D-Glucosamine supplementation extends life span of nematodes and of ageing mice.
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.
1] Energy Metabolism Laboratory, ETH Zürich (Swiss Federal Institute of Technology Zurich), Zürich CH-8603, Switzerland [2] German Institute of Human Nutrition Potsdam-Rehbrücke, D-14558 Nuthetal, Germany [3].
Sandra
S
Weimer
1] Department of Human Nutrition, Institute of Nutrition, University of Jena, D-07743 Jena, Germany [2].
Josephine
J
Priebs
1] German Institute of Human Nutrition Potsdam-Rehbrücke, D-14558 Nuthetal, Germany [2] Department of Human Nutrition, Institute of Nutrition, University of Jena, D-07743 Jena, Germany.
Doreen
D
Kuhlow
Genome Analysis Group, Leibniz Institute for Age Research, Fritz-Lipmann-Institute, D-07745 Jena, Germany.
Marco
M
Groth
Systems Biology and Bioinformatics Group, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, D-07745 Jena, Germany.
Steffen
S
Priebe
1] Energy Metabolism Laboratory, ETH Zürich (Swiss Federal Institute of Technology Zurich), Zürich CH-8603, Switzerland [2] Department of Human Nutrition, Institute of Nutrition, University of Jena, D-07743 Jena, Germany [3] DFG Graduate School of Adaptive Stress Response #1715, D-07745 Jena, Germany.
Johannes
J
Mansfeld
Energy Metabolism Laboratory, ETH Zürich (Swiss Federal Institute of Technology Zurich), Zürich CH-8603, Switzerland.
Troy L
TL
Merry
Institute of Molecular Systems Biology, ETH Zürich (Swiss Federal Institute of Technology Zurich), Zürich CH-8093, Switzerland.
Sébastien
S
Dubuis
1] Energy Metabolism Laboratory, ETH Zürich (Swiss Federal Institute of Technology Zurich), Zürich CH-8603, Switzerland [2] Department of Human Nutrition, Institute of Nutrition, University of Jena, D-07743 Jena, Germany.
Beate
B
Laube
German Institute of Human Nutrition Potsdam-Rehbrücke, D-14558 Nuthetal, Germany.
Andreas F
AF
Pfeiffer
German Institute of Human Nutrition Potsdam-Rehbrücke, D-14558 Nuthetal, Germany.
Tim J
TJ
Schulz
Systems Biology and Bioinformatics Group, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, D-07745 Jena, Germany.
Reinhard
R
Guthke
Genome Analysis Group, Leibniz Institute for Age Research, Fritz-Lipmann-Institute, D-07745 Jena, Germany.
Matthias
M
Platzer
Institute of Molecular Systems Biology, ETH Zürich (Swiss Federal Institute of Technology Zurich), Zürich CH-8093, Switzerland.
Nicola
N
Zamboni
1] Energy Metabolism Laboratory, ETH Zürich (Swiss Federal Institute of Technology Zurich), Zürich CH-8603, Switzerland [2] Department of Human Nutrition, Institute of Nutrition, University of Jena, D-07743 Jena, Germany.
Kim
K
Zarse
1] Energy Metabolism Laboratory, ETH Zürich (Swiss Federal Institute of Technology Zurich), Zürich CH-8603, Switzerland [2] German Institute of Human Nutrition Potsdam-Rehbrücke, D-14558 Nuthetal, Germany [3] Department of Human Nutrition, Institute of Nutrition, University of Jena, D-07743 Jena, Germany.
Michael
M
Ristow
D000375:Aging / Q000187:drug effects*; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D005944:Glucosamine / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008136:Longevity / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D005944:Glucosamine