The open access paper linked here reviews evidence for the contribution of dietary advanced glycation end-products (AGEs) to aging. There is in fact some debate over the degree to which AGEs from the diet are important in aging versus AGEs generated within and between cells. There are many types of AGE capable of forming cross-links in the extracellular matrix. These cross-links degrade tissue structure and function, and while most are short-lived and soon broken down, the less common long-lived varieties build up over the years to contribute to age-related disease and degeneration. The overwhelming majority of cross-links in old human tissues involve glucosepane, a long-lived AGE that doesn't appear to arrive in significant amounts from the diet. The SENS Research Foundation is funding programs to find a way to safely break down glucosepane since our evolved biochemistry isn't capable of performing that job. AGEs don't just form cross-links, however. They can also spur chronic inflammation and other bad cellular behavior by interacting with the receptor for AGEs, RAGE. This is an area in which short-lived AGEs and dietary AGEs might be contributing meaningfully to aging, and is certainly a day to day concern for people with diabetes, for example.
An important mechanism by which lifestyle influences loss of health and function is oxidative stress. Oxidative stress results in oxidized cell macromolecules and disturbs cell signal transduction, especially insulin-mediated metabolic responses. Metabolic insulin resistance remains a poorly understood phenomenon of cell stress associated with aging and chronic degenerative diseases. Medical approaches focus on management of hyperglycemia, often at the expense of insulin-dependent cell stress. Systemic advanced glycation end-products (AGEs) formed endogenously or acquired from high temperature-cooked foods and tobacco products are powerful pro-oxidants. Emerging research reveals the compelling contribution of dietary AGEs (dAGEs) to systemic load of AGEs, cell stress and insulin resistance.
Advanced glycation end-products promote oxidative damage to proteins, lipids and nucleotides. Aging and chronic diseases are strongly associated with markers for oxidative stress, especially advanced glycation end-products, and resistance to peripheral insulin-mediated glucose uptake. High advanced glycation end-products overwhelm innate defenses of enzymes and receptor-mediated endocytosis and promote cell damage via the pro-inflammatory and pro-oxidant receptor for advanced glycation end-products. Here we review emerging evidence that restriction of dietary advanced glycation end-products significantly reduces total systemic load and insulin resistance in animals and humans in diabetes, polycystic ovary syndrome, healthy populations and dementia. Of clinical importance, this insulin sensitizing effect is independent of physical activity, caloric intake and adiposity level.