Content courtesy of ergo-log.com
It’s been on the market for about twenty years: glucosamine – an amino acid with sugar attached that, according to small studies, protects joints (and according to larger studies, mainly sponsored by the pharmaceutical sector, has no effect at all). This same glucosamine extends lives according to Swiss and German molecular biologists by imitating the effect of a low-carbohydrate diet.
Yes, this is a study that we take seriously. To start with, it wasn’t sponsored by a supplements manufacturer, but by the German government.
Secondly, it was published in Nature Communications, a scientific journal with an impact factor of just over 10. Nature Communications is in the top two percent of most influential scientific journals there are.
And, last but not least, this study was done by a team led by Michael Ristow, a big name in research on anti-aging, antioxidants and carbohydrate metabolism.
The glucosamine found in supplements mainly comes from crab shells, but the body also produces its own glucosamine which is found mainly in the joints. It was already known that high doses of glucosamine inhibit the conversion of glucose into energy – and this property piqued the curiosity of the researchers.
They had already previously shown that compounds that inhibit carbohydrate metabolism, and also low-carb diets, can extend the lifespan of laboratory animals.
Add to that the fact that some epidemiologists believe that glucosamine reduces the chance of developing some forms of cancer and extends life expectancy, then you understand why the researchers gave glucosamine to microscopic worms, Caenorhabditis elegans [one shown below] and mice in their laboratory. The researchers wanted to see whether the lab animals would live longer as a result of supplementation.
And the worms and mice did indeed do this. The red line in the graph below is the survival curve of the worms that had been given glucosamine; the black line is the survival curve o the worms in the control group.
In the bar charts red also represents the animals that had been given glucosamine.
Glucosamine worked exactly as you’d expect. It inhibited glucose burning and the formation of ATP [structural formula on the right] energy molecules by cells.
As a result of the disruption to the animals’ metabolism, their mitochondria started to make more free radicals [such as hydrogen peroxide H2O2] after two days. The cells reacted to this by stepping up their production of endogenous antioxidants, such as the enzymes superoxide dismutase [SOD] and catalase. As a result of this the concentration of free radicals in the cell went down – and reduced the tempo of aging.
When the researchers gave mice glucosamine, they lived to be older than the mice that had not been given glucosamine.
The researchers mixed glucosamine into the animals’ food from the age of 100 days. The human equivalent dose that they used is about 1g per 10 kg bodyweight per day. The type of glucosamine the researchers used is not revealed in the article.
The mice also produced less ATP when they were given glucosamine.
If the mice were given antioxidants such as N-acetylcysteine (NAC] or butylated hydroxyl anisole [BHA] the life-extending effect of glucosamine disappeared.
The mice that were given glucosamine started to burn more proteins. Glucosamine caused the cells to manufacture more receptors to absorb the amino acids. In mice where the receptors didn’t work, glucosamine had no life extending effect. So it would seem there is a relationship between life extension through glucosamine and protein metabolism.
“These findings implicate that glucosamine supplementation may be a versatile approach to delay ageing in humans”, the researchers write.
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.
PMID: 24714520 [PubMed – in process] PMCID: PMC3988823
Content courtesy of ergo-log.com