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


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.

1. Introduction
Age-related diseases are becoming a social problem worldwide. Among them, the concept of “locomotive syndrome” has been proposed and attracted attention due to its association with a decrease in quality
of life (QOL) [1]. Locomotive syndrome is a condition in which a person has difficulty walking due to impairment or deterioration of the motor organs. Consequently, there is an increased risk for a person to require nursing care. The causes of locomotive syndrome can be broadly divided into two categories: diseases of the musculoskeletal system and age-related musculoskeletal dysfunction. Diseases of the musculoskeletal system are associated with a variety of age-related musculoskeletal diseases, such as osteoarthritis (OA) and osteoporosis. In contrast, age-related musculoskeletal dysfunction includes muscle loss and muscle weakness [2,3]. Typical indicators of locomotive syndrome include loss of muscle strength and a decrease in walking speed. Walking speeddecreases with age [4] and has been positively correlated with survival rates, which could be an indicator of vitality [5]. Thus, reducing locomotive syndrome may maintain QOL. OA is a musculoskeletal disease that causes locomotive syndrome. Among OA and related diseases, knee OA (KOA) is the most common type and is associated with increased pain and difficulty in walking and a significant deterioration in QOL. Although current treatment options for KOA include surgical, pharmacological, and physical therapies, their effects are limited. Currently, treatment for KOA is dominated by pharmacotherapy to relive pain, including non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors. However, NSAIDs carry a risk of causing gastrointestinal disorders, and COX-2 inhibitors can cause adverse cardiovascular effects. There are significant concerns regarding the side effects of these treatments [6]. Glucosamine (2-amino-2-deoxy-D-glucose) is a…