I've taken glucosamine-chondroitin for 12 years, the longest I've used any supplement.

Glucosamine is a natural compound found in cartilage. Being fairly active, I initially took it to protect my joints & promote cartilage health.

More recently, it has been found to be associated with reduced cancer mortality.

Moreover, it has also gained attention in longevity science due to its effects on metabolic pathways & cellular processes associated with aging.

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How Might Glucosamine Contribute to Longevity?

• AMPK Activation:
  • Glucosamine activates AMP-activated protein kinase (AMPK), an sensor in cells that regulates energy homeostasis.
  • AMPK activation shifts cellular metabolism from anabolic to catabolic processes, favoring energy-producing over energy-consuming pathways.
• Reduction of Inflammation:
  • Glucosamine inhibits the NF-κB signaling pathway, a key regulator of the inflammatory response in cells.
  • By reducing the production of pro-inflammatory cytokines like TNF-α and IL-6, glucosamine decreases systemic inflammation, potentially alleviating age-related inflammatory conditions.

• Autophagy Induction:
  • Glucosamine induces autophagy through the mammalian target of rapamycin (mTOR) pathway, a central regulator of cell growth and metabolism.
  • This autophagy induction clears damaged organelles, like mitochondria, and misfolded proteins, enhancing cellular homeostasis.
• Mitochondrial Function & Oxidative Stress Reduction:
  • Glucosamine can preserve mitochondrial integrity by suppressing mitochondrial reactive oxygen species generation.
  • Mitochondrial biogenesis is found to be enhanced.

• Interaction with Longevity Genes:
  • Glucosamine may influence genes related to the sirtuin family, particularly SIRT1, which plays a role in cellular stress resistance and longevity.
  • It might also interact with FOXO genes, which are involved in stress resistance, metabolism, and cell death, key areas in aging research.

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The study of glucosamine in the context of aging may reveal new targets for healthy-aging interventions & help clarify the mechanisms underlying dietary influences on aging.

In subsequent episodes, we’ll explore various natural foods that are rich in or contribute to the body’s glucosamine supply, examining both food and supplement sources to understand how diet can support joint health & potentially influence longevity.

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Disclaimer

This information is not medical advice nor is it lifestyle advice. This content and other content on this website is for informational and educational purposes only and is not intended to be a substitute for lifestyle advice, medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical or health condition.

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References

• Tesoriere, G., Vento, R., & Calvaruso, G. (1975). Inhibitory effect of D-glucosamine on glycolysis in bovine retina. Biochimica et Biophysica Acta (BBA) - General Subjects, 385(1), 58-67.
• Dalirfardouei, R., Karimi, G., & Jamialahmadi, K. (2016). Molecular mechanisms and biomedical applications of glucosamine as a potential multifunctional therapeutic agent. Life Sciences, 152, 21-29.
• Weimer, S., et al. (2014). D-Glucosamine supplementation extends life span of nematodes and of ageing mice. Nature Communications, 5, 3563.
• Yang, W., & Hekimi, S. (2010). A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biology, 8(12), e1000556.
• Hwang, A. B., et al. (2014). Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans. Proceedings of the National Academy of Sciences, 111(E4458-E4467).
• Banerjee, P. S., Lagerlof, O., & Hart, G. W. (2016). Roles of O-GlcNAc in chronic diseases of aging. Molecular Aspects of Medicine, 51, 1-15.
• Bell, G. A., Kantor, E. D., Lampe, J. W., Shen, D. D., & White, E. (2012). Use of glucosamine and chondroitin in relation to mortality. European Journal of Epidemiology, 27(8), 593-603.
• Han, C., Gu, Y., Shan, H., et al. (2017). O-GlcNAcylation of SIRT1 enhances its deacetylase activity and promotes cytoprotection under stress. Nature Communications, 8, 1491.
• Weimer, S., Priebs, J., Kuhlow, D., Groth, M., Priebe, S., Mansfeld, J., et al. (2014). D-Glucosamine supplementation extends life span of nematodes and of ageing mice. Nature Communications, 5(1), 3563.
• Li, Z. H., Gao, X., Chung, V. C., Zhong, W. F., Fu, Q., Lv, Y. B., et al. (2020). Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study. Annals of the Rheumatic Diseases, 79(6), 829-836.
• Yu, Z., Ju, Y., & Liu, H. (2017). Anti-lung cancer effect of glucosamine by suppressing the phosphorylation of FOXO. Molecular Medicine Reports, 16(3), 3395-3400.
• Dalirfardouei, R., Karimi, G., & Jamialahmadi, K. (2016). Molecular mechanisms and biomedical applications of glucosamine as a potential multifunctional therapeutic agent. Life Sciences, 152, 21-29.
• Zhou, J., Wu, Z., Lin, Z., Wang, W., Wan, R., & Liu, T. (2022). Association between glucosamine use and cancer mortality: A large prospective cohort study. Frontiers in Nutrition, 9.
• Chiu, H. W., Li, L. H., Hsieh, C. Y., et al. (2019). Glucosamine inhibits IL-1β expression by preserving mitochondrial integrity and disrupting assembly of the NLRP3 inflammasome. Scientific Reports, 9, 5603.
• Kim, M. E., Kim, D. H., & Lee, J. S. (2022). FoxO Transcription Factors: Applicability as a Novel Immune Cell Regulators and Therapeutic Targets in Oxidative Stress-Related Diseases. International Journal of Molecular Sciences, 23(19), 11877.

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