D-Glucosamine supplementation extends life span of nematodes and of ageing mice

作者：Weimer Sandra; Priebs Josephine; Kuhlow Doreen; Groth Marco; Priebe Steffen; Mansfeld Johannes; Merry Troy L; Dubuis Sebastien; Laube Beate; Pfeiffer Andreas F; Schulz Tim J; Guthke Reinhard; Platzer Matthias; Zamboni Nicola; Zarse Kim; Ristow Michael^*

来源：Nature Communications, 2014, 5(1): 3563.

DOI：10.1038/ncomms4563

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.

• 出版日期2014-4