April 09, 2014

 The widely used food supplement glucosamine promotes longevity in ageing mice by approximately 10% due to improved glucose metabolism. Michael Ristow, a professor at ETH Zurich, and his team find that the compound does so “by mimicking a low-carb diet in elderly mice reflecting human retirees”.

Glucosamine has been freely available in drugstores for many decades. It is widely used to treat arthritis and to prevent joint degeneration. Moreover, glucosamine is known to delay cancer growth. In addition, glucosamine reduces metabolism of nutritive sugars, as was already shown some 50 years ago.

Fightaging – If you dig into the paper, you’ll find that life extension in mice is modest, around 10%” – ignores that the glucosamine diet was started late in life (the mouse age equivalent of 65 years), and for the best responders (see graphs in Figure 3) extends lifespan much more than 10%. The authors of the paper thought the results were good enough to start the regimen themselves.

GlcN promotes hepatic energy depletion and increases life span in ageing mice.

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

Fightaging has the following perspective on this research

While destined to be a deserted sideline of longevity science at some point in the years ahead, research into calorie restriction mimetic drugs is presently in its heyday. Calorie restriction with optimal nutrition slows aging and extends life in near every species tested to date, though the shorter the natural life span of the species the greater the effect. A calorie restricted mouse can live 40% longer in excellent health, but that certainly isn’t the case for humans – we’d have noticed an effect that large long ago. This is interesting, because the short-term effects on metabolism and markers of health are similarly large and beneficial in both species. Nonetheless, the consensus in the research community expects the effects of calorie restriction on human life span to be at the most in the ballpark of a 5% increase. The effects on health are much more impressive, however: if calorie restriction were a drug, it would dwarf the sales of any other pharmaceutical created to date, and deservedly so.

So if this is so great, why is it going to be a backwater? Because the objective of a calorie restriction mimetic drug is, as the name suggests, to mimic the metabolic response to calorie restriction – to produce at least some of the same health benefits. A perfect mimetic would result in the same outcome as practicing calorie restriction. But that means a mere boost to health and life that is large in comparison to doing nothing, but is tiny on the scale of what is possible through future medical science. We are entering the era of rejuvenation biotechnology, in which researchers are even today working on the foundations of ways to reverse the cellular and molecular damage that causes degenerative aging. That is the road to indefinite health, completely prevention of age-related disease, and a youth that lasts for as long as you want it to. It won’t take much of that for the current fad of drug development aimed at slightly slowing down aging to wither away in favor of the obviously better line of business.

Extended lifespan by almost 10%

In the recently published study that was performed at ETH Zurich and four German re-search institutions, Ristow and his colleagues applied glucosamine to roundworms and found that they live around 5% longer than their untreated counterparts.

Next and most importantly, the researchers fed glucosamine to ageing mice in addition to their normal diet. The mice were 100 weeks of age, reflecting a comparative human age of approximately 65 years. A control group of mice received no glucosamine while otherwise receiving an identical diet. Feeding the supplement to mice extended their lifespan by almost 10%, reflecting around 8 additional years of human lifespan. Moreo-ver, glucosamine improved glucose metabolism in elderly mice indicating protection from diabetes, a life-threatening disease most prevalent amongst the elderly.
Mimicking a low-carb diet

Additional analyses revealed that glucosamine feeding promotes the breakdown of amino acids in both worms and mice. Amino acids are key components of proteins, and they become preferentially metabolized in the absence of carbohydrates. As Ristow points out, “this reflects the metabolic state of a low-carb diet due to glucosamine supplementation alone – while these mice ingested the same amount of carbohydrates as their unsupplemented counterparts.” This implies that glucosamine would mimic a low-carb diet in humans as well – without the necessity of reducing the uptake of carbohydrates in our daily diet.

Should we now start taking glucosamine supplements? Ristow replies: “This may be considered a valid option, and yes, I have started taking glucosamine myself.” Howev-er, he points out that “diabetics should perform tight blood glucose control, especially during the first weeks.” Interestingly, two recent epidemiological studies on more than 77,000 individuals suggest that intake of glucosamine supplements is associated with reduced mortality in humans [references 3, 4]. “Unlike with our longer living mice, such an association is no definite proof of the effectiveness of glucosamine in humans”, says Ristow. He continues, “But the chances are good, and since unlike with most other potentially lifespan-extending drugs there are no known relevant side effects of glucosamine supplementation, I would tend to recommend this supplement.”