilage health in humans which also acts as an inhibitor of glycolysis.; We here find that GlcN extends C. elegans lifespan by impairing glucose metabolism to activate AMP-activated protein kinase (AMPK/AAK2) leading to increased mitochondrial biogenesis.; Consistent with the concept of mitohormesis, this promotes increased formation of mitochondrial reactive oxygen species (ROS) and p38/PMK-1-mediated stress signaling culminating in increased expression of the nematodal amino acid-transporter 1 (aat-1) gene.; Ameliorating mitochondrial ROS formation as well as impairment of aat-1-expression abolishes GlcN-mediated lifespan extension in a NRF2/SKN-1-dependent fashion.; Notably and unlike other calorie restriction mimetics (CRM) like 2-deoxy-D-glucose (2DG, DOG), GlcN extends lifespan of aging C57BL/6 mice (log-rank: p=0.002; cox regression: p=0.01) similarly paralleled by an induction of mitochondrial biogenesis, increased expression of several murine amino acid transporters, as well as increased amino-acid catabolism.; Taken together, GlcN mimics a ketogenic diet to extend healthspan in evolutionary distinct species. SOURCE: Steffen Priebe (steffen.priebe@hki-jena.de) - Hans-Knöll-Institute (HKI)