thpoughts this thread on AGEs?

[the MOUSE]

https://looksmax.org/threads/why-youre-aging-glycation-and-a-g-e-s-insidious-killers-of-your-body.1127273/

Introduction:
I can't believe there aren't any threads on this subject. This is a huge component of aging and, therefore, should be considered when employing anti-aging strategies based on diet and lifestyle.

Basically, glycation happens when sugar (glucose and fructose) binds with fats and proteins. These fats and proteins no longer function properly because the sugar damages them and makes them brittle. When this sugar-binding process is completed at the end of the Maillard reaction, the result is called an advanced glycation end-product (A.G.E.).

Maillard Reaction illustration:

1724362504858

Or more simply for the chemically illiterate:

1724362651868

You may think that the Maillard reaction is good because it results in delicious food, but this chemical reaction is occurring in our bodies all the time. We are gradually being cooked and browned on the inside and out, becoming brittle like the crust of bread.

Damage from A.G.E.s:
A.G.E.s wreak havoc on our bodies by causing the degradation of collagen and other soft tissues responsible for making us look young and feel healthy. Here is a study that explains it: https://www.sciencedirect.com/science/article/abs/pii/S0738081X10000428

1724337455240

1724337650659

As you can see in these images, A.G.E.s disrupt the collagen and elastin in the skin and cause oxidative stress. Also, A.G.E.s bind to receptors for A.G.E.s (called R.A.G.E.s) that are present in every cell in the body. When this happens, the cells' DNA can get damaged, and can also release chemicals that cause inflammation to try to fight A.G.E.s. Chronic inflammation, aka inflammaging, leads to premature aging. A.G.E.s also cause mitochondrial disfunction.

A more comprehensive list of damage from A.G.E.s:

• collagen loss
• elastin loss
• DNA damage
• Mitochondrial disfunction
• inflammation
• oxidative stress
• amyloid plaques in the brain (Alzheimer's)
• apoptosis (cell death)
• fatty liver
• insulin resistance
  Source: https://www.healthline.com/nutrition/advanced-glycation-end-products
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704564/

There are 2 kinds of A.G.E.s: endogenous and exogenous. Endogenous refers to A.G.E.s that are created in our own bodies with the sugar present in our bloodstream. Exogenous refers to those that are present in foods that we consume.

Endogenous A.G.E.s
Most serious looksmaxers know that sugar should be avoided, but sugar is even more destructive than most people here probably realize. As I said earlier, eating too much sugar will cause some of the sugar to bind to your body's healthy proteins and fats (glycation), which will then ruin them by turning them into A.G.E.s. Superficially, this will lead to wrinkles, dry skin, and sagginess in facial skin/fat. This is sometimes referred to as the "sugar sag." But there are more serious conditions that will start to develop over time. Here are some health problems that sugar has been shown to cause or exacerbate:

• Heart disease
• Type 2 Diabetes
• Cancer
• Cellular aging via telomere shortening
• Depression
• fatty liver
• inflammation throughout the body
  source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8839066/
  www.healthline.com
  11 Reasons Why Too Much Sugar Is Bad for You
  Experts believe that excess sugar consumption is a major cause of obesity and many chronic diseases. Here are 11 negative health effects of consuming too much sugar.
  www.healthline.com www.healthline.com

Therefore, whenever you eat, it's crucial to prevent huge spikes in your blood sugar levels. One of the surprising things I found is that during a meal, the order in which you eat each food on your plate impacts how sharply your blood sugar rises. According to this study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876745/ during your meals, you should eat the vegetables first, then the proteins & fats, and then the carbs/starches/sugars. The fiber in the vegetables will slow the rate that your body absorbs the sugar into your bloodstream. The study I linked showed a 73% reduction in blood glucose spikes when food was consumed in this ideal order compared to eating carbs first.

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Other things that cause elevated levels of blood sugar:

• stress
• sleep deprivation
• lack of exercise (or too much)
• dehydration
• smoking
  source: https://www.webmd.com/diabetes/causes-blood-sugar-spikes
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561544/ - This study in particular shows that stress can cause changes in your hormones that inhibit insulin's ability to lower the sugar in your blood. Chronic stress can actually induce hyperglycemia and eventually diabetes. If you're stressed out all the time from school, work, bad relationships, or a dangerous environment, then this is the mechanism of how you age from these stressors.

