15 replies to this topic

[Nate-2004]

An article posted last week on the Buck Institute's website:

 

https://www.buckinst...elated-disease/

 

 

An inevitable by-product of metabolism, advanced glycation end products (AGEs) are toxic molecules formed when proteins, DNA and fats become bound after exposure to sugar.  They are also in some of the foods we eat.

 

I put together a spreadsheet of foods (sourced here) and their AGE content. Some of the foods high in AGEs were incredibly surprising to me. I did not know butter on its own was high in AGEs, nor did I think Cheese, parmesan especially, would be so high. Other surprising things: Extra Virgin Olive oil is fairly high in AGEs, along with numerous raw nuts and seeds. Baffling.

 

Notes from source:

The heat-induced new AGE formation in olive oil was completely prevented in the presence of the AGE inhibitor, aminoguanidine, but only partly blocked by the anti-oxidant BHT (Table 2). The amelioration of new AGE formation by the AGE inhibitor aminoguanidine compared to the anti-oxidant BHT suggests that the process seems to be driven by glycation rather than oxidation.

New AGE formation in cooked meat was also inhibited following exposure to acidic solutions (marinades) of lemon juice and vinegar. Beef that was marinated for 1 hour in these solutions formed less than half the amount of AGEs during cooking than the untreated samples (Figure).

 

We should definitely be involving aminoguanadine in all types of food manufacturing.

 

Edited by Nate-2004, 12 September 2018 - 02:48 PM.

[OP2040]

I saw this same list as part of a study.  It does not instill confidence that limiting dAGE's will be helpful at all.  After all, olive oil and parmesan cheese are anti-aging superfoods in their own right.  It may be better to focus on the in vivo production of crosslinking that occurs partly due to AGE's and partly due to pre-existing age-related dysfunction.  You are right in that simply adding certain things to cooked foods will dramatically decrease the amount of dAGE's.  This also seems a better option than eliminating foods.  Almost any spice, vinegar or vegetable are very helpful in reducing AGE formation.  A great example of why Asian stir fries are quite healthy even with meat, whereas barbecue is notoriously unhealthy.  The stir fries have tons of veggies and spices to counteract not only AGE's but other nasties.

 

It's really sad how slow this is progressing.  I read something about Rosmarinic Acid being the most effective breaker, but again not for glucosepane which is the biggest one.  I have to believe that there is some in vivo mechanism for dealing with AGE's.  After all, oogenesis, regenerating animals and negligibly senescent animals must have to deal with this issue in some way.  My understanding is that the reason glucosepane is hard to break is because of its very long turnover time.  Perhaps since studies are limited by time, glucosepane would be broken by some of these substances, but over the course of a longer time period.  Just trying to determine if it's worth taking any of them or not. 

 

I just read the wiki article on Glucosepane, and they offer the following snippet:

 

"Two thiazolium molecules, PTB (N-phenacylthiazolium bromide)^[29] and ALT-711,^[30] have demonstrated success at reducing glucosepane levels in rats."

 

I was under the assumption that the problem for humans was exactly that glucosepane was the problem for humans, and that other breakers that worked in animals don't work in humans because they don't address glucosepane.  If this statement is true, and everything else we supposedly know is true, then these two substances should work in humans, no?

[Phoebus]

great spreadsheet!

 

looks like all meats are high in AGE, but salmon is low, also clearly frying, breading, BBQ-ing etc drastically increases AGE content in meats. 

 

big overlap between foods high in AGE and those high in acrylamide

 

coffee is virtually free of AGE

 

salmon with rice and beans and some kind of tomato sauce/salsa, a green salad, with coffee would make a delicious, very low AGE, meal. 

[Nate-2004]

I would like to know more about the methods of using aminoguanadine in oil production. I assume a lot of oils are CO2 extracted these days. How would aminoguanadine be used in such cases? Because I like peanut butter. What about extra virgin olive oil? EVOO seems outrageously high in AGEs. WTF is up with that?

Edited by Nate-2004, 12 September 2018 - 06:21 PM.

[Mind]

I think there is a thread about dietary AGEs vs. endogenously created AGEs. Do ALL of the dietary AGEs end up in the blood stream/cells?

