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Home > Anti-aging Research > AGEs

Advanced Glycation End Product (AGE) inhibitors

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  • Long lasting protective effects of early l-arginine treatment on endothelium in an in vitro study - Clin Nutr 2021 Mar 3 - "Excess nutrient supply, such as high fat and high glucose intake, promotes oxidative stress and advanced glycation end products accumulation. Oxidative stress and AGE accumulation cause pathological elevation of arginase activity and pro-inflammatory signaling implicated in endothelial dysfunction. Several studies showed positive effects of l-arginine supplementation in endothelial function but little is currently known about the role of l-arginine as prevention of endothelial dysfunction caused by excessive nutrient supply (overfeeding). Our aim was to evaluate a possible protective effect of l-arginine on endothelial dysfunction caused by excessive nutrient supply (overfeeding), using human endothelial cells line in an in vitro study ... Endothelial EA.hy926 cells were pre-treated with 1.72 mM of l-arginine for 24 h and afterwards subjected to nutritional stress (high lipid, high insulin and high glucose concentrations) for further 24 h ... l-arginine pretreatment reduces AGEs generation ... An early l-arginine treatment is able to prevent oxidative stress and AGEs accumulation caused by overfeeding in human endothelial cell line by regulating STAB1/RAGE gene expression and by reducing excess arginase activity. The positive effects of l-arginine pretreatment continue even after treatment discontinuation in normal conditions" - See l-arginine products at Amazon.com.
  • The therapeutic effect of ALT-711 on erectile function in rats treated with high-level AGEs (advanced glycation end products) containing diet - Int J Impot Res 2021 Mar 12 - "To investigate, if advanced glycation end products (AGEs) are involved in erectile dysfunction (ED) and also ALT-711, a cross-link breaker of AGEs, has the therapeutic potential against the development of ED in rats treated with high concentrated AGEs including food ... To investigate, if advanced glycation end products (AGEs) are involved in erectile dysfunction (ED) and also ALT-711, a cross-link breaker of AGEs, has the therapeutic potential against the development of ED in rats treated with high concentrated AGEs including food" - Note:  I haven't come across any articles on ALT-711 in years.  It was big in the 90s.  I tried to buy some from a chemical company,  One of their reps called and asked me what I was going to do with it.  When I told him, he freaked out and wouldn't sell it.  There was a chemical recipe to make it posted on the internet.  I saved it but don't know where.  AGEs are a big area in anti-aging.
    • Alteon, Alagebrium, ALT-711 - fightaging.org - 9/24/06 - "ALT-711 was one of the most promising products for the same type of long-term, low-dose usage that seligilene (trade name Deprynl, a parkinsons medication with a 70 year history of medical use) and Metformin (a medication often given for Type II diabetes. Rather than working on insulin release, it works to maintain glucose tolerance, diabetes being a case of extreme glucose intolerance.)that became popular amongst anti-aging aficianados ... In the case of these two other meds, both the diseases they are used upon are among the groups that we all get eventually. Some of us die before we manifest symptoms, some of us manifest symptoms before we die. In either case, the oxidation of glial brain cells (parkinson's) and progressive glucose intolerance (diabetes) are inevitable. In both cases, these meds, formerly used for treatment, have proven useful as prophylactics against the diseases. They are both off-patent, and available inexpensively. Good ... In the case of ALT-711, the chemical compound had been discovered many years ago, and had traveled a circuitous route through academia, research firms, and finally, Alteon. There are two prominent attributes to Alagebrium (as Alteon renamed it). The first is that it is not a difficult compound to sysnthesize. An active black market rose very quickly after the early Phase I and II tests came in. Independent, lab-tested, certified for purity product was available for a short time on the grey market at about $3 per gram."
  • Effect of advanced glycation end-products (AGE) lowering drug ALT-711 on biochemical, vascular, and bone parameters in a rat model of CKD-MBD - J Bone Miner Res. 2019 Nov 19 - "In summary, treatment of CKD-MBD with an AGE breaker ALT-711, decreased FGF23, reduced aorta calcification, and reduced total bone AGE without improvement of bone mechanics. These results suggest little effect of ALT-711 on collagen, but potential cellular effects. The data also highlights the need to better measure specific types of AGE proteins at the tissue level in order to fully elucidate the impact of AGEs on CKD-MBD" - Note: Alt-711 was all the rage in the ‘90’s. I tried to buy some from a chemical company, and they said I was crazy. I found a way to make it on the internet, but I don’t trust myself.
  • Mediterranean Diet Supplemented With Coenzyme Q10 Modulates the Postprandial Metabolism of Advanced Glycation End Products in Elderly Men and Women - J Gerontol A Biol Sci Med Sci. 2016 Oct 21 - "Med diet modulated redox-state parameters, reducing AGEs levels and increasing AGER1 and GloxI mRNA levels compared with the SFA diet. This benefit was accentuated by adding CoQ, in particular, in the postprandial state. Because elevated oxidative stress/inflammation and AGEs are associated with clinical disease in aging, the enhanced protection of a Med diet supplemented with CoQ should be assessed in a larger clinical trial in which clinical conditions in aging are measured" - See ubiquinol products at Amazon.com.
  • Sulforaphane reduces advanced glycation end products (AGEs)-induced inflammation in endothelial cells and rat aorta - Nutr Metab Cardiovasc Dis. 2016 Apr 21 - "The present study demonstrated for the first time that sulforaphane could inhibit inflammation in AGEs-exposed HUVECs and AGEs-infused rat aorta partly by suppressing RAGE expression through its anti-oxidative properties. Inhibition of the AGEs-RAGE axis by sulforaphane might be a novel therapeutic target for vascular injury in diabetes" - See sulforaphane at Amazon.com.