It also is beneficial to practice intermittent fasting so that your body spends less time in a state of elevated blood sugar levels each day. Autophagy from fasting can also help prevent the glycation process: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733682/

If your diet includes fruits and carbs, you should look up the glycemic index of the foods you eat to get an idea of which ones will cause glucose spikes. The glycemic index indicates how much your blood glucose levels will be impacted by the foods you eat. More thorough explanation: https://www.healthline.com/nutrition/glycemic-index
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Exogenous A.G.E.s
A.G.E.s are ubiquitous in the foods that most people eat in developed countries. They are virtually in ALL processed foods. Any kind of food that comes in a bag (like a bag of chips) or a box (like a box of cereal) has A.G.E.s in it. This is because most of these food products have vegetable oils (omega 6s) and added sugar, and are also cooked at high temperatures. Vegetable oils are PUFAs, or Polyunsaturated fatty acids, which means they are unsaturated fats that can oxidize and produce A.G.E.s when sugar binds to them. Saturated fats do not oxidize, so they are generally safer in the context of creating A.G.E.s. Additionally, any time food is cooked at extremely high temperatures, the sugar within it binds to proteins and fats in it (remember the Maillard Reaction shown previously).

You may think you're safe if you avoid processed food and instead focus on eating meat (I'm looking at all of you carnivores rn), but you're likely still damaging your body without realizing it. Unfortunately, meat is one of the highest sources of A.G.E.s, partially because the animals you're eating were likely fed processed food, corn, etc. Furthermore, the meat is usually cooked at temperatures that are too high. Meat that is browned, blackened, and charred during the cooking process is glycated meat. Cooking methods that create A.G.E.s include grilling, frying, baking, roasting, toasting, boiling, broiling, and microwaving.

The same reaction happens when you overcook other foods as well, such as grilled vegetables or a charred piece of toast.

One silver lining about exogenous A.G.E.s you consume in food is that only 10% of these make it into the bloodstream, and of that 10%, 60% is absorbed into bodily tissues. However, it's still unknown what happens to your digestive system that has to deal with the other 90%. Your gut microbiome will probably suffer. Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC21074/

Recommended max daily intake of A.G.E.s: Roughly 15,000 kilounits of A.G.E.s. Here is a website with a good breakdown of common foods with the amount of A.G.E.s in each: https://anti-ages.org/a-g-e-s-in-food-1 Here's a screenshot as an example:

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I may never eat bacon again.

It's disconcerting that foods that have very low amounts of A.G.E.s are usually foods that are high in carbs, yet carbs break down into sugar when you digest them, causing A.G.E.s to form in your body. It's a frustrating, lose-lose situation for us because A.G.E.s seem to be nearly impossible to avoid entirely. Nevertheless, there are some strategies you can apply to your lifestyle to combat aging from A.G.E.s.

Guide to minimizing Glycation and A.G.E.s in your body:
Methods to keep your blood sugar low and/or prevent your body from making endogenous A.G.E.s:

• Intermittent fasting
• Limit carbs/sugar in your diet
• Only eat a small amount of fruit, and avoid fruits that have a high glycemic index (and DO NOT drink fruit juice, which is highly concentrated with sugar and has no fiber that can protect you)
• Start a meal with vegetables, then protein/fat, then carbs/dessert (if you can't resist)
• Don't smoke
• Don't drink alcohol
• Live a healthy lifestyle in general (low stress, exercise, sleep, protect your skin from the sun, etc.)

Methods to reduce the amount of exogenous A.G.E.s you consume:

• Avoid all processed foods. Anything with vegetable oil (such as canola oil) and anything with high fructose corn syrup is terrible for your health long-term.
• Eat whole foods. Eat foods that are single ingredients (e.g. a tomato, instead of ketchup or tomato sauce), or whose ingredients you can recognize easily. If it has a litany of ingredients you've never heard of, it's probably bad.
• Avoid high temperature cooking like grilling, frying, broiling, toasting etc. Avoid eating blackened, charred meat.
• Cook your food using the following methods instead: poaching, steaming, stewing
• Eat foods high in flavonoids and antioxidants, such as vegetables and some herbs (see below for a list of helpful ones)

Supplements that can limit (and possibly reverse) the creation of A.G.E.s in your body:
Note that all of the supplements below are easy to find on amazon or other online retailers. You can get them from brands like Nutricost, NOW, Life Extension, Swanson, etc. Pick whichever brand you trust.

