Aging is an inevitable process, and it is more than just adding numbers to your age, which is referred to as biological aging. It is the term that defines the physiological and functional deterioration of human cells and tissue due to the accumulation of damaging factors. The factors contributing to biological aging include lifestyle, nutrition, genetics, diseases, or other medical conditions. In this article, we are going to discuss glycans and their role in biological aging. Glycation is a nonenzymatic attachment of consumed sugars to the proteins or lipids in the human body. The sugars involved in glycation are fructose, glucose, or their derivatives. It is considered as one of the important factors contributing to biological aging. This bonding of sugars with proteins or lipids degrades them, resulting in the formation of advanced glycation end products (AGEs), biomarkers of aging, and the development of many chronic or degenerative conditions including, Alzheimer’s disease, diabetes, cardiovascular diseases, atherosclerosis, chronic kidney disease, and many others. All these play a role in the biological aging of humans.
What Are Glycans?
Glycan is a term used for complex sugars (carbohydrates) in free form or attached to any other molecule. Glycans are known to be one of the four building blocks alongside proteins, lipids, and nucleic acids. IUPAC (International Unit of Pure and Applied Chemistry) defines glycans as “compounds formed by a large number of monosaccharides linked glycosidically.” glycans can be attached to proteins or lipids and are also referred to as polysaccharides. The carbohydrate or sugar portion of glycoproteins, proteoglycans, or glycolipids (glycoconjugates) is glycan. There are two types of glycosidic linkages:
● N-linked: the glycan is linked to asparagine.
● O-linked: the glycan is attached to threonine or serine.
Every living organism has glycan as primary building blocks, and it has many essential functions. Glycan plays a role in immunity and many other processes required for cellular and tissue differentiation.
Glycation and Biological Aging
Biological aging is a complex process occurring over a period of time in every living organism resulting from the accumulation of cellular, molecular, and organ damage that leads to loss of functioning capacity and increases susceptibility to diseases. It is commonly observed that lifestyle changes can slow down biological aging. Biochemical changes and macromolecular damages that occur in aging and age-related conditions have glycation as a common event. But how does glycation play a role in biological aging? Glycation is a spontaneous endogenous aging mechanism that occurs with time. In this process, free reducing sugars are linked with free amino groups of DNA, proteins, and lipids, ultimately forming Amadori products. The Amadori products then undergo various rearrangement and irreversible dehydration reactions resulting in the formation of advanced glycation end products (AGEs). AGEs are seen to be accumulated in various age-related degenerative diseases and can be a source of cellular dysfunction. Glycation also causes impairment of tissue elasticity (blood vessels, tendons, and skin) and loss of protein function. Oxidative stress and hyperglycemia accelerate glycation in the body. It is the reason behind the pathogenesis of aging and diabetic complications such as diabetic vasculopathy. Glycated products cannot be removed from the body once formed, supporting the accumulation of metabolic waste leading to aging.
Role of Oxidative Stress in AGEs Formation
Oxidative stress is the main factor resulting in the formation and accumulation of AGEs and also plays a role in aging and progression of many chronic diseases. Oxidative stress is worsened by the generation of reactive oxygen species (ROS) from glycation and glucose autoxidation. Various studies have confirmed that a decrease in the body’s antioxidant capacity gradually with time results in biological aging. And with increased oxidative stress leading to increased glycation ultimately enhances the production of advanced glycation end products. It will lead to alteration in cellular function, cell damage, and death. Mitochondrial dysfunction is the most studied feature of aging. Mitochondria are the main source of ROS generation and their attack. This accumulation of ROS in mitochondria will lead to increased production of AGEs and can elicit inflammatory reactions in the body, causing worsening of pre-existing diseases.
AGEs and Biological Aging
The accumulation of glycated macromolecules, also known as advanced glycation end products, is the hallmark of aging. AGEs can be ingested by exogenous sources or are produced endogenously in the body. Environmental factors, lifestyle, and dietary choices directly influence the rate of AGE formation endogenously. AGE has been identified from tissues in various diseases, including diabetes, but they are also produced physiologically in the body. The number of AGEs cannot be determined only by their formation but also by their excretion or removal rate. They not only exert their deleterious effect directly but also exert by interacting with specific receptors.
Three mechanisms have been studied in which advanced glycation end products exert their effects on cells and extracellular matrix, contributing to aging and age-related disorders.
1. Glycation of ECM (extracellular matrix)
The extracellular matrix is one of the main targets for AGE. Accumulation and cross-linking between AGE and extracellular matrix alter its function and elasticity. This cross-linking of collagen and elastic fibers affects vascular functions, increases skin stiffness, and accelerates skin aging. AGE cross-linking with vascular collagen alters its function, structure, increases the risk of plaque formation, and causes hyperplasia of the basal membrane.
2. Glycation of Intracellular Proteins
Glycation of intracellular proteins results in cellular dysfunction and alters gene expression. For example, it impairs the activities of many essential antioxidant enzymes, including glutathione peroxidase, catalase, and glutathione reductase. Impairment of these antioxidant enzymes results in the build-up of oxidative stress. In addition, the proteolytic degradation of glycated molecules is also altered, which leads to the accumulation of glycated proteins. Other intracellular components, including lipids and DNA, can also be glycated with impairment in functions.