  • Diet low in advanced glycation end products increases insulin sensitivity in healthy overweight individuals: a double-blind, randomized, crossover trial - Am J Clin Nutr. 2016 Mar 30 - "A diet that is low in AGEs may reduce the risk of type 2 diabetes by increasing insulin sensitivity. Hence, a restriction in dietary AGE content may be an effective strategy to decrease diabetes and cardiovascular disease risks in overweight individuals"
  • Atorvastatin prevents advanced glycation end products (AGEs)-induced cardiac fibrosis via activating peroxisome proliferator-activated receptor gamma (PPAR-γ) - Metabolism. 2016 Apr;65(4):441-53 - "Compared with the control group, in vivo treatment with Ator significantly retarded the AGEs-induced diastolic function and attenuated cardiac fibrosis, α-SMA, and RAGE over expression induced by AGEs ... In this study, we demonstrated that AGEs-induced fibroblast proliferation and differentiation were dependent on AGEs-RAGE-ERK1/2 pathway and that atorvastatin could block this pathway via activating PPAR-γ"
  • Dietary consumption of advanced glycation end products and risk of metabolic syndrome - Int J Food Sci Nutr. 2016 Feb 5:1-7 - "Subjects in the highest (>10 506 kU/d) compared to the lowest (<6673 kU/d) quartile category of AGEs had higher risk of abdominal obesity (OR: 1.19, 95% CI: 1.01-1.39) and hypertriglyceridemia (OR: 1.26, 95% CI: 1.07-1.49). Therefore, recommendation on restriction of AGEs intake could be a practical approach to prevent metabolic abnormalities"
  • Sugar Sag: Glycation and the Role of Diet in Aging Skin - Medscape, 12/23/15 - "First described in the context of diabetes, advanced glycation end products (AGEs) are formed through a type of non-enzymatic reaction called glycation. Increased accumulation of AGEs in human tissue has now been associated with end stage renal disease, chronic obstructive pulmonary disease, and, recently, skin aging. Characteristic findings of aging skin, including decreased resistance to mechanical stress, impaired wound healing, and distorted dermal vasculature, can be in part attributable to glycation. Multiple factors mediate cutaneous senescence, and these factors are generally characterized as endogenous (e.g., telomere shortening) or exogenous (e.g., ultraviolet radiation exposure). Interestingly, AGEs exert their pathophysiological effects from both endogenous and exogenous routes. The former entails the consumption of sugar in the diet, which then covalently binds an electron from a donor molecule to form an AGE. The latter process mostly refers to the formation of AGEs through cooking. Recent studies have revealed that certain methods of food preparation (i.e., grilling, frying, and roasting) produce much higher levels of AGEs than water-based cooking methods such as boiling and steaming"
  • New Antiglycative Compounds from Cumin (Cuminum cyminum) Spice - J Agric Food Chem. 2015 Nov 7 - "At equivalent concentrations, several of the isolates, including cuminoids C-E, were more potent inhibitors than the positive control, aminoguanidine, a synthetic antiglycative agent (>50 vs. 35%, respectively)" - See aminoguanidine at IAS.  See curcumin products at Amazon.com.
  • Carnosic acid as a major bioactive component in rosemary extract ameliorates high-fat diet-induced obesity and metabolic syndrome in mice - J Agric Food Chem. 2015 Apr 30 - "The mice were given a low-fat diet, a high-fat diet or a high-fat diet supplemented with either 0.14% or 0.28% (w/w) CA-enriched RE (containing 80% CA, RE#1L and RE#1H), or 0.5% (w/w) RE (containing 45% CA, RE#2), for a period of 16 weeks ... The dietary RE supplementation significantly reduced body weight gain, percent of fat, plasma ALT, AST, glucose, insulin levels, liver weight, liver triglyceride and free fatty acid levels compared with the mice fed with HF diet without RE treatment. RE administration also decreased the levels of plasma and liver malondialdehyde, advanced glycation end products (AGEs) and the liver expression of receptor for AGE (RAGE) compared with mice of HF group" - See rosemary extract at Amazon.com.
  • Quercetin Inhibits Advanced Glycation End Product Formation by Trapping Methylglyoxal and Glyoxal - J Agric Food Chem. 2014 Nov 20 - "We also revealed that in the bovine serum albumin (BSA)-MGO/GO system, quercetin traps MGO and GO directly then significantly inhibit the formation of AGEs" - See quercetin at Amazon.com.
  • New study postulates the role of dietary advanced glycation end products in the risk of Alzheimer's disease - Science Daily, 2/3/15 - "meat made the highest contribution of AGEs, followed by vegetable oils, cheese, and fish. Foods such as cereals/grains, eggs, fruit, legumes, milk, nuts, starchy roots, and vegetables generally make low contributions to the total amount of AGEs in a diet, either because they are generally prepared at low temperatures or since they comprise smaller portions of diets ... This epidemiological study supports our previous findings in animals and humans of an important role for dietary AGEs in Alzheimer's disease. We found that mice kept on a diet high in AGEs, similar to Western diet, had high levels of AGEs in their brains together with deposits of amyloid-β, a component of the plaques characteristic of Alzheimer's disease, while at the same time developed declines in cognitive and motor abilities. The mice fed a low AGE diet remained free of these conditions. In addition, clinical studies have shown that subjects with higher blood AGE levels, in turn resulting from high AGE diets, are more likely to develop cognitive decline on follow up"
  • Effect of Dietary Prebiotic Supplementation in Pre-diabetes - Medscape, 10/1/14 - "Thirty adults with pre-diabetes (Impaired Glucose Tolerance or Impaired Fasting Glucose) aged between 40–60 years will be randomly assigned to receive either 10 grams of prebiotic (inulin/oligofructose) daily or 10 grams placebo (maltodextrin) daily for 12 weeks ... Supplementation of the diet with bifidogenic prebiotic fibres (such as inulin) may reduce or retard the accumulation of AGEs in individuals at risk of developing type 2 diabetes. Prebiotics have been shown to improve and restore optimal microbial balance within the gastrointestinal tract, potentially reducing AGE absorption and/or production by the human host. Preliminary investigations indicate that consuming a high-AGE diet is sufficient to favour the proliferation of potentially pathogenic colonic bacteria over more beneficial species. Consumption of glycated proteins,[34] fried meats[61] and toasted wheat flakes[62] encouraged the preferential growth of greater numbers of detrimental gram negative and sulphate-reducing colonic micro-organisms when compared to control diets. Short Chain Fatty Acids (SCFAs) produced as a bacterial by-product of prebiotic fermentation act to lower the intestinal pH, inhibiting the growth of protein-degrading micro-organisms capable of producing potentially toxic metabolites. SCFAs also stimulate colonic smooth muscle contractions, speeding intestinal transit and limiting the time available for protein fermentation and putrefaction to occur in the gut.[63] Therapeutic manipulation of the gut microbiota with prebiotics may restore gut normobiosis and reduce AGE accumulation in humans at risk for type 2 diabetes development by the following mechanisms" - See prebiotic supplements at Amazon.com.