L-Carnosine: This is an antioxidant that can actually sacrifice itself to be glycated to protect the proteins and fats in your body from glycation. Carnosine is found naturally in meat, including our own bodies. Our carnosine levels naturally decline as we age.
These studies showed that L-carnosine inhibited glycation: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137727/
https://www.researchgate.net/publication/51492014_Skin_beautification_with_oral_non-hydrolized_versions_of_carnosine_and_carcinine_Effective_therapeutic_management_and_cosmetic_skincare_solutions_against_oxidative_glycation_and_free-radical_productio
link.springer.com
Carnosine and advanced glycation end products: a systematic review - Amino Acids
Advanced glycation end products (AGEs) are a cluster of heterogeneous molecules that are generated in a non-enzymatic reaction by the binding of sugars with amino groups of DNA, lipids and proteins. Carnosine is a naturally occurring dipeptide with antioxidant activity, which inhibits protein...
link.springer.com link.springer.com

Beta-Alanine: This is a precursor to L-carnosine. Some studies suggested that consuming beta-alanine increases the carnosine levels in your body more than if you eat carnosine directly. Beta-Alanine is usually taken as an exercise supplement because of how it helps increase the carnosine levels in muscles.
Studies: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257613/
aminoco.com
Beta-Alanine and Carnosine: Which Supplement Should I Take?
Beta-alanine and carnosine have a relationship worth exploring. Carnosine helps you reach peak performance during high-intensity exercise, and beta-alanine helps boost carnosine levels in muscle. With all the marketing claims of beta-alanine and carnosine supplements, there’s some confusion...
aminoco.com aminoco.com

Vitamin B complex, specifically:
Benfotiamine, which is a derivative of vitamin B1 that you can't get from your diet.
These studies support it's efficacy: https://pubmed.ncbi.nlm.nih.gov/16936154/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880246/

Pirydoxal-5'- Phosphate (Pyridoxamine or Pyridoxanine), which are derivatives of vitamin B6. Pyridoxal-5'-Phosphate is the active form of B6 in your body.
Studies: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770850/
https://www.jbc.org/article/S0021-9258(18)41224-0/fulltext

Alpha-Lipoic Acid: an antioxidant
Studies: https://pubmed.ncbi.nlm.nih.gov/18803954/
www.nature.com
Taurine, alpha lipoic acid and vitamin B6 ameliorate the reduced developmental competence of immature mouse oocytes exposed to methylglyoxal - Scientific Reports
Advanced glycation end products (AGEs) are the final products of the Maillard reaction, formed through the interaction of carbohydrates and proteins. Reactive dicarbonyl compounds such as methylglyoxal (MGO) serve as precursors for AGEs formation. Elevated levels of MGO/AGEs are observed in...
www.nature.com www.nature.com

Quercetin: a flavonoid
Studies: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409999/

Taurine: an important amino acid
Studies: https://www.nature.com/articles/s41598-024-66785-5

Luteolin: a flavonoid with anti-oxidative and anti-inflammatory properties
Studies: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706309/

Hesperidin: plant flavanone found in citrus fruits
Studies: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10792178/
https://ncbi.nlm.nih.gov/pmc/articles/PMC10086570/

Naringin: a flavonoid found in citrus fruits
Studies: https://www.sciencedirect.com/science/article/abs/pii/S096399692200415X

Turmeric (and Curcumin): a spice
Studies: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252471/
pubmed.ncbi.nlm.nih.gov
Curcumin against advanced glycation end products (AGEs) and AGEs-induced detrimental agents - PubMed
Curcumin can inhibit AGEs formation and AGEs-induced disturbances. More RCT researches are suggested to evaluate beneficial effect of curcumin regarding AGEs in different age-related chronic diseases, with specific attention to AGEs memberships.
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov

Honerable mentions: allspice, cloves, oregano, thyme, black pepper, cumin, cinnamon, parsley, ginger
Studies: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523868/

I did not include topical skincare products that could help with this because skincare threads have been done to death on this forum. The usual stuff will help, like tretinoin, vit c, etc. Glycation is more than just skin deep - it's an issue that needs to be addressed for the whole body so that you can be healthy and biologically young for longer.

Educational Videos:

Final Thought: I really think this is one of the main reasons why we age. We're all gradually glycating. The glucose that we use for energy is slowly ruining our bodies. If you want to look like a 25 year old mogger at 40, then you NEED to prevent this terrible process from killing your SMV.

Tagging high IQ users and/or old users interested in aging: @You @DrTony @Seth Walsh @Lawton88 @King Solomon @eduardkoopman @Jerryterry129 @AscendingHero @Gargantuan @enchanted_elixir @New Poster @Amnesia @Corleone @oldcell @mvp2v1 @garoupilled_ @forevergymcelling

Can't believe I finally have a chance at this honor: Best of the Best?

