caa a22 4500 528785753 20190713030955.0 cr unu---uuuuu 180924s2014 xx s 000 0 eng 10.3929/ethz-b-000083876 doi 10.1038/ncomms4563 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/83876 D-Glucosamine supplementation extends life span of nematodes and of ageing mice: 10.1038/ncomms4563 [Elektronische Daten] [Sandra Weimer, Josephine Priebs, Doreen Kuhlow, Marco Groth, Steffen Priebe, Johannes Mansfeld, Troy L. Merry, Sébastien Dubuis, Beate Laube, Andreas F. Pfeiffer, Tim J. Schulz, Reinhard Guthke, Matthias Platzer, Nicola; id_orcid 0000-0003-1271-1021 Zamboni, Kim Zarse, Michael; id_orcid 0000-0003-2109-2453 Ristow] Nat Commun Open access ethresearch D-Glucosamine (GlcN) is a freely available and commonly used dietary supplement potentially promoting cartilage health in humans, which also acts as an inhibitor of glycolysis. Here we show that GlcN, independent of the hexosamine pathway, extends Caenorhabditis elegans life span by impairing glucose metabolism that activates AMP-activated protein kinase (AMPK/AAK-2) and increases mitochondrial biogenesis. Consistent with the concept of mitohormesis, GlcN promotes increased formation of mitochondrial reactive oxygen species (ROS) culminating in increased expression of the nematodal amino acid-transporter 1 (aat-1) gene. Ameliorating mitochondrial ROS formation or impairment of aat-1-expression abolishes GlcN-mediated life span extension in an NRF2/SKN-1-dependent fashion. Unlike other calorie restriction mimetics, such as 2-deoxyglucose, GlcN extends life span of ageing C57BL/6 mice, which show an induction of mitochondrial biogenesis, lowered blood glucose levels, enhanced expression of several murine amino-acid transporters, as well as increased amino-acid catabolism. Taken together, we provide evidence that GlcN extends life span in evolutionary distinct species by mimicking a low-carbohydrate diet. Creative Commons Attribution 3.0 Unported http://creativecommons.org/licenses/by/3.0 ethresearch Weimer Sandra joint author Priebs Josephine joint author Kuhlow Doreen joint author Groth Marco joint author Priebe Steffen joint author Mansfeld Johannes joint author Merry Troy L. joint author Dubuis Sébastien joint author Laube Beate joint author Pfeiffer Andreas F. joint author Schulz Tim J. joint author Guthke Reinhard joint author Platzer Matthias joint author Zamboni Nicola; id_orcid 0000-0003-1271-1021 joint author Zarse Kim joint author Ristow Michael; id_orcid 0000-0003-2109-2453 joint author Nature Communications London : Nature Publishing Group 5, p. 3563 2041-1723 http://hdl.handle.net/20.500.11850/83876 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/83876 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Weimer Sandra joint author ETHRESEARCH 700 1- Priebs Josephine joint author ETHRESEARCH 700 1- Kuhlow Doreen joint author ETHRESEARCH 700 1- Groth Marco joint author ETHRESEARCH 700 1- Priebe Steffen joint author ETHRESEARCH 700 1- Mansfeld Johannes joint author ETHRESEARCH 700 1- Merry Troy L. joint author ETHRESEARCH 700 1- Dubuis Sébastien joint author ETHRESEARCH 700 1- Laube Beate joint author ETHRESEARCH 700 1- Pfeiffer Andreas F. joint author ETHRESEARCH 700 1- Schulz Tim J. joint author ETHRESEARCH 700 1- Guthke Reinhard joint author ETHRESEARCH 700 1- Platzer Matthias joint author ETHRESEARCH 700 1- Zamboni Nicola; id_orcid 0000-0003-1271-1021 joint author ETHRESEARCH 700 1- Zarse Kim joint author ETHRESEARCH 700 1- Ristow Michael; id_orcid 0000-0003-2109-2453 joint author ETHRESEARCH 773 0- Nature Communications London : Nature Publishing Group 5, p. 3563 2041-1723 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access