  • Dietary advanced glycation end products are associated with decline in memory in young elderly - Mech Ageing Dev. 2014 Jul 15 - "We here provide for the first time evidence in which high levels of dietary AGE (dAGE) are associated with faster rate of decline in memory in 49 initially non-demented young elderly (p=0.012 in mixed regression models adjusting for sociodemographic and cardiovascular factors). Since modifying the levels of AGEs in the diet may be relatively easy, these preliminary results suggest a simple strategy to diminish cognitive compromise in the elderly and warrant further investigation"
  • Life-long endurance running is associated with reduced glycation and mechanical stress in connective tissue - Age (Dordr). 2014 Aug;36(4):9665 - "Life-long regular endurance runners (master athletes) had a 21 % lower AGE cross-link density compared to old untrained. Furthermore, both master athletes and young athletes displayed a thicker patellar tendon. These cross-sectional data suggest that life-long regular endurance running can partly counteract the aging process in connective tissue by reducing age-related accumulation of AGEs. This may not only benefit skin and tendon but also other long-lived protein tissues in the body. Furthermore, it appears that endurance running yields tendon tissue hypertrophy that may serve to lower the stress on the tendon and thereby reduce the risk of injury" - 21% of 60 years would equate to 12.6 years younger.
  • Effects of Chebulic Acid on Advanced Glycation Endproducts-induced Collagen Cross-links - Biol Pharm Bull. 2014 Apr 24 - "We report the antiglycating activity of chebulic acid (CA), isolated from Terminalia chebula on breaking the cross-links of proteins induced by AGEs and inhibiting the formation of AGEs. Aminoguanidine (AG) reduced 50% of glycated BSA with glycolaldehyde (glycol-BSA)-induced cross-links of collagen at a concentration of 67.8 ± 2.5 mM, the level of CA required for exerting a similar antiglycating activity was 38.8 ± 0.5 mM. Also, the breaking activity on collagen cross-links induced by glycol-BSA was potent with CA (IC50 = 1.46 ± 0.05 mM), exhibiting 50-fold stronger breaking activity than with ALT-711, a well-known cross-link breaker (IC50 = 72.2 ± 2.4 mM) ... The chelating activities of CA, AG and ALT711 on copper-catalyzed oxidation of AA were compared, and in increasing order, ALT-711(IC50 of 1.92 ±0.20 mM) <CA (IC50 of 0.96 ± 0.07 mM ) <AG (0.47 ±0.05 mM)" - See chebulic acid at Amazon.com and aminoguanidine at IAS.
  • Chemicals in 'Western' Diet Show Alzheimer's-Like Effects in Mice - WebMD, 2/24/14 - "when they added the compounds -- called advanced glycation end products (AGEs) -- to the lifelong diets of laboratory mice, the animals developed greater amounts of beta-amyloid in the brain. Beta-amyloid is the protein that makes up the brain "plaques" seen in people with Alzheimer's disease ... mice fed these compounds developed more problems with movement and memory as they aged compared to mice that spent their lives dining on chow that produced low levels of these chemicals ... AGEs are naturally present in small amounts in the human body ... But you also ingest the compounds through food -- particularly animal products prepared at a high heat ... That includes fried, grilled or broiled meats, and dairy products that are pasteurized or sterilized"
  • Consumption of a Diet Low in Advanced Glycation Endproducts for 4 weeks Improves Insulin Sensitivity in Overweight Women - Diabetes Care. 2013 Aug 19 - "High heat cooking of food induces formation of advanced glycation endproducts (AGEs), which are thought to impair glucose metabolism in type 2 diabetic patients. High intake of fructose might additionally affect endogenous formation of AGEs ... Diets with high AGE content may increase development of insulin resistance. AGEs can be reduced by modulation of cooking methods but is unaffected by moderate fructose intake"
  • Vitamin D reduces deposition of advanced glycation end-products in the aortic wall and systemic oxidative stress in diabetic rats - Diabetes Res Clin Pract. 2013 Mar 20 - "Vitamin D may have an important role in reducing the risk of cardiovascular disease. Advanced glycation end-products (AGEs) such as Ne-(carboxymethyl)lysine (CML), have been implicated in diabetic vascular complications via oxidative stress-mediated pathways ... Untreated diabetes was associated with significantly elevated CML levels in the aortic wall (19.5+/-3.3 vs 10.2+/-4.7ng/mL), increased liver OSI (6.8+/-1.9 vs 3.1+/-0.7), and reduced serum TAC (0.4+/-0.1 vs 0.8+/-0.3mmol Trolox/L), in comparison with the control group. Cholecalciferol significantly blocked the accumulation of CML in the aortic wall (10.4+/-8.4 vs 19.5+/-3.3ng/mL), decreased liver OSI (4.2+/-1.4 vs 6.8+/-1.9), and improved serum TAC (1.0+/-0.2 vs 0.4+/-0.1mmol Trolox/L), compared with the untreated diabetic group" - See vitamin D at Amazon.com.