[Peatful]

Peat spoke of this

Advanced glycation is “treated” with carbon dioxide or co2

Carbon dioxide relaxes
And hence more o2 can be carried and utilized

This is from memory
Please fact check

[the MOUSE]

@Peatful hmmm

[izkrov]

Most AGEs happen because of PUFA.
https://www.jbc.org/article/S0021-9258(17)31047-5/fulltext

[A Former User]

@izkrov yes.

@the-MOUSE Another thing to consider is the roll that thiamine plays regarding PUFA and also with AGEs. This positive action of thiamine is a feature of thiamine in general, not just a single type.
The importance of thiamine (vitamin B1) in humans
"Moreover, thiamine is a potent inhibitor of advanced glycation end-product (AGE) formation by the non-enzymatic glycation of proteins by glucose [126]. These molecules contribute to both functional and structural modifications of many proteins, cellular dysfunctions and apoptosis, which leads to damage to tissues and organs. It can occur because of AGEs engagement in the production of reactive oxygen and nitrogen species, and also accompany oxidative stress and inflammation. Ultimately AGEs contribute to the pathological symptoms of diabetes mellitus, renal disease, cardiovascular disease, aging, and neurodegenerative diseases [127,128]. Thiamine has a protective effect against the development of the atherosclerotic plaque because it boosts endothelial functions and retards atherosclerosis progression [129]."

Thiamine is a powerful antioxidant that counteracts the effect of PUFA, but if there's too much PUFA, thiamine can be overwhelmed by it, causing a thiamine deficiency. see this one: The thiamine deficiency syndrome M74, a reproductive disorder of Atlantic salmon (Salmo salar) feeding in the Baltic Sea, is related to the fat and thiamine content of prey fish

"Thiamine, interacting directly with free radicals and hydroperoxides (Lukienko et al., 2000) also inhibits lipid peroxidation and free radical oxidation along with other antioxidants, functioning as a site-specific antioxidant (Gibson and Zhang, 2002). Therefore, generalized oxidative stress may reduce the levels of thiamine components and the enzymes that act on thiamine. On the other hand, thiamine deficiency in itself increases oxidative stress (Gibson and Zhang, 2002)."

@Peatful Thiamine acts as a carbonic anhydrase inhibitor so it increases CO2 both by optimizing oxidative metabolism (CO2 is the end byproduct when ATP is created) and also by keeping the CO2 from being broken down so quickly.
see here: Why does High-Dose Thiamine Relieve Fatigue in Individuals with Diverse Conditions? — Hypotheses Grounded in Thiamine’s Role as a Carbonic Anhydrase Inhibitor

[the MOUSE]

@mostlylurking thanks

[A Former User]

@the-MOUSE said in thpoughts this thread on AGEs?:

Here are some health problems that sugar has been shown to cause or exacerbate:

Heart disease
Type 2 Diabetes
Cancer
Cellular aging via telomere shortening
Depression
fatty liver
inflammation throughout the body
source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8839066/
www.healthline.com

I'd like to point out that your sugar consumption needs to be in sync with your thiamine status. Burning sugar for cellular energy requires thiamine because thiamine acts as an enzyme cofactor in the citric acid cycle (Krebs cycle). I suspected that all of the negative health issues in the list above are tied in with thiamine deficiency. I think that the core issue is thiamine deficiency, not sugar itself.

Heart disease: searched for "heart disease and thiamine"
this one: Thiamine and Cardiovascular Disease: A Literature Review
"Thiamine plays an important role in energy metabolism in the human body. Deficiency in thiamine has high prevalence in certain at risk populations, and it can lead to serious morbidity and mortality. The role of thiamine deficiency in causing endothelial dysfunction, vascular diseases, and systolic HF are well documented in the current literature. "

Type 2 Diabetes Searched for "diabetes and thiamine"
this one: Thiamine and diabetes: back to the future?
"The first reports of a link between thiamine and diabetes date back to the 1940s. Some years later, a role for thiamine deficiency in diabetic neuropathy became evident, and some pilot studies evaluated the putative effects of thiamine supplementation. However, the administration of thiamine and its lipophilic derivative benfotiamine for the treatment of this complication gained consensus only at the end of the ‘90 s. "

