AGEing gracefully 5. May 2010 William Davis (32) Advanced Glycation End-products, or AGEs, have the potential to change our entire conversation about diet. AGEs come from two principal sources: 1) Endogenous--Glucose-protein interactions that arise from high blood glucose levels 2) Exogenous--From diet The first is sensitive to glucose levels: the higher the glucose level, the greater the AGE formation. The second depends on the quantity of AGE in the food consumed.A compelling body of evidence points towards AGEs as an agent of aging, as well as kidney dysfunction, dementia, and atherosclerosis. Some of the observations made include:--If AGEs are infused into an experimental animal, it develops atherosclerosis, kidney disease, and other "diseases of senescence" within weeks to months. --In endothelial cells (cells lining arteries), AGE induces expression of adhesion molecules and inflammatory signals. In fibroblasts, AGE provokes collagen production. In smooth muscle cells, AGE triggers migration and proliferation. In monocytes and macrophages, AGEs induce chemotaxis and release of inflammation mediators. In short, AGEs have been implicated in just about every step leading to atherosclerosis.--In humans, greater quantities of AGEs are present in diabetics, pre-diabetics and people with insulin resistance. We all know that these people develop atherosclerosis, kidney disease, cataracts, and other conditions at an accelerated rate. --Foods containing greater quantities of AGEs cause endothelial dysfunction, i.e., artery constriction via blockade of nitric oxide and other mechanisms.Short of taking agents that block AGE activity, how can you minimize the absorption or production of AGEs? There are two general strategies:1) Keep blood glucose low--The Whitehall study demonstrated increased cardiovascular mortality with a postprandial (actually 2-hour post- 50-gram glucose challenge) blood sugar of 83 mg/dl. Lower blood glucose, less glycation. Less carbohydrates in the diet, the lower the blood sugar, the less the glycation. Studies like Whitehall demonstrate that glycation begins with glucose values within the normal range. Thus, aging occurs even with normal glucose levels. It occurs faster with higher glucose levels. 2) Choose and prepare foods with lower AGE content. Food content of AGEs is a major determinant of blood AGE levels. Fats and meats are the primary dietary source of AGEs, particularly if cooked at high temperature (broiling, frying). While this does not mean that meats and fats need to be avoided, it can mean that limiting serving size of meats and fats, while being selective in how they are prepared, are important. This can mean cutting your meats in thinner slices or smaller pieces to permit faster cooking, eating rare when possible (not poultry, of course), avoiding cooking with sauces that contain sugar (which enhances AGE formation). Is this an argument in favor of sashimi?Minimizing exposure to AGEs, endogenous or exogenous, has the potential to slow the aging process, or at least to lessen the likelihood of many of the phenomena of aging. More on this to come.