  • Arterial Stiffness and Wave Reflections in Relation to Plasma Advanced Glycation End Products in a Chinese Population - Am J Hypertens. 2013 Feb 28 - "AGEs accumulate with aging and high cholesterol and are associated with arterial wave reflections and, in an age-dependent manner, with arterial stiffness"
  • Eating deep-fried food linked to increased risk of prostate cancer - Science Daily, 1/28/13 - "men who reported eating French fries, fried chicken, fried fish and/or doughnuts at least once a week were at an increased risk of prostate cancer as compared to men who said they ate such foods less than once a month ... In particular, men who ate one or more of these foods at least weekly had an increased risk of prostate cancer that ranged from 30 to 37 percent. Weekly consumption of these foods was associated also with a slightly greater risk of more aggressive prostate cancer ... Deep frying may trigger formation of carcinogens in food ... Foods cooked with high heat also contain high levels of advanced glycation endproducts, or AGEs, which have been associated with chronic inflammation and oxidative stress. Deep-fried foods are among the highest in AGE content. A chicken breast deep fried for 20 minutes contains more than nine times the amount of AGEs as a chicken breast boiled for an hour, for example"
  • Crusty foods may worsen heart problems associated with diabetes - Science Daily, 10/22/12 - "We see evidence that cooking methods that create a crust -- think the edge of a brownie or the crispy borders of meats prepared at very high temperatures -- produce advanced glycation end products (AGEs). And AGEs are associated with plaque formation, the kind we see in cardiovascular disease ... people with higher rates of cardiovascular complications ate more of these glycated products. For each unit increase in AGEs intake, a study participant was 3.7 times more likely to have moderate to high risk for cardiovascular disease ... Boiling or stewing meat would reduce your AGEs intake further. And scrambling an egg with cooking spray instead of frying it leads to a significant reduction in AGEs"
  • Effects of metformin on markers of oxidative stress and antioxidant reserve in patients with newly diagnosed type 2 diabetes: A randomized clinical trial - Clin Nutr. 2012 Aug 21 - "Baseline values of the oxidative stress markers did not differ significantly between the two groups. In cases, after three months treatment, there was a significant reduction in AOPP [Advanced Oxidation Protein Products] (137.52 +/- 25.59, 118.45 +/- 38.42, p < 0.001), and AGE [advanced glycation end-products] (69.28 +/- 4.58, 64.31 +/- 8.64, p = 0.002) ... Use of metformin is more effective in reducing oxidative stress compared with lifestyle modification alone" - See metformin at The Antiaging Store.
  • Stop grilling dinner: Specific toxic byproduct of heat-processed food leads to increased body weight and diabetes, mouse study finds - Science Daily, 8/20/12 - "mice with sustained exposure to the compound, methyl-glyoxal (MG), developed significant abdominal weight gain, early insulin resistance, and type 2 diabetes. MG is a type of advanced glycation endproduct (AGEs), which is produced when food is cooked with dry heat. AGEs have been found to lower the body's protective mechanisms that control inflammation ... In the study, one group of mice was fed a diet high in MG over four generations, while the control group was fed a diet without MG ... Over four generations, the mice that ate the MG started to develop early insulin resistance and increased body fat, whereas the control group did not have either of these conditions. The researchers found that MG caused a marked deficiency in protective mechanisms, such as the survival factor SIRT1 that is present in fat and controls inflammation, while enhancing the metabolism of glucose and insulin. The ingestion of MG also adversely affected the activity of an important anti-AGE receptor called AGER1, which protects SIRT1 and fights insulin resistance ... clinical guidelines be revised to eliminate foods cooked using dry heat and replace them with methods that use lower heat or lots of moisture (water) as in stewing, poaching or steaming. Examples from the AGE-less diet include stewed beef, chicken and fish instead of grilled meats"
  • Therapeutic effect of combination of alagebrium (ALT-711) and sildenafil on erectile function in diabetic rats - Int J Impot Res. 2011 Dec 29
  • Fish intake, cooking practices, and risk of prostate cancer: results from a multi-ethnic case-control study - Cancer Causes Control. 2011 Dec 30 - "We observed that high white fish intake was associated with increased risk of advanced PCA among men who cooked with high-temperature methods (pan-frying, oven-broiling and grilling) until fish was well done (p (trend) = 0.001). No associations were found among men who cooked fish at low temperature and/or just until done"
  • AMD-like lesions delayed in mice fed lower glycemic index diet - Science Daily, 11/14/11 - "The dietary glycemic index (DGI) measures the rate at which glucose is delivered to the bloodstream after consuming carbohydrates. Higher GI foods including white bread and white potatoes trigger a rapid delivery of glucose that pushes the body to work overtime to absorb, whereas lower GI foods, like whole grain bread and fruits and vegetables, initiate a slower release of glucose that is more easily processed by cells ... Compared to the mice on the lower GI diet, mice on the higher GI diet demonstrated elevated accumulations of debris known as advanced glycation end products (AGEs) in the whole retina, particularly in the cells of the RPE. The RPE plays a crucial role in maintaining vision and its dysfunction results in the gradual central vision loss that is the hallmark of AMD. AGE accumulation has also been linked to tissue damage in other age-related diseases such as Type 2 diabetes and cardiovascular disease"
  • Inhibition of advanced glycation end-product formation on eye lens protein by rutin - Br J Nutr. 2011 Aug 25:1-9 - "Formation of advanced glycation end products (AGE) plays a key role in the several pathophysiologies associated with ageing and diabetes, such as arthritis, atherosclerosis, chronic renal insufficiency, Alzheimer's disease, nephropathy, neuropathy and cataract. This raises the possibility of inhibition of AGE formation as one of the approaches to prevent or arrest the progression of diabetic complications. Previously, we have reported that some common dietary sources such as fruits, vegetables, herbs and spices have the potential to inhibit AGE formation. Flavonoids are abundantly found in fruits, vegetables, herbs and spices, and rutin is one of the commonly found dietary flavonols. In the present study, we have demonstrated the antiglycating potential and mechanism of action of rutin using goat eye lens proteins as model proteins. Under in vitro conditions, rutin inhibited glycation as assessed by SDS-PAGE, AGE-fluorescence, boronate affinity chromatography and immunodetection of specific AGE. Further, we provided insight into the mechanism of inhibition of protein glycation that rutin not only scavenges free-radicals directly but also chelates the metal ions by forming complexes with them and thereby partly inhibiting post-Amadori formation. These findings indicate the potential of rutin to prevent and/or inhibit protein glycation and the prospects for controlling AGE-mediated diabetic pathological conditions in vivo" - See rutin at Amazon.com.