[Phoebus]

looks like if you want to consume nuts RAW is the way to go for sure 

 

 

 Agric Food Chem. 2011 Nov 23;59(22):12037-46. doi: 10.1021/jf202515k. Epub 2011 Oct 20.

 

Determination of advanced glycation endproducts by LC-MS/MS in raw and roasted almonds (Prunus dulcis).

 

Abstract

 

A sensitive and reliable LC-(ESI)MS/MS method was developed and validated for the simultaneous analysis of five common advanced glycation endproducts (AGEs) after enzymatic digestion in raw and roasted almonds. AGEs included carboxymethyl-lysine (CML), carboxyethyl-lysine (CEL), pyralline (Pyr), argpyrimidine (Arg-p), and pentosidine (Pento-s). This method allows accurate quantitation of free and AGE-protein adducts of target AGEs. Results indicate that CML and CEL are found in both raw and roasted almonds. Pyr was identified for the first time in roasted almonds and accounted for 64.4% of free plus bound measured AGEs. Arg-p and Pento-s were below the limit of detection in all almond samples tested. Free AGEs accounted for 1.3-26.8% of free plus bound measured AGEs, indicating that protein-bound forms predominate. The roasting process significantly increased CML, CEL, and Pyr formation, but no significant correlation was observed between these AGEs and roasting temperature.

 

Edited by Phoebus, 15 September 2018 - 03:17 PM.

[OP2040]

The AGE issue seems to bring out the various contradictions and paradoxes much more than other theoretical causes of aging.  Eating AGE's cannot be that bad for you, by definition, if things like olive oil or roasted coffee are included in the category of "high-damage" exogenous AGE's.  These things are quite clearly beneficial to long-term health, and so the theory of AGE's must be revised in some way.  Either eating AGE's is no big deal, or maybe eating them with veggies completely neutralizes any effect, or possibly gut health has an effect.  Whichever way you spin it, AGE's end up way down the priority list for aging.  Just one beneficial intervention in mice would change my mind on this, but so far we have nothing.  A good metaphor for AGE's can be gleaned from Alzheimer's research.  Just like amyloids have turned out to be a total dud in targeting the actual disease, where processes seem to be the determining factor.  In Age's and crosslinks, it is also most likely a process that governs all of these various effects.  This is the gist of my problem with the damage theory of aging in general, it is far too simplistic in terms of theory demonstrated by the terrible "old car" metaphor, and far too complex in terms of possible interventions.

[Phoebus]

 Eating AGE's cannot be that bad for you, by definition, if things like olive oil or roasted coffee are included in the category of "high-damage" exogenous AGE's.  

 

 

thats the thing I cant understand. Med diet is proven to benefit longevity..however... its high in olive oil, therefore high in AGEs. 

 

something doesn't add up. ONe possibility is that even though the Med diet includes a high AGE item like olive oil, still OVERALL its still low in AGEs vs. other types of diets. 

 

SAD is loaded with AGEs for instance and we know SAD promotes diabetes, obesity and death. 

Edited by Phoebus, 15 September 2018 - 04:48 PM.

[OP2040]

Another example is the Turkish or Middle Eastern Diet, which is very similar to the med diet and possibly considered under that label.  Aren't dry grilled meats a big part of that diet?   My point is that the damage theory of aging is fundamentally negative and has everyone chasing their tails going after an almost endless supply of possible damages.  The human body is not a car, it operates on processes that can very easily clear damage when they are working correctly.  ROS and senescent cells are just as much processes as they are things that contribute to bodily damage. 

 

There are good reasons why people focus on these as damaging things.  First, it is much easier to eliminate a thing from the body, than to intervene in a complex process.  That's why antioxidents and senolytics, for whatever they prove to be worth, are some of the first anti-aging strategies.  Secondly, it is much easier to see and measure the damaging end-results of a decades long process than to track the point at which things initially tip in favor of aging.  In short, it is just easier, low-hanging fruit.  Contrast this with epigenetics.  It is much more complicated to intervene here because you have to target gene expression, which is a process not a damaging molecule.  But it is my firm belief that this will be the final word on aging.  If the epigenetic process can be reversed safely, cells made literally younger, then the process that starts in the embryo can be mostly recapitulated in an adult organism. 