Cancer: searched for "cancer and thiamine"
this one is interesting: The Role of Thiamine in Cancer: Possible Genetic and Cellular Signaling Mechanisms
"A significant association has been demonstrated between cancer and low levels of thiamine in the serum. Genetic studies have helped identify a number of factors that link thiamine to cancer, including the solute carrier transporter (SLC19) gene, transketolase, transcription factor p53, poly(ADP-ribose) polymerase-1 gene, and the reduced form of nicotinamide adenine dinucleotide phosphate. Thiamine supplementation may contribute to a high rate of tumor cell survival, proliferation and chemotherapy resistance. Thiamine has also been implicated in cancer through its effects on matrix metalloproteinases, prostaglandins, cyclooxygenase-2, reactive oxygen species, and nitric oxide synthase. However, some studies have suggested that thiamine may exhibit some antitumor effects. The role of thiamine in cancer is controversial. However, thiamine deficiency may occur in patients with cancer and cause serious disorders, including Wernicke’s encephalopathy, that require parenteral thiamine supplementation. A very high dose of thiamine produces a growth-inhibitory effect in cancer. "

In other words, low dose thiamine may be carcinogenic, medium dose thiamine is a wash, and high dose thiamine is anti-cancer. Further study revealed that low dose = probably below 50mgs, medium dose = 100mgs-2500mgs; high dose = 3500mgs. But this could certainly vary between people. I cannot tolerate greater than 2000mgs of thiamine hcl daily; I got shooting electrical zapping pains in my thighs at night after trying 2500mgs of thiamine hcl.

Cellular aging via telomere shortening: searched for "telomere shortening and thiamine"
this one: Drinking makes you older at the cellular level
"We also found an association between telomere shortening and thiamine deficiency (TD)," said Yamaki. "TD is known to cause neuron impairments such as Wernicke-Korsakoff Syndrome. Although how exactly TD can cause neural impairments is unclear, it is well known that oxidation stress cause telomere shortening and, thus, it is possible that oxidation stress may also cause neuron death." edit: I think they mean Oxidative Stress, not oxidation stress.... A search for Oxidative Stress and thiamine yielded this: Thiamine leads to oxidative stress resistance via regulation of the glucose metabolism
"In conclusion, these findings suggest that extracellular thiamine leading to oxidative stress resistance have an impact on the regulation of glucose metabolism by shifting the energy generation from fermentation to respiration. "

Depression: searched for "depression and thiamine"
this one: Neurological, Psychiatric, and Biochemical Aspects of Thiamine Deficiency in Children and Adults
"With glucose being the primary fuel for energy production in the brain, it is not surprising that mitochondrial dysfunction and the consequent impaired glucose metabolism have been associated with several neurological and neurodevelopmental conditions (97) and major psychiatric illnesses, such as depression (98) and schizophrenia (99). The neurological symptoms in thiamine deficiency are similar to defects of PDH, which most frequently present as Leigh-like syndrome with basal ganglia involvement. Therefore, the nervous system, which is highly specialized in the use of glucose for energy generation, seems to be most vulnerable to PDHC deficiency due to TPP depletion. In the brain, the lower mitochondrial ATP production will limit the maintenance of membrane potential via the action of the Na+,K+-ATPase, thereby compromising nerve conduction and chemical synapses. Moreover, the increased oxidative stress due to the lower TKT activity will damage critical biomolecules, initiating lipid peroxidation and oxidative damage to proteins resulting in fragmentation, posttranslational modifications, and cross-linkings."

fatty liver: searched for "fatty liver and thiamine"
this one: High-dose vitamin B1 therapy prevents the development of experimental fatty liver driven by overnutrition
"Here, we tested the hypothesis that treatment with thiamine (vitamin B1) can counter the development of hepatic steatosis driven by overnutrition. Remarkably, the thiamine-treated animals presented with completely normal levels of intrahepatic fat, despite consuming the same amount of liver-fattening diet. Thiamine treatment also decreased hyperglycemia and increased the glycogen content of the liver, but it did not improve insulin sensitivity, suggesting that steatosis can be addressed independently of targeting insulin resistance. Thiamine increased the catalytic capacity for hepatic oxidation of carbohydrates and fatty acids. However, at gene-expression levels, more-pronounced effects were observed on lipid-droplet formation and lipidation of very-low-density lipoprotein, suggesting that thiamine affects lipid metabolism not only through its known classic coenzyme roles. This discovery of the potent anti-steatotic effect of thiamine may prove clinically useful in managing fatty liver-related disorders."

inflammation throughout the body: searched for "inflammation and thiamine"
this one: The importance of thiamine (vitamin B1) in humans
"In the cells of the immune system, the induction of an immune response (inflammation) is associated with a switch of metabolic energy production from glucose, from oxidative phosphorylation to aerobic glycolysis. Thiamine has general anti-inflammatory properties by dephosphorylating pyruvate dehydrogenase, which intensifies the conversion of pyruvate into acetyl-CoA; in addition, thiamine inhibits the breakdown of pyruvate to lactate. "