  • Restriction of Advanced Glycation End Products Improves Insulin Resistance in Human Type 2 Diabetes: Potential role of AGER1 and SIRT1 - Diabetes Care. 2011 Jul;34(7):1610-6 - "AGE restriction may preserve native defenses and insulin sensitivity by maintaining lower basal OS"
  • It's not an apple a day after all -- it's strawberries: Flavonoids could represent two-fisted assault on diabetes and nervous system disorders - Science Daily, 6/27/11 - "fisetin, a naturally-occurring flavonoid found most abundantly in strawberries and to a lesser extent in other fruits and vegetables, lessens complications of diabetes. Previously, the lab showed that fisetin promoted survival of neurons grown in culture and enhanced memory in healthy mice ... Mice fed a fisetin-enriched diet remained diabetic, but acute kidney enlargement-or hypertrophy-seen in untreated mice was reversed, and high urine protein levels, a sure sign of kidney disease, fell. Moreover, fisetin ingestion ameliorated anxiety-related behaviors seen in diabetic mice ... blood and brain levels of sugars affixed to proteins known as advanced glycation end-products-or AGEs-were reduced in fisetin-treated compared to untreated Akita mice. These decreases were accompanied by increased activity of the enzyme glyoxalase 1, which promotes removal of toxic AGE precursors ... substantial evidence implicates high blood AGE levels with many if not most diabetic complications ... excessively high AGE levels also correlate with inflammatory activity thought to promote some cancers. In fact, studies published by others confirm that fisetin decreases tumorigenicity of prostate cancer cells both in culture and in animal models ... humans would have to eat 37 strawberries a day ... Rather than through diet, Maher envisions that fisetin-like drugs could be taken as a supplement"
  • AGE Content of Foods - InHuman Experiment, 9/1/09
  • Serum advanced glycation end products is associated with insulin resistance - Diabetes Metab Res Rev. 2011 Feb 17 - "On multiple regression analysis, serum AGEs remained an independent determinant of HOAM-IR even after adjusting for age, gender, body mass index, waist, smoking, adiponectin and markers of oxidative stress and inflammation ... CONCLUSIONS: Formation and accumulation of AGEs progress during normal aging. We have demonstrated that circulating level of AGEs is associated with insulin resistance even in non-obese, non-diabetic subjects independent of adiponectin"
  • Inhibition of the receptor for advanced glycation endproducts (RAGE) protects pancreatic β-cells - Biochem Biophys Res Commun. 2010 Nov 24 - "Advanced glycation endproducts (AGEs) and the receptor for AGEs (RAGE) have been linked to the pathogenesis of diabetic complications, such as retinopathy, neuropathy, and nephropathy. AGEs may induce β-cell dysfunction and apoptosis, another complication of diabetes ... Inhibition of RAGE prevented AGE-induced pancreatic β-cell apoptosis, but could not restore the function of glucose stimulated insulin secretion (GSIS) in rat islets. In summary, the results of the present study demonstrate that AGEs are integrally involved in RAGE-mediated apoptosis and impaired GSIS dysfunction in pancreatic β-cells. Inhibition of RAGE can effectively protect β-cells against AGE-induced apoptosis, but can not reverse islet dysfunction in GSIS"
  • Sugar and Your Skin - ABC News, 11/30/10 - It's a video.
  • Nutrition and aging skin: sugar and glycation - Clin Dermatol. 2010 Jul-Aug;28(4):409-11 - "The effect of sugars on aging skin is governed by the simple act of covalently cross-linking two collagen fibers, which renders both of them incapable of easy repair. Glucose and fructose link the amino acids present in the collagen and elastin that support the dermis, producing advanced glycation end products or "AGEs." This process is accelerated in all body tissues when sugar is elevated and is further stimulated by ultraviolet light in the skin. The effect on vascular, renal, retinal, coronary, and cutaneous tissues is being defined, as are methods of reducing the glycation load through careful diet and use of supplements"
  • Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet - J Am Diet Assoc. 2010 Jun;110(6):911-916.e12 - "Modern diets are largely heat-processed and as a result contain high levels of advanced glycation end products (AGEs). Dietary advanced glycation end products (dAGEs) are known to contribute to increased oxidant stress and inflammation, which are linked to the recent epidemics of diabetes and cardiovascular disease ... Based on the findings, dry heat promotes new dAGE formation by >10- to 100-fold above the uncooked state across food categories. Animal-derived foods that are high in fat and protein are generally AGE-rich and prone to new AGE formation during cooking. In contrast, carbohydrate-rich foods such as vegetables, fruits, whole grains, and milk contain relatively few AGEs, even after cooking. The formation of new dAGEs during cooking was prevented by the AGE inhibitory compound aminoguanidine and significantly reduced by cooking with moist heat, using shorter cooking times, cooking at lower temperatures, and by use of acidic ingredients such as lemon juice or vinegar"
  • Metformin restores impaired HDL-mediated cholesterol efflux due to glycation - Atherosclerosis. 2009 Mar 19 - "In the presence of metformin or aminoguanidine (100mM), glycated HDL-mediated cholesterol efflux was restored to 97.5+/-4.3% and 96.9+/-3.1%, respectively"
  • Advanced glycation end products and diabetic foot disease - Diabetes Metab Res Rev. 2008 May-Jun;24 Suppl 1:S19-24 - "recent clinical studies have shown that the AGE-breakers may be able to decrease adverse vascular effects of glycation with few side effects"
  • Advanced glycation end products in senile diabetic and nondiabetic patients with cataract - J Diabetes Complications. 2008 May 26 - "The AGE distribution in the senile groups corroborates the hypothesis that the advanced glycation process might have a role in cataract formation, which in diabetic patients occurs vigorously as compared with nondiabetic cataract patients"
  • When It Comes To Living Longer, It's Better To Go Hungry Than Go Running, Mouse Study Suggests - Science Daily, 5/14/08 - "at least two studies which examined people who engage in high-volume exercise versus people who restricted their calorie intake, had a similar outcome: caloric restriction has physiological benefits that exercise alone does not ... One theory is that exercise places stress on the body, which can result in damage to the tissues and DNA. Another theory is that caloric restriction leads to physiological changes which benefit the body" - I still think it boils down to the ravages of higher insulin and blood sugar which increase advanced glycation end products a major cause of aging.
  • Telmisartan, an Angiotensin II Type 1 Receptor Blocker, Inhibits Advanced Glycation End-product (AGE)-elicited Hepatic Insulin Resistance via Peroxisome Proliferator-activated Receptor-gamma Activation - J Int Med Res. 2008 Mar-Apr;36(2):237-43 - "Candesartan, another ARB, did not affect AGEs-induced serine phosphorylation of IRS-1 at serine-307 residues in Hep3B cells. Our study suggests that telmisartan could improve AGE-elicited insulin resistance in Hep3B cells by inhibiting serine phosphorylation of IRS-1, at least in part, via activation of PPAR-gamma" - Note:  That might be another reason for considering telmisartan as a first line treatment for hypertension.  See telmisartan at OffshoreRx1.com.
