Glucosamine May Be a Caloric Restriction Mimetic

Glucosamine emulates caloric restriction in rats due to mitohormesis. 


Glucosamine is a polysaccharide that naturally occurs in cartilaginous joint tissues and is involved in protein and lipid synthesis. Glucosamine is also present in other tissues, such as skin, nails, bones, and ligaments. Synovial fluid contains glucosamine and occupies the space between joints, helping to reduce the friction of joint surfaces. Glucosamine is commonly taken as a supplement to help with the joint pain and inflammation associated with aging.

What does not kill us makes us stronger

The study we want to spotlight today shows how glucosamine produces a caloric restriction-like effect in rats. The researchers treated young rats and accelerated aging rats with regular doses of glucosamine, then they examined a number of aging biomarkers.

There was a significant rise in reactive oxygen species (ROS) in both young and accelerated aging rats. ROS are reactive molecules and free radicals derived from oxygen, and while they do have some beneficial uses, such as being used by immune cells as a component of the killing response to combat microbial invasion, they are also very harmful to cells. Free radicals each possess an unpaired electron, making them highly reactive and thus able to damage all macromolecules, including lipids, proteins and nucleic acids.

ROS is produced as a byproduct during the mitochondrial electron transport of aerobic respiration or by oxidoreductase enzymes and metal catalyzed oxidation. Mitochondria also produce increasing amounts of potentially harmful ROS as they become increasingly dysfunctional, and mitochondrial dysfunction is a hallmark of aging.


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It was originally thought that only phagocytic cells, which protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells, such as macrophages and neutrophils, produced ROS. This was shown to be incorrect, and more recent research shows that ROS has a role in cellular signaling, serving as both an intra- and intercellular messenger and influencing gene expression, apoptosis, and the activation of cellular signaling cascades.

The researchers suggest that glucosamine spurs a transient increase in ROS, which, in turn, triggers a protective mitohormetic response. Mitohormesis describes a process in which low levels of mitochondrial ROS act as signaling molecules to trigger a cascade of cellular events that protect the cells from harmful effects. Essentially, the small amount of stress caused by the ROS encourages the cell to raise its shields.

They believe that this response produces an effect similar to the stress response observed in caloric restriction, and multiple biomarkers showed that this is the case. The old saying “What does not kill us makes us stronger” appears to apply here.

Aging is strongly correlated with several non-communicable disorders such as diabetes, obesity, cardiovascular disease, and neurodegenerative conditions. Glucosamine (2-amino-2-deoxy-D-glucose, GlcN) is a naturally occurring amino sugar and is reported to act as a caloric restriction mimetic (CRM). In young and D-galactose-induced accelerated rat aging models, we tested a persistent oral dietary dose of GlcN and evaluated various aging biomarkers in erythrocytes and plasma. A significant increase in the reactive oxygen species (ROS) was observed in GlcN treated young and accelerated senescent rat model. Increased value of Ferric Reducing Antioxidant Potential (FRAP), Superoxide Dismutase (SOD), Catalase (CAT), and Plasma membrane reduced system (PMRS) was observed. We suggest that GlcN induces a mitohormetic impact by a transient increase in ROS. Our findings indicate that GlcN may be a successful CRM.


It should be noted that these results are in rats, but the idea that similar effects may occur in humans taking glucosamine is not beyond the realm of possibility. Caloric restriction increases lifespan in multiple species, so finding a way to emulate this effect without the need to engage in caloric restriction could have the potential to help people with metabolic conditions, such as diabetes and obesity.


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It appears to be the case that glucosamine significantly reduces all-cause mortality in humans, according to not one but two large-scale studies conducted last year. Glucosamine is cheap, readily available, and has compelling health and safety data behind it, and it would be a dietary supplement worth considering for a science-based personal longevity strategy.

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About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.