Hormesis of the AGEs

Some semi-random thoughts (ie, I might’ve had too much coffee haha)

-I’ve never really been a fan of the concept of “hormesis,” because you can basically say it of just about anything.  Kinda like “vestigial,” because, like, you technically don’t need your legs…

-We’ve seen actual human trials on AGEs, I even wrote a relatively mature blog post about ’em (this isn’t gonna be like that). Tl;dr: they really do some bad things in experimental settings. No, not bad like playing in traffic; bad like inflammation, oxidative stress, etc.

-Some say the ability to cook was a major evolutionary factor. Improved digestibility, nutrient bioavailability, energy extraction, reduced toxins, etc. I don’t know, maybe it was just seafood/DHA. Whatevs, I don’t really buy this line of reasoning anyway.  Maybe AGEs are not hormetic and are outright harmful; but cooking was better for our species because we died from other things long before the AGEs got us… or maybe this is a good reason to eat more baked mushrooms (as per Roncero-Ramos et al., 2016) haha.

-I follow the BTD (Blow Torch Diet™)* so seared meat and to a lesser extent plants can’t be unhealthy, right?

*seriously, I use this and these all the time.





Some papers on AGEs:

Hormetic modulation of hepatic insulin sensitivity by advanced glycation end products (Fabre et al., 2017)

AGE: glycosylated albumin. Not the most common dietary AGE (I think), but it wouldn’t surprise me if we had some floating around our bloodstream.

Method of delivery: injection into their stomach cavity. This doesn’t mimic endogenous or dietary AGEs.

In any case, weirdness ensued: they didn’t clamp ’em, but by all other measures insulin sensitivity worsened everywhere (as expected) except in liver (weirdness).

“AlbAGE induced whole-body insulin resistance concomitantly with increased hepatic insulin sensitivity, evidenced by activation of AKT, inactivation of GSK3, increased hepatic glycogen content, and decreased expression of gluconeogenesis genes. Additionally there was reduction in hepatic fat content, in expression of lipogenic, pro-inflamatory and pro-oxidative genes and increase in reactive oxygen species and in nuclear expression of NRF2, a transcription factor essential to cytoprotective response.”



Imma fan of NRF2. Maybe seared Brussels sprouts do it 🙂



Protein glycation – between tissue aging and protection (Simm et al., 2015)

“In summary, this indicates that protein glycation behaves like a double-edged sword. It induces tissue aging and degenerative diseases on the one hand, on the other hand, may also have protective effects, indicating a hormetic response.”




I don’t have the answer, but I feel as though if AGEs are important mediators of human health, there’s gonna be a big difference between the ones we eat (formed via cooking/searing meat) and the endogenous ones (formed via chronic hyperglycemia). Quantitatively, qualitatively, or otherwise.

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