  • Effect of Rosiglitazone on Cardiac Fibroblast Proliferation, Nitric Oxide Production and Connective Tissue Growth Factor Expression Induced by Advanced Glycation End-products - J Int Med Res. 2008 Mar-Apr;36(2):329-35 - "AGEs significantly accelerated proliferation, increased CTGF expression and decreased nitric oxide production in cardiac fibroblasts. These effects of AGEs were inhibited by RGZ in a dose-dependent manner"
  • Increased serum Advanced Glycation End products is a distinct finding in lean women with PCOS - Clin Endocrinol (Oxf). 2008 Mar 20 - "PCOS women exhibited statistically higher AGEs levels"
  • How Diabetes Drives Atherosclerosis - WebMD, 3/13/08 - "Abe's team showed that molecules called advanced glycation end products (AGEs), produced in greater levels by patients with diabetes, interfere with ERK5 cardioprotection. Glycation reactions cause the release of oxidizing side products like hydrogen peroxide (H202) that drive free radical production, inflammation and cell damage in many diseases" - I was always under the impression that it was advanced glycation end products in the first place.  I guess I was right before they discovered it.
  • DHEA Restores Oxidative Balance in Type 2 Diabetes - Medscape, 12/11/07 - "DHEA significantly reduced oxidative stress parameters in both plasma and peripheral blood mononuclear cells, the report indicates, and its administration was followed by a 50% decrease in levels of pentosidine (a marker of AGE formation)" - See DHEA at Amazon.com.
  • Face facts: Too much sugar causes wrinkles - MSNBC, 10/21/07 - "At blame is a natural process that's known as glycation, in which the sugar in your bloodstream attaches to proteins to form harmful new molecules called advanced glycation end products (or, appropriately, AGEs for short). The more sugar you eat, the more AGEs you develop. "As AGEs accumulate, they damage adjacent proteins in a domino-like fashion," ... Supplement your diet with at least 1 mg of vitamins B1 and B6 a day. These vitamins proved to be potent AGE inhibitors in a number of published studies"
  • Dehydroepiandrosterone administration counteracts oxidative imbalance and AGE formation in type 2 diabetic patients - Diabetes Care. 2007 Aug 17 - "Data indicate that DHEA treatment ameliorates the oxidative imbalance induced by hyperglycaemia, down-regulates the TNFalpha/TNFalpha receptors system and prevents AGE formation, suggesting a beneficial effect on the onset and/or progression of chronic complications in type 2 diabetic patients"
  • Telmisartan, an Angiotensin II Type 1 Receptor Blocker, Inhibits Advanced Glycation End-product (AGE)-induced Monocyte Chemoattractant Protein-1 Expression in Mesangial Cells Through Downregulation of Receptor for AGEs via Peroxisome Proliferator-activated Receptor-gamma Activation - J Int Med Res. 2007 Jul-Aug;35(4):482-9 - "Candesartan, an Ang II type 1 receptor blocker, did not suppress AGEs-induced superoxide generation. Telmisartan and the antioxidant, N-acetylcysteine, completely inhibited AGEs-induced MCP-1 overproduction by mesangial cells"
  • Protective Effect of (-)-Epigallocatechin Gallate against Advanced Glycation Endproducts-Induced Injury in Neuronal Cells - Biol Pharm Bull. 2007 Aug;30(8):1369-73 - "Advanced glycation endproducts (AGEs) are believed to be secondary factors in the selective neuronal injury associated with several neurodegenerative disorders. In this study, we investigated the protective effects of (-)-epigallocatechin gallate (EGCG), a major monomer of green tea polyphenols, against AGEs-induced damage in neuron cells. The results showed that EGCG treatment protected against glyceraldehyde-derived AGE-induced neurotoxicity" - See green tea extract at Amazon.com.
  • Thiazolidinedione increases serum soluble receptor for advanced glycation end-products in type 2 diabetes - Diabetologia. 2007 Jul 18 - "At 6 months, both rosiglitazone and sulfonylurea resulted in a significant reduction in HbA(1c), fasting glucose and AGE"
  • Cooking to Fight Inflammation? - Dr. Weil, 7/12/07 - "You can reduce your intake of AGEs by steaming or boiling foods or by making stews – the key is to cook at low heat and to maintain the water content of food"
  • Advanced glycation endproducts: what is their relevance to diabetic complications? - Diabetes Obes Metab. 2007 May;9(3):233-45 - "AGEs may potentiate the development of diabetic complications by activation of cell responses by AGE-modified proteins interacting with specific cell surface receptors, activation of cell responses by AGE free adducts, impairment of protein-protein and enzyme-substrate interactions by AGE residue formation, and increasing resistance to proteolysis of extracellular matrix proteins. The formation of AGEs is suppressed by intensive glycaemic control, and may in future be suppressed by thiamine and pyridoxamine supplementation, and several other pharmacological agents"
  • Advanced glycation end-products and arterial stiffness in hypertension - Am J Hypertens. 2007 Mar;20(3):242-7 - "Concentration of plasma AGEs is significantly higher in hypertensive than in normotensive subjects and related to aortic stiffness independent of age and blood pressure"
  • Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes - Diabetes Care. 2006 Sep;29(9):2064-71 - "Our study confirms micro- and macrovascular endothelial dysfunction accompanied by increased oxidative stress following a real-life, heat-processed, AGE-rich meal in individuals with type 2 diabetes and suggests benfotiamine as a potential treatment"
  • Effect of valsartan, an angiotensin II receptor blocker, on markers of oxidation and glycation in Japanese type 2 diabetic subjects: Blood pressure-independent effect of valsartan - Diabetes Res Clin Pract. 2006 May 29 - "low-dose valsartan treatment decreased serum AGEs level, whereas blood pressure level was unchanged. The effect of valsartan on AGEs might be a blood pressure-independent effect in type 2 diabetic subjects"
  • Antiglycation properties of aged garlic extract: possible role in prevention of diabetic complications - J Nutr. 2006 Mar;136(3):796S-9S - "S-Allylcysteine, a key component of aged garlic, is a potent antioxidant and can inhibit AGEP formation"
  • Phase II Data Show Alagebrium Reduces Arterial Stiffness in Elderly With Isolated Systolic Hypertension - Medscape, 11/23/05
