Glycation
Glycation
A factor in aging is glycation. It happens when glucose, the main sugar we use as energy, binds to some of our DNA, proteins, and lipids, leaving them unable to do their jobs. The problem becomes worse as we get older, causing body tissues to malfunction, resulting in disease and death.
Glycation may explain why studies in laboratory animals indicate that restricting calorie intake extends lifespan.
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Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars. They can be a factor in aging and in the development or worsening of many degenerative diseases, such as diabetes, atherosclerosis, chronic renal failure, and Alzheimer's disease.
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More on AGEs
What are AGEs?
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AGEs (Advanced Glycation End-products) are harmful compounds that form when excess protein and sugar bind together. These compounds prematurely age our bodies and have been linked to many different serious health concerns. Some experts believe that our AGE levels should be a medical marker just like how blood pressure, body mass index and blood sugar are.
AGEs are a product of a person’s lifestyle and habits. The foods we eat, the amount of sleep we get, the stress we experience, and the level of exercise we take part in all help determine our AGE levels. Even smoking contributes to AGE development.
The negative effects of AGEs have been validated in many different scientific studies over a span of many years (a few of which can be seen here).
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Where do AGEs come from?
AGEs form both endogenously (inside the body), and exogenously (outside the body).
AGEs are formed naturally inside our bodies when excess sugar and protein combine, and can also be ingested from the foods we eat. Foods that are high in AGEs include fried, processed, or sugary foods. Animal meats, especially red meats, are also high in AGEs. They also form inside our bodies depending on our lifestyle. A sedentary lifestyle is one of the major contributors to high AGE levels, whereas regular exercise and physical activity helps reduce the amount of AGEs in our body. High levels of stress and a lack of sleep also contribute to AGE development.
AGEs are also formed outside of the body, such as on food. In fact, cooking methods affect AGE levels in the foods we eat, and AGEs can be consumed. Cooking with high levels of heat or using cooking methods that brown foods – including barbecuing, grilling, frying, sauteing, broiling, searing and toasting – send the AGE content of foods skyrocketing. That browning reaction even takes place during bread baking (namely with the crust), and the production of processed foods and dark sodas.
Conversely, using water while cooking helps reduce the formation of AGEs. Moist cooking methods such as boiling, steaming, poaching, stewing or simmering are all healthier than using high, dry heat (i.e. grilling). Still, acidic marinades can suppress AGE formation by up to 50 percent when cooking meat. Also, natural foods and ingredients are lower in AGEs than processed foods. Some natural produce (such as noni fruit, blueberries, olive leaves, cranberries and cornelian cherries) even contain phytonutrients knows as iridoids, which have been shown to reduce AGE levels in the body.
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How do AGEs affect the body?
The body has natural processes to rid itself of harmful AGEs. However, when too many AGEs are consumed and created, they build up faster than the body can keep up with and begin to accumulate in body tissues. This accumulation affects our entire bodies, from the skin to the organs.
AGEs damage the collagen and elastin in our skin, leaving it wrinkled, saggy and dull. This leads to an older physical appearance.
Meanwhile, high levels of AGEs are linked to virtually every serious health concern we face today: cardiovascular disease, diabetes, liver disease, Alzheimer’s disease, kidney function, blood sugar levels, joint health, memory function, vision impairment, inflammation, hypertension, heart disease, dementia, stroke, arthritis, osteoporosis and periodontal disease. Researchers have even discovered a potential link between AGEs and cancer.
For these reasons, it is very important that people are aware of their AGE levels (which can be measured through these methods) and take the necessary steps to lower them. And if someone already has low AGE levels, it’s important to maintain them.
Cellular Senescence: Deciphering the Impact on Aging and Health
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Cellular senescence, a fundamental aspect of the aging process, has become a key focus in the quest to understand and potentially reverse the effects of aging. This phenomenon occurs when cells cease to divide, entering a state of permanent growth arrest. While initially a protective mechanism against cancer, the accumulation of these senescent cells over time contributes significantly to the aging process and the development of age-related diseases.
