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:
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.
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!
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):
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):
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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There’s a nice table of AGEs in various foods here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704564/table/T1/
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Aren’t young bodies often better at eliminating dietary AGEs than older bodies?
Isn’t coffee full of AGEs and still pro longevity?
Coffee grounds have a lot of acrylamide, but for whatever reason, they aren’t found in the supernatant
why does olive oil contain a lot of CML when it’s nearly free of protein?
I find this unconvincing. How did researchers cut the dietary CML? Did they reduce the amount of vegetable oil they were fed? Mice chow is usually full of this and other refined things anyway. If they did remove something from the mice chow, what was used to replace it? If nothing replaced it, what were the adjusted macros?
This is an interesting study, but using it to say that I shouldn’t cook my meat at high temperatures is a stretch.
I’ll admit I didn’t read the study thoroughly, but from what I’ve read elsewhere on the internet, AGEs are broken down in digestion. I didn’t see any graphs here showing that the researchers observed a post-prandial increase of AGEs in the blood.
Both diets were the same except one group were fed more AGE products. And that was enough to shorten lifespan, even on a CR diet.
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So, if I get this right, we are extrapolating from a mouse study varying carboxy-methyl-lysine in their diet as proxy for human studies with human AGEs? It’s hard to know how representative this is but even harder to do human studies, so for now, let’s go with the effects of carboxy-methyl-lysine on mice and eliminate many ancestral foods and cooking methods to be safe, right?
My first response is that it’s a leap to so radically change our diets on this level of evidence.
But perhaps there is much more evidence now available in a variety of studies. Perhaps we can see some trend with humans?
In general, it’s easy to take a bit of knowledge, ignore the larger context (often a necessity in science to perform experiments), and then go ahead and extrapolate. It’s been done quite a lot and we often find out later that there were more factors in play than just the one we studied.
Thanks for reading the article, but you didn’t watch the embedded video, which details the impact of dietary AGE products on human health:
OK. Gotcha. Seems to affect IR in people, associated with some cancers and just might be important factor on lifespan.