3. Interaction With AGE Receptors
As already said, that AGE also exerts effects by interacting with receptors, RAGE. The receptor is present in epidermal keratinocytes, human skin, endothelial cells, and dermal fibroblasts. AGEs interacting with RAGE induces a cascade of signals affecting cell cycle, proliferation, inflammation, gene expression, and extracellular matrix synthesis. RAGE has been shown to induce apoptosis, autophagy, aging, and decrease cellular proliferation.
Exogenous AGEs are ingested mainly by food. The effects of exogenous AGEs in the body are the same as mentioned above, and their role in aging has been demonstrated by various studies. Sugars cooked with proteins cause the release of significant amounts of AGEs. Dietary pattern with restricted intake of AGEs is the only way to reduce the accumulation of AGE in the body and slow biological aging.
How to Reduce Glycation, AGE Production, and Slow Down Biological Aging?
Since the formation of AGE is the main factor studied in the aging process and age-related disorders so any way to inhibit AGE production or to break and remove already formed AGE in the body will slow down the aging and eventually have many other health benefits.
Inhibiting or Preventing AGE Formation
There are several natural and synthetic substances known to inhibit AGE formation. Aminoguanidine has been identified as an inhibitor of AGE formation, and reports have also shown it to be effective against diabetic retinal, renal and neural complications. However, due to its side effects, it has very limited application in clinical practice.
Naturally occurring Vitamin B6, Pyridoxamine is also known to limit AGE production and also helps in the removal of ROS. Trials are still going to confirm its efficacy as an AGE inhibitor and age reversal.
Various herbal products are studied to be effective and safe antiglycation agents similar to aminoguanidine. For example, flavonoids belonging to the group of polyphenols have been reported to decrease AGE accumulation in cells and tissues.
Role of Nutraceuticals
Keeping in view the significance of oxidative stress in the formation of AGE, substances with anti-oxidative properties will have anti-glycation effects. Naturally occurring nutrients and vitamins (nutraceuticals) such as ascorbic acid, pyridoxal, niacinamide, selenium yeast, riboflavin, Trolox, and manganese have been shown to reduce glycation of albumin. In humans, supplementation of Vitamin C is shown to reduce protein glycation. Many herbs and spices, including ginger, rosemary, cinnamon, tarragon, cloves, and marjoram, also inhibit glycation of albumin in vitro. Blueberry extract is also studied to be a potent AGE inhibitor.
Dietary Modification and Caloric Restriction
Diet is one of the common factors resulting in the accumulation of AGEs and accelerates biological aging. Dietary restriction of glycotoxins can reduce systemic inflammatory mediators like TNF, CRP, and IL-6 (these are diabetogenic, proatherogenic, and nephrotoxic). Similarly, AGE’s dietary intake will induce systemic oxidative stress, RAGE expression, and lowers the levels of antioxidants in the body, leading to aging and age-related disorders. Processed foods and animal-based foods have a higher content of AGE as compared to whole foods.
It is also seen that cooking methods can reduce AGE formation. Cooking for a shorter time period, at a lower temperature, and with moist heat can keep AGE formation at lower levels. Cooking on ceramic rather than metal will also reduce AGE formation. If meat is cooked with acidic ingredients like vinegar, lemon, or tomato juice, the formation of AGE production is reduced by 50 percent.
Physical activity is vital to slow aging but also has many health benefits. In diabetics, it will improve glycemic control. Physical activity will reduce the accumulation of AGE, improve the body’s antioxidant mechanisms, and inhibit ROS production. A study showed that lifelong trained athletes had 21% less content of AGE in the patellar tendon as compared to untrained. The increased energy demand during physical activity will reduce the levels of intermediates available for glycation. By improving glycemic control, the formation and accumulation of AGE are reduced.
Biological aging is directly related to glycation and advanced glycation end products. The main factor enhancing AGE production includes oxidative stress that can be controlled by taking care of diet and lifestyle. Biological aging can be slowed down by slowing the production and accumulation of AGEs in the body’s cells and tissue. Although glycans are also essential in a limited amount, the excess can lead to cellular dysfunction, aging, and age-related disorders. Many chronic illnesses can be progressed, and biological aging can be accelerated if glycation is not improved by modifying diet and lifestyle.
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Author Brian Rose Founder and CEO
I know firsthand what it’s like to live a fast-paced, high-stress life. I spent twenty years as a Stockbroker and Military Police Officer, serving the country overseas and at the Atlanta Summer Olympics. For years, I felt over-stimulated, unfocused, and completely depleted of energy. I had lost my vitality and sense of self-care in pursuit of success. Unknowingly to me, my body and mind were trying to tell me that enough was enough. Despite the warning signs my body was giving me, I didn’t want to give up my ambitions. At this point in my life, I knew there had to be a way for me to work hard, maintain my health, and gain success, all at the same time.
This revelation led me on a journey that revealed to me how I could lead a life full of vitality and increased longevity, without giving up my dreams. Equipped with new energy and a fully powered mind, I created a company that could help others begin their neural enhancement journey to realize their biggest dreams. Built on the foundation of a passion for personal wellness and success, KIYA Longevity was born.
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