Considering Dietary AGEs and Alzheimer's Disease

Advanced glycation end-products (AGEs) are involved in aging, as they can form cross-links that damage tissue structure, and trigger chronic inflammation via the receptor for AGEs. There are are many types of AGE and their influence is not all the same. Some can be broken down rapidly by our biochemistry, and some cannot. They can be manufactured in the body as a form of metabolic waste and also ingested in the diet, so there are two very different characteristics of AGE presence, one class that builds up slowly over time, and another that varies according to intake and ongoing clearance. Further, the types of AGE involved in the pathology of aging in shorter lived animals such as mice are very different to the important types in we longer-lived humans, something that sabotaged early efforts to build treatments that clear the AGEs that damage tissue. More recent initiatives focus on glucosepane as the important source of cross-links in human tissues.

The degree to which dietary AGEs are significant in aging is a topic for debate. On the whole it looks to be the case that the inflammatory consequences of short-lived AGEs are the more important set of mechanisms for that source:

Advanced glycation end products (AGEs) are a group of compounds that are combinations of sugars and proteins and other large molecules. They can be formed in the body, and there is a large body of literature on AGEs and Alzheimer's disease. However, AGEs are also formed when food is cooked at high temperatures or aged for a long time such as in hard cheese. AGEs increase the risk of various chronic diseases through several mechanisms including increased inflammation and oxidative stress. They can also bind to the receptor for AGEs (RAGE). RAGE transports beta-amyloid proteins across the blood-brain barrier and contributes to the development of Alzheimer's disease.

This study looked at the content of AGEs in national diets and clinical studies and compared total AGEs to Alzheimer's disease rates. For this purpose, the values for AGE for many types of food were taken from a study in which researchers cooked 549 foods by different methods and measured the AGE content of the cooked food. They found that the higher the cooking temperature, the higher the AGE content. For example, 100 grams of raw beef had 707 kU of AGEs, but 100 grams of roast beef had 6071 kU. In typical national diets, we found that meat made the highest contribution of AGEs, followed by vegetable oils, cheese, and fish. Foods such as cereals/grains, eggs, fruit, legumes, milk, nuts, starchy roots, and vegetables generally make low contributions to the total amount of AGEs in a diet, either because they are generally prepared at low temperatures or since they comprise smaller portions of diets.

"This epidemiological study supports our previous findings in animals and humans of an important role for dietary AGEs in Alzheimer's disease. We found that mice kept on a diet high in AGEs, similar to Western diet, had high levels of AGEs in their brains together with deposits of amyloid-β, a component of the plaques characteristic of Alzheimer's disease, while at the same time developed declines in cognitive and motor abilities. The mice fed a low AGE diet remained free of these conditions. In addition, clinical studies have shown that subjects with higher blood AGE levels, in turn resulting from high AGE diets, are more likely to develop cognitive decline on follow up."

Link: http://www.eurekalert.org/pub_releases/2015-02/ip-nsp020215.php

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