 

Where would AGE's show up on the map if aging is an epigenetically programmed process?  I'm not convinced they will show up at all as something that needs to be targeted.  A young cell knows how to organize it's environment just fine during youth, given the proper signalling and expression mechanisms.  It also knows how to clean up any damage that occurs during oogenesis.

 

 

[Nate-2004]

I was reading through a somewhat recent study on the hypothalamus and aging and came across a paragraph stating that AGE crosslinks were diminished in the experiment:

 

In another provocative study, inflammation associated with increased NF-Kb activity was observed with increasing age in the MBH region of the hypothalamus. Ectopic expression of an inhibitor of pro-inflammatory NF-Kb/IKKb signaling in the MBH region of the hypothalamus increased life span in male mice. A dominantly acting IκBα driven by the microglial-specific CD11b promoter using lentiviral vectors injected into the MBH region of the hypothalamus increased lifespan by 23% in male mice and decreased aging-related dysfunction in the nervous system and skeletal muscles: increasing neurogenesis, skin thickness, bone density, while decreasing collagen crosslinking. Increased NF-Kb reduced expression endocrine factor GnRH by 2 fold. GnRH treatment attenuated the aging-associated phenotypes[3]. One potential caveat is that female mice were not studied in the lifespan extension studies, but responded similarly phenotypically.

 

 

Attached Files

•  mendelsohn2017.pdf   706.26KB   4 downloads

[Nate-2004]

Here's the deal I think. 

 

So high fat diets contain a lot of AGEs which can lead to cardiovascular disease while low fat diets are typically high in carbs, which can lead to obesity, type 2 diabetes, insulin problems, etc. 

 

The reason why the Mediterranean diet may be the most beneficial is likely because it is a sort of compromise between the two extremes. Beans and plant based foods are low in AGEs and have a low GI. Olive oils and fish are high in fat but may help with inflammation and satiety. 

 

I see Tofu and other "meat substitutes" are also high in AGEs so it's largely the case that a purely raw vegetable diet may be the healthiest but the least attractive alternative.

 

The reason why nuts and seeds or anything for that matter, are so high in AGEs is because of the fats. It's strange that despite this, nuts and seeds are repeatedly shown to prevent cardiovascular disease. Why though? 

Edited by Nate-2004, 18 September 2018 - 06:01 PM.

[Mind]

The benefits of olive oil and nuts must greatly outweigh the negatives (AGEs).

[OP2040]

The med diet is just more proof that AGE's are not super-important, and that focusing on damages, rather than regenerative processes, is not the way to go about things.  A lot of the things in the med diet are active promoters of certain processes, which then get upregulated to prevent or clean up existing damage.  Even the calorie restriction thing ONLY works because it effects a positive process, not because it limits damage. 

[Phoebus]

 

Anti-glycation Effect of Gold Nanoparticles on Collagen

Abstract

 

Gold nanoparticles (GNPs) have been reported to exhibit a variety of biological effects including anti-inflammatory and anti-oxidant activities. The extent of an in vitro glycation reaction mixture of collagen and glycolaldehyde was assayed to investigate the inhibition of glycolaldehye-derived advanced glycation end products (glycol-AGEs) formation with GNPs in collagen, which is a major protein component of the human dermis. -

Gold nanoparticlestreated collagen showed significantly less glycation (56.3±4.2%) than an untreated glycation control. Moreover, GNP-treated glycation in a collagen lattice model significantly decreased the AGEs distribution in the model system. Taken together, these results suggest that GNPs have the potential for use in the prevention of glycation-induced skin aging.

 

 

Edited by Phoebus, 02 October 2018 - 01:30 PM.

[Nate-2004]

Anti-glycation Effect of Gold Nanoparticles on Collagen

 

I read the full text. It's in vitro. I don't know how this would be done in vivo.

[GABAergic]

aminoguanadine is not used for anything anymore. it is non existent so how the hell would you even try using it at this point?