Important new paper by the group of Michael Ristow, appearing in Nature Communications: 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.
Further, from the body of the paper:
We here find that GlcN inhibits glycolysis to cause an energy deficit that induces mitochondrial biogenesis and alternate fuel use, namely amino-acid oxidation. This is paralleled by an extension of life span in both C. elegans and ageing mice, the latter also showing improved glucose metabolism. These findings implicate that GlcN supplementation may be a versatile approach to delay ageing in humans.
Glucosamine impairs glycolysis, a proven way to extend lifespan. This also extends the concept elaborated by Ristow, mitohormesis.
A quick note about extending findings from basic research to practical use, since one might think that life extension in C elegans (a worm) wouldn’t have much to do with humans. Cynthia Kenyon is a well-known researcher on aging who also uses C elegans in her research. When she discovered that adding glucose to the media on which her worms grew caused the worms to die younger, she herself immediately switched to a low-carb diet.