Shifting the focus of d-glucosamine from a dietary supplement for knee osteoarthritis to a potential anti-aging drug

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d -Glucosamine is a protective dietary supplement or medicine for osteoarthritis of the knee, a musculoskeletal disease that leads to a significant deterioration in daily activities and quality of life. As glucosamine can restore damaged cartilage worn down by joint disease, there was hope it could also improve symptoms. Data from several clinical studies on the efficacy of glucosamine on knee joint function conducted since the 1980s have been used in certain meta-analyses and epidemiological studies since 2010, yet the effect of glucosamine on the knee joints remains controversial. Concurrently, many drugs have been investigated for their anti-aging properties. Among these drugs, glucosamine has recently been discovered to be a potential substance with convincing evidence for increasing human lifespan. More interestingly, Zhi-Hao et al. have recently reported that the use of glucosamine was associated with a reduction in total mortality regardless of its effect on the knee (Annals of the Rheumatic Diseases 79(2020)829–836). Additionally, glucosamine prolongs the lifespan of the nematode Caenorhabditis elegans , possibly due to its calorie restriction-mimicking effect by improving energy metabolism and inducing autophagy. Thus, the recent large-scale epidemiological report on glucosamine intake and mortality, as well as our animal studies (Journal of Applied Glycoscience 65(2018)37–43), has become relevant. However, the potential significance of metabolism of glucosamine in anti-aging should be more clearly investigated in the future. This paper presents the novel concept of repositioning glucosamine from a dietary supplement or an OTC drug for osteoarthritis improvements to an anti-aging drug for healthy lifespan extension. • Glucosamine has been conventionally proposed as a protective dietary supplement or medicine for osteoarthritis of the knee. • A recent meta-analysis has reported a small positive effect for glucosamine on osteoarthritis. • There are new epidemiological reports on the effects of glucosamine regarding low mortality. • The mechanism underlying the effects of these drugs is expected to involve a calorie restriction-mimicking effect by improving energy metabolism and inducing autophagy. • The drug repositioning of glucosamine as from osteoarthritis to antiaging dietary supplement could have been expected.