  • Drug Compound Restores Youth To Aging Arterial Cells In Elderly Hypertensives, Hopkins Study Shows - Science Daily, 11/23/05 - "alagebrium, formally known as ALT-711 or 4,5-dimethyl-3-(2-oxo-2-phenylethyl)-thiazolium chloride, reduced stiffening in the vessel wall in the main artery of the neck (carotid artery) by as much as 37 percent. The drug also improved endothelial function, the ability of the vessels' inner lining to relax and dilate in response to increased stress from blood flow, by 102 percent"
  • Simvastatin's Benefits May Extend to Atherosclerotic Plaque Stabilisation in Diabetics - Doctor's Guide, 10/25/04 - "Simvastatin-dependent plaque stabilisation in patients with type 2 diabetes arises from the drug's ability to decrease expression of receptor for advanced glycation end products (RAGE), and thence to reduce metalloproteinase (MMP) activity, and promote plaque stabilisation"
  • New Class of Antihypertensive Agents Continues in Development - Medscape, 8/19/03 - "ALT-711 did not demonstrate statistical significance compared with placebo against the prespecified primary endpoint of reduction of SBP by office cuff pressure measurement at the highest of 4 dose levels (210 mg/day)"
  • Eating Food Cooked At High Temperature Accelerates Aging - Life Extension Magazine, 5/03 - "consuming foods high in glycotoxins might be responsible for the induction of a low-grade, but chronic state of inflammation. In addition, the glycotoxins in food cooked at high temperatures also promote the formation of glycotoxins in our living tissues. The implication of these findings is profound ... Inflammatory cytokine production can be suppressed with the proper supplementation of fish oil, DHEA, vitamin K and nettle leaf extract ... It is also important to avoid over consumption of foods high in arachidonic acid (beef, egg yolk, dairy, etc.) ... Consuming at least 1000 mg a day of carnosine, and/or 300 mg of the European drug aminoguanidine can inhibit pathological glycation reactions in the body" - See iHerb carnosine products.
  • Ramipril Reduces Advanced Glycation End Products In Non-Diabetic Nephropathy - Doctor's Guide, 4/21/03 - "Ramipril also mildly decreased levels of advanced glycation end products"
  • Vitamin C May Aid People with Diabetes - New Hope Natural Media, 2/13/03 - "Vitamin C inhibits all three of the biochemical reactions that are believed to contribute to the development of these complications: (1) the production of oxygen-derived free radicals, (2) the accumulation of sorbitol within cells, and (3) a tissue-damaging reaction called glycosylation" - [J. Hypertension/Medline]- See iHerb vitamin C products.
  • Preserving Clear Vision - Life Extension Magazine, 2/03 - "It is likely that glycation plays a role in aging in non-diabetics as well, especially those who eat diets high in sugars and refined carbohydrates or those who have blood sugars higher than normal but not high enough to merit a diabetes diagnosis ... Carnosine's best-known effect, however, is its ability to prevent the formation of advanced glycated end products (protein crosslinks). Carnosine competes with proteins for the binding sites they would occupy on sugar molecules, making it the best glycation preventative currently recognized in the world of nutrition research" - See iHerb carnosine products.
  • The Anti-Aging Effects of Carnosine - Life Extension Magazine, 1/03 - "Carnosine quenches the most destructive protein-oxidizing agent (the hydroxyl radical). One study showed carnosine was the only antioxidant to significantly protect cellular chromosomes from oxidative damage.2 Antioxidants cannot completely protect proteins. Nature's second line of defense is to repair or remove damaged proteins.3 This is where carnosine demonstrates its most profound anti-aging effect ... Studies show that carnosine is effective against cross-linking and the formation of advanced glycation end products (AGE).6,7 Glycated proteins produce 50-fold more free radicals than nonglycated proteins and carnosine may be the most effective anti-glycating agent known" - See iHerb carnosine products.
  • High-Heat Foods Could Be Bad For You - CBS News, 11/28/02 - "browned, crispy foods, like that Thanksgiving turkey you just ate, are loaded with proteins called AGEs which interact with sugar in the body to cause hardening of the arteries ... AGEs are deposited everywhere over time — in the kidneys, in the vessels of the eyes and they have been implicated in all of these major complications from diabetes"
  • Diabetic Heart Disease Risk Studied - Intelihealth, 11/12/02
  • Three Of 12 Patients Taking Pyridorin (Pyridoxamine Dihydrochloride) Convert From Macro- To Microalbuminuria - Doctor's Guide, 11/3/02 - "all dose levels of Pyridorin were well tolerated, with no serious adverse events reported and no discontinuations due to an adverse event ... Patients taking Pyridorin experienced an average decrease from baseline 24-hour urinary albumin excretion of 32 percent at day 45" - Sounds like Pyridorin by BioStratum is a competitor to pimagedine by Alteon.  Pyridorin and pimagedine are advanced glycation end product (AGE) inhibitors  Alteon is also working on ALT-711, which is an advanced glycation end product (AGE) reverser.  Carnosine and acetyl-l-carnitine are supplements believed to be advanced glycation end product (AGE) inhibitors. - Ben
  • Why Antioxidants Aren't Enough - Life Extension Magazine, 1/02
  • Oxidative Marker Found In Rheumatoid Arthritis Synovial Tissue - Doctor's Guide, 6/12/02 - "Raised AGE levels have been found in the serum and synovial fluid of patients with RA"
  • Glycation Levels Could Affect Progression Of Osteoarthritis - Doctor's Guide, 12/7/01
  • What constitutes a glycation-reduced diet? - Life Extension Magazine, 11/01 - "Glycation of proteins has been shown to play a prominent role in the development of many diseases related to diabetes, atherosclerosis and cataract formation. Glycation also occurs as a result of general aging. A glycation reduction diet would be one that is low in simple sugars and carbohydrates. There are also certain supplements that help reduce glycation, such as carnosine. Carnosine is the most effective natural anti-glycating agent ... Other supplements include alpha lipoic acid, chromium picolinate and calcium pyruvate"
