
You might consider Heart Disease, Stroke, Cancer, Diabetes and Dementia as the leading causes of death and disability that accompany aging, but underlying all of these is a slow, subtle aging mechanism called Glycation. Glycation is the accidental bonding of sugars to proteins and fats to form Advanced Glycation End-products (or AGEs – a very appropriate acronym) which then accumulate in all the body’s tissues, slowly disabling their normal function. In time, all these popular diseases are directly fostered by the accumulation of AGEs in our various tissues and organs. The science of all this has been growing for the last 25 years, but doctors and health authorities have been slow adopters of the knowledge; drug companies and the food industry have resisted purposefully against revising the published ‘truths’ and acting against this powerful aging mechanism underlying all these diseases. The science is also quite complex, not easily grasped by the casual reader, but I want to try to explain it in street terms so we can begin taking strategic action against this killer.
Glycation – a primary mechanism of aging
Glycation is the accidental chemical bonding of a sugar molecule to a molecule of protein or fat. It happens outside the body in cooking (‘browning’ of anything, for example grilling meats, veggies or toast) and it happens inside the body in nearly every tissue because we use glucose (blood sugar) as a primary fuel for producing energy. All animals have developed mechanisms for sequestering AGEs and ushering them out of the body, but they don’t get them all. Some AGEs escape and are incorporated into our tissues, and accumulate over time. Our immune system progressively sees these as foreign enemies to be destroyed, and they become the primary cause of rising inflammation with age.
Blood Sugar level – the key parameter
The rate at which AGEs are formed is dependent on blood glucose levels; higher glucose yields higher AGE formation rates. Metabolism of glucose also creates residual chemicals called aldehydes (alcohol metabolism likewise produces aldehydes) and these are also agents of glycation. Glycation from dietary sugars such as glucose, fructose and galactose are the first of several steps to forming AGEs, with fructose and galactose being about 10 times more active than glucose. This is why High-Fructose Corn Syrup (HFCS) is perhaps the worst sweetener we can use. All the mechanisms forming AGEs are higher in diabetics, as are the rates of progression of the diseases associated with aging – it all happens faster in diabetics. One of the sources I have researched stated that many of the artificial sweeteners in use today also, even though non-caloric, are glycating agents (for instance: Aspartame is metabolized into formaldehyde in the liver and taken up several organs). The take home on this is that the higher our blood sugar, the faster we age, and the faster we acquire the diseases that are going to disable us and kill us.
Disease-specific damage: How glycation makes us sick
Heart disease: AGEs damage LDL cholesterol, glycating the apoB belt circling the molecule, making it more easily oxidized, smaller and more invasive to the inner lining (endothelium) of arteries and vessels. The endothelial cells respond directly by loosening their cohesiveness to one another making the layer more permeable to damaged LDL, starting the plaque-building process.
Endothelial cells have receptors for AGEs (called RAGE, as do most cells), which, when AGEs land on, signal the cell to up-regulate NFkB ( a nuclear gene switch that turns on inflammation signaling) and start an inflammatory cascade (basically tells our immune system to send macrophages and other immune cells to kill and eat the damaged cholesterol, but when they do so, they become foam cells and become part of the artery-inflaming, plaque-building process). Such sensitized cells also build more RAGE structures, becoming increasingly sensitive to AGEs, and more inflamed. AGE-modified LDL also invades the smooth muscle cells of arteries, stiffening their walls and raising blood pressure. At the same time, glycated HDL loses much of its ability to collect cholesterol from the plaque and eliminate it through the liver.
Now, with our youth drinking sodas at an early age, we see the process of arterial damage starting before adolescence. The point is that AGEs alarm our immune system, putting it in a state of hyper-alertness, causing chronic inflammation of many of the body’s tissues and organs.
Cancer: The nursery for cancer is inflamed tissues that are oxygen-deprived. Stiffening of the vascular system reduces oxygen supply to cells, inflammation from the immune system damages cells, and if not killed they may be damaged in ways that turn on genes that promote cancer. One would hope that the hyper immune system would recognize this change and kill the renegade cells, but cancer cells seem to be able to highjack functions of the immune system to help them grow and thrive. Glycation, oxidative stress and inflammation are mutual promoters; increasing any one increases the others, creating an escalating cycle of damage.
Dementia: AGEs that cross the blood-brain barrier are involved in damage of the brain’s blood vessels and in the miss-folding of ameloid-beta, leading to stroke, dementia and Alzheimer’s.
Connective tissue: AGEs bond to collagen, stiffening and destroying the elasticity of skin, tendons, ligaments and the fascia surrounding every element of our body. All our cells are imbedded in what is called the extracellular matrix which allows the movement of fluids, nutrients, waste products and signalling chemicals in and around all cells. AGEs slowly destroy these functions and invite the immune system to generally inflame our bodies. AGEs accumulate in our skin, caused by diet and excessive sun exposure, creating wrinkles, sags and loss of elasticity. Smoking floods the bloodstream with AGEs created on the hot end of pipes, cigars and cigarettes – there are few faster ways to look older than we actually are than smoking; and of course our insides are doing the same.
Strategies for minimizing glycation – slowing aging of every part of our body:
Keep blood sugar low: This is the key parameter to control. How do we do this? Consider the following:
What supplement can be used to hold down blood sugar/glycation?
What else holds down blood sugar?
Bottom Line: Adopt these dietary and exercise strategies and your aging rate will plummet. You will live a far more active life with less disability and likely attend most of your friends funerals before they attend yours.
Good Living – Frank
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