Recent breakthroughs in this area have been transformative. Studies have shown that senescent cells secrete various pro-inflammatory chemicals, known collectively as the senescence-associated secretory phenotype (SASP). These chemicals not only contribute to the deterioration of nearby healthy cells but also play a role in
chronic inflammation, a known factor in many age-related conditions such as arthritis,
heart disease, and Alzheimer's.
Key findings have highlighted the potential of therapies targeting senescent cells, often referred to as ;senolytics;. These treatments aim to selectively clear senescent cells, thereby reducing their detrimental effects. Research has demonstrated promising results in animal models, showing improvements in healthspan, the delay or reversal of several age-related pathologies, and even extension of lifespan.
Moreover, understanding the triggers and pathways leading to cellular senescence is providing insights into preventive strategies. Lifestyle factors such as diet, exercise, and stress management have been found to influence the onset of cellular senescence, suggesting that lifestyle interventions could be a viable approach to delay the aging process and improve overall health. In essence, the study of cellular senescence is not only reshaping our understanding of the biological aging process but also opening new horizons for anti-aging interventions, with the potential to significantly impact human health and longevity.
Possible Remedies
Caloric restriction and dietary measures
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As nutrition is an important factor in aging, dietary caloric restriction may be effective in preventing accumulation of AGEs in the human body. In mice restriction of caloric intake increases lifespan and delays many age-related dysfunctions by altering stress response and influencing the expression of various metabolic and biosynthetic genes. Dietary restriction could significantly decrease the levels of AGEs in rat and mice skin collagen. Skin collagen glycation and glycoxidation inversely correlated with lifespan whereas caloric restriction led to decreased accumulation of AGEs and increased lifespan.
Dietary restriction may not be a pragmatic option in humans; however a restriction in intake of dietary “glycotoxins” may be more feasible.
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Foods that are high in AGEs that should be avoided/limited include:
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Sugary foods such as sweets, cookies, cakes, soda, and pastries
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Processed foods, including packaged meats and cheese
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High-fat (especially red) meats
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Fat, including butter, margarine, and oil
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Fried foods
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Prepare your food to limit AGEs formation :
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Don't :brown foods by grilling, frying, broiling, or sauteing - this actually creates even more AGEs.
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Do :use slow-cooker
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Do : cook foods in water through boiling, steaming, or poaching
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Do : marinate foods in acidic or citrus-based sauces
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Nutriceuticals
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Since oxidation steps are crucially involved in formation of many AGEs, substances with antioxidative or metal chelating properties, may also have antiglycating activities
Accordingly, an increasing list of natural antioxidants and chelating agents such as ascorbic acid, α-tocopherol, niacinamide, pyridoxal, sodium selenite, selenium yeast, trolox, rivoflavin, zink and manganese has been shown to inhibit glycation of albumin in vitro. Alpha-lipoic acid was able to reverse tail tendon collagen glycation in fructose-fed rats, an effect which was attributed to its endogenous antioxidant action, its ability to recycle ascorbic acid, α-tocopherol and GSH as well as to its positive influence on glucose uptake and glycaemia. Green tea, vitamins C and E and a combination of N-acetylcystein with taurine and oxerutin could inhibit skin collagen glycation in mice. Another compound, the green tea-derived polyphenol and flavonoid epigallocatechin-3-gallate revealed also promising in vitro effects by antagonizing AGE-induced pro-inflammatory changes. In healthy human subjects, supplementation of vitamin C significantly decreased serum protein glycation.
Many spices and herbs were shown to inhibit glycation of albumin in vitro, among them ginger, cinnamon, cloves, marjoram, rosemary and tarragon. Their protective effects correlated with their phenolic content. Recently, in vivo beneficial effects of some of these compounds were shown in zebrafish.
Other promising compounds include blueberry extract and naturally occurring flavonoids, such as luteolin, quercetin and rutin, which can inhibit various stages of AGE formation. Recently, blueberry extract, an AGE-inhibitor and C-xyloside, a glycosaminoglycan synthesis stimulator, were tested for 12 weeks in female diabetic subjects. This treatment resulted in significant improvement of skin firmness, wrinkles and hydration although it failed to show a significant decrease in the cutaneous content of AGEs.