Tag Archives: AGE products

AGE Products Impact Lifespan: Impact Of Hyperglycemia, Kidney Function, And The Microbiome

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Papers referenced in the video:

Oral glycotoxins determine the effects of calorie restriction on oxidant stress, age-related diseases, and lifespan https://pubmed.ncbi.nlm.nih.gov/18599606/

Reduced oxidant stress and extended lifespan in mice exposed to a low glycotoxin diet: association with increased AGER1 expression https://pubmed.ncbi.nlm.nih.gov/17525257/

Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N 6-carboxymethyllysine https://pubmed.ncbi.nlm.nih.gov/35241804/

Plasma Carboxymethyl-Lysine, an Advanced Glycation End Product, and All-Cause and Cardiovascular Disease Mortality in Older Community-Dwelling Adults https://pubmed.ncbi.nlm.nih.gov/19682127/

Advanced glycation end products and their circulating receptors predict cardiovascular disease mortality in older community dwelling women https://pubmed.ncbi.nlm.nih.gov/19448391/

Acute Hyperglycemia Causes Intracellular Formation of CML and Activation of ras, p42/44 MAPK, and Nuclear Factor KappaB in PBMCs https://pubmed.ncbi.nlm.nih.gov/12606501/

Experimental Hyperglycemia Alters Circulating Concentrations and Renal Clearance of Oxidative and Advanced Glycation End Products in Healthy Obese Humans https://pubmed.ncbi.nlm.nih.gov/30823632/

Novel associations between blood metabolites and kidney function among Bogalusa Heart Study and Multi-Ethnic Study of Atherosclerosis participants https://pubmed.ncbi.nlm.nih.gov/31720858/

Serum Carboxymethyl-lysine, a Dominant Advanced Glycation End Product, is Associated with Chronic Kidney Disease: the Baltimore Longitudinal Study of Aging https://pubmed.ncbi.nlm.nih.gov/19853477/


Dietary AGE Products Impact Insulin Resistance, Inflammation, And Lifespan

Cooking foods at temperatures higher than boiling produces advanced glycation end (AGE) products, which induce insulin resistance and inflammation, and shorten lifespan in mice. Similar data exists in humans for the effect of dietary AGE products on insulin resistance and inflammation, and a higher dietary AGE product intake is associated with cancer in both men and women. Accordingly, reducing dietary AGE product intake may be an important strategy for improving health and increasing lifespan in people.

Be Careful How You Prepare Your Food: Advanced Glycation End Products Shorten Lifespan!

Dietary advanced glycation end products (AGEs) are formed as a result of the heat-induced (greater than 100C) binding of sugar to protein, fat or nucleic acids (DNA or RNA). The common way to identify AGE products in food is the browning effect: deep-frying, broiling, roasting, and grilling each produce a temperature that is sufficient to greatly increase AGE product formation, relative to either raw or boiled food.

The importance of dietary AGE products is that they shorten lifespan! Cai et al. (2007) quantified the amount of one particular type of AGE product, CML (carboxy-methyl-lysine) found in the mouse diet, and then fed mice half of this amount. The low-CML diet was sufficient to significantly extend median and maximal lifespan by 15% and 6%, respectively:

age lifespan

As shown below (inset), no difference in food intake was observed when comparing the 2 groups-from this it can be concluded that the lifespan extending effect of the low-CML diet was not related to a reduction in calorie intake. Also, mice on the low-CML diet had significantly decreased body weight, evidence that shows that it isn’t just calories that we should be worried about in terms of body weight maintenance.

age bw food intake

Dietary AGE products also shorten lifespan on a calorie-restricted diet. Calorie restriction is the gold standard in terms of minimizing disease risk and extending longevity in a variety of organisms, including worms, flies, mice, dogs, and monkeys. Because CR mice eat less food than controls, the possibility existed that CR-fed animals also ate less AGE products. To address this possibility, Cai et al. (2008) quantified the amount of AGE products that CR-fed mice consumed, and then increased this amount to either equal to or greater than what mice on a regular diet ate. In terms of lifespan, mice on a low AGE, low calorie diet had increased average and maximal lifespan, relative to mice on a regular, ad libitum diet. However, lifespan was significantly reduced for CR-fed mice whose food was supplemented an AGE product amount that was equal to the regular diet!

cr age less

These data suggest that if you eat less calories than normal, you will live longer, but, if your lower-calorie diet is poor in quality (i.e. high in AGE products), you will lose the lifespan extending effect of CR.

In support of the hypothesis that AGE products are bad for lifespan, dietary supplementation with glycated albumin (left) and fructosylated albumin (right) also shorten lifespan, in flies (Tsakiri et al. 2013):
fly lifespan glycation

To illustrate how cooking food at a high temperature impacts AGE formation, shown below is the AGE product (CML) content for a variety of foods (Goldberg et al. 2004):
age list
For example, boiling beef (as in a chili recipe), compared with roasting it results in ~3-fold less AGE products. Boiling egg yolks results in about half as much CML when compared with frying. Interestingly, olive oil has more than double the amount of CML, when compared to broiled chicken or beef!  Finally, fruits and vegetables such as bananas, apples, carrots, and green beans have almost negligible amounts of CML.

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Cai W, He JC, Zhu L, Chen X, Wallenstein S, Striker GE, Vlassara H. Reduced oxidant stress and extended lifespan in mice exposed to a low glycotoxin diet: association with increased AGER1 expression.Am J Pathol. 2007 Jun;170(6):1893-902.

Cai W, He JC, Zhu L, Chen X, Zheng F, Striker GE, Vlassara H. Oral glycotoxins determine the effects of calorie restriction on oxidant stress, age-related diseases, and lifespan. Am J Pathol. 2008 Aug;173(2):327-36.

Goldberg T, Cai W, Peppa M, Dardaine V, Baliga BS, Uribarri J, Vlassara H. Advanced glycoxidation end products in commonly consumed foods. J Am Diet Assoc. 2004 Aug;104(8):1287-91.

Tsakiri EN, Iliaki KK, Höhn A, Grimm S, Papassideri IS, Grune T, Trougakos IP. Diet-derived advanced glycation end products or lipofuscin disrupts proteostasis and reduces life span in Drosophila melanogaster. Free Radic Biol Med. 2013 Dec;65:1155-63.

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