High sugar consumption, leading to hyperglycemia, and accelerated aging, have a lot more in common than most people think. It’s no surprise that the sugar industry goes to great lengths to hide the amount of added sugar in everyday foods, evidenced by the lack of a daily value percentage on nutrition labels. But what most people probably aren’t aware of is that hyperglycemia (i.e. high blood sugar), creates products in our bodies that accumulate over time and are associated with pre-mature aging and many age-associated diseases. These products are appropriately (or ironically) called AGE’s, and they are Advanced Glycation End products. AGE’s are irreversibly created when proteins and other macromolecules come into contact with sugar molecules in a non-enzymatic, and concentration dependent manner (Zeng et al., 2019). This attachment of sugar molecules with other molecules in our body is termed glycation, and it’s gained growing interest in the field of age-associated diseases.
AGE’s are molecules throughout the body that are the result of sugar molecules non-enzymatically attaching themselves to macromolecules such proteins, lipids, and nucleic acids. The accumulation of these molecules is now widely associated with aging (Zeng et al., 2019). AGE’s are naturally formed in the human body over time. However, diet and lifestyle can accelerate the accumulation of these products and are associated with physiological decline (Zeng et al., 2019). AGE concentration is directly correlated with several deleterious skeletal muscle conditions, such as osteoporosis and arthritis (Nguyen et al. 2023). Glycation can permanently inhibit or alter the function of the molecules they affect. Additionally, glycation causes protein aggregation and inhibits clearance of these molecules by blocking tags that would otherwise be recognized and cleared by the immune system (Raghavan et al., 2024).
But what does it mean when we say glycation is a non-enzymatic reaction? Think about going for a swim in the ocean. You step a little too close to a crab, it uses its pincers to clamp down on your toe, and you must shake your foot to get him off. Enzymatic reactions are like that. The stimulus was you walking too close to the crab, which created a reaction, and he pinched you. But a non-enzymatic reaction is one that happens somewhat by chance, since it doesn’t require a stimulus or additional energy. You keep walking along and suddenly you bump into a jellyfish, and he attaches himself to you. The jellyfish didn’t target you, but because you collided the two of you are now stuck together. This is how glycation works. In this scenario you are the protein (or other macromolecules) and the jellyfish represents a sugar molecule. The more sugar molecules there are in your blood (or jellyfish in the ocean), the higher the likelihood that there will be a collision, and that the molecules will become stuck together. Now imagine trying to go for a swim if the whole ocean was filled with jellyfish. And imagine if every time you encounter a jellyfish, it stuck to your body for the rest of your life. That is what is happening to our hormones, DNA, and proteins, every time they experience glycation.
Glycation affects all areas of the body. Glycation of collagen proteins causes stiffening of tendons, skin, and vascular system. It alters proteins in the eye that affect the lenses, which plays a role in the impaired vision patients face in age-associated cataracts. And along with AGE’s role in diabetes, glycation is also associated with other life-threatening chronic diseases, including: hypertension, cardiovascular diseases, chronic kidney diseases, pulmonary diseases such as chronic obstructive pulmonary disease (COPD), neurological diseases such as Alzheimer’s disease, liver diseases, and cancer (Zeng et al., 2019).
As stated earlier, AGE formation is a naturally occurring process where sugars become attached to other macromolecules, and its accumulation in the body has been gaining interest as a biomarker of aging (Nguyen et al., 2023). This accumulation of AGE’s has been associated with physiological decline (Nguyen et al., 2023), several therapeutics have been proposed to inhibit or reduce AGE formation (Sourris et al., 2020). Along with pharmaceutical interventions such as aminoguanidine and OPB-9195, Vitamin B and it’s derivates have shown promising results in reducing age-lowering effects in clinical trials (Sourris et al., 2020). However, it is this author’s opinion that the most effective tactic for preventing the accelerated formation of AGE’s and glycation would be to regulate one’s blood glucose levels. Hyperglycemia has shown again and again to have detrimental health effects across a variety of conditions, and now we might be finding that the effect this has on AGE formation could be a significant underlying reason for them all.
References
Phuong-Nguyen, K., McNeill, B. A., Aston-Mourney, K., & Rivera, L. R. (2023). Advanced Glycation End-Products and Their Effects on Gut Health. Nutrients, 15(2), 405. https://doi.org/10.3390/nu15020405
Raghavan, C. T. (2024). Advanced Glycation End Products in Neurodegenerative Diseases. Journal of Molecular Neuroscience, 74(4). https://doi.org/10.1007/s12031-024-02297-1
Sourris, K. C., Watson, A., & Jandeleit-Dahm, K. (2020). Inhibitors of Advanced Glycation End Product (AGE) Formation and Accumulation. Handbook of Experimental Pharmacology, 264. https://doi.org/10.1007/164_2020_391
Zeng, C., Li, Y., Ma, J., Niu, L., & Tay, F. R. (2019). Clinical/Translational Aspects of Advanced Glycation End-Products. Trends in Endocrinology and Metabolism: TEM, 30(12), 959–973. https://doi.org/10.1016/j.tem.2019.08.005