  • Alteon's ALT-711 Found to 'Remodel' Cardiovascular System in Preclinical Study - Alteon, 9/24/01 - "released results of a new preclinical study that demonstrated the ability of ALT-711 to decrease the thickening of the heart that may occur as a result of hypertension, and to improve the function of the endothelium ... ALT-711 normalized left ventricular fibrosis, or the thickening of the left ventrical of the heart, and improved the function of the endothelium, the part of the cardiovascular system that regulates both the relaxation and contraction of blood vessels and contributes to the maintenance of the vascular structure. The authors suggest that ALT-711 may be effective for improving cardiovascular remodeling in hypertension"
  • AGE Breakers - Life Extension Magazine, 8/01 - "If ALT-711 is ever approved by the FDA, it will enable aging humans to reverse the effects of glycation, one of the most devastating consequences of aging"
  • Experimental Drug Decreases Age-Related Blood Vessel Stiffening - Doctor's Guide, 9/5/01 - "In a group of older people with vascular stiffening, the drug, ALT-711, significantly reduced arterial pulse pressure, defined as the difference between systolic blood pressure and diastolic blood pressure. It also improved the blood vessels' ability to stretch by about 14 percent"
  • Aminoguanidine: AGE Inhibitor - Phil Micans PharmB/IAS - "the membrane surface area of the rats was reduced by 30%. Furthermore, the collagen content of their arterial walls was increased by 24-30%. Aminoguanidine is therefore acting to improve overall heart and arterial condition and not just by preventing or slowing proteins from cross-linking, but also by decreasing the AGE-induced cross-linking of the extra-cellular matrix ... 11 patients with peripheral vascular disease were treated with aminoguanidine. Their blood vessels were so clogged that they couldn't walk for more than 500 yards. But after treatment with aminoguanadine the patients blood flow improved on average by 30% and the patients exercise abilities improved by 50% to 105%."
  • Alteon Initiates Phase IIb 'SAPPHIRE' Trial of ALT-711 in Systolic Hypertension - Alteon, 7/9/01 - "By "breaking" the pathological bonds that cause tissues, organs and vessels to stiffen and lose function over time, ALT-711 has demonstrated the ability to reverse certain age-related and diabetes-related conditions"
  • New Concepts Of Osteoarthritis Pathogenesis And Management Guidelines - Doctor's Guide, 6/14/01 - "With age, there is increased formation of advanced glycation end products (AGEs), which results in increased cross-linking of cartilage matrix and activation of cytokines"
  • Carnosine Nature's pluripotent life extension agent - Life Extension Magazine, 1/01 - "Carnosine distinctly improved the appearance of the aged mice, whose coat fullness and color remained much closer to that of young animals.  Significantly more carnosine-treated mice had glossy coats (44% vs. 5%), while significantly fewer had skin ulcers (14% vs. 36%) . . . .The sharpest contrast between the treated and untreated mice was seen in their behavior. Only 9% of the untreated mice displayed normal behavioral reactivity, compared to 58% of the carnosine treated mice."
  • Staying Young Forever, Putting new research findings into practice - Life Extension Foundation, 12/99 - "The formation of AGE happens in everyone and is a major factor in the aging process itself. These damaged proteins may lead to premature signs of aging (wrinkles and brown spots) and in the long run to damaging effects on most organ systems within the body . . . The amino acid carnosine is a natural AGE inhibitor found in high concentrations in the brain, muscle tissue and the lens of the human eye. It is also known to be an antioxidant capable of protecting cell membranes and other cell structures. In vitro studies demonstrated that carnosine inhibits glycosylation and crosslinking of proteins induced by reactive aldehydes, and that it is effective in reducing AGE formation by competing with proteins for binding with the sugars. The authors suggest that this nontoxic compound should be explored in the treatment of such conditions as diabetic complications, inflammatory disorders, alcoholic liver disease and possibly Alzheimer's disease."
  • Drug (ALT-711) Decreases Blood Vessel Stiffness in Older Primates - Medscape, 1/31/01 - "could be a new treatment for high blood pressure, heart failure, and certain vascular complications of diabetes. The treatment significantly decreased the stiffness of blood vessels"
  • Saving Yourself from AGE - Life Enhancement Magazine, 8/00
  • Arginine for Muscles, Memory, Sex and More - Life Enhancement Magazine, 12/99 - "Free arginine has been shown to help prevent a destructive process known as cross-linking, which is associated with accelerated aging. Excessive cross-linking reactions inevitably damage the kidneys, necessitating dialysis in advanced age"
  • Pimagedine Has Potential For Prevention Of Diabetic Complications - Doctor's Guide, 11/8/01
  • Lower AGE with Acetyl L-Carnitine - Life Enhancement Magazine, 8/99 - "Diabetics and others who become susceptible to high levels of glucose in blood serum as they age suffer from the formation of deleterious hybrid protein-sugar complexes known as advanced glycation end products (AGE) ... ALC decreased the glycation by 42%"
  • Business and Science Unite to Fight Aging - Life Extension Magazine, 10/98 - "One feature of aging and of diabetes is increased stiffness of blood vessels, such as the carotid artery in the neck. Egan showed that in rats, the distensibility of the carotid artery falls by more than 50 percent between 24 and 30 months of age in control animals, but falls by less than 7 percent in animals that received 50 mg/kg of Pimagedine in their drinking water. Further, over the same age interval, the rat heart-weight-to-body-weight ratio rose by about 50 percent in control animals, indicating heart failure; but the same ratio rose by less than about 7 percent in animals treated with Pimagedine. Pimagedine also normalized left ventricular stiffness and the amount of sugar attached to collagen (connective tissue protein). These are huge anti-aging effects. 

    But as good as Pimagedine is, ALT-711 may be a great deal better. ALT-711 is something called an "alpha dione cleaving agent." While Pimagedine prevents permanent glucose-protein crosslinks from forming, ALT-711 reverses glucose-protein crosslinks after they have formed. Still better, ALT-711 acts like an artificial enzyme, breaking crosslink after crosslink without itself being consumed in the reaction. It is as if ALT-711 were a "reverse free radical," setting up a chain reaction of positive, rather than negative, chemical reactions.""
  • Advanced Glycation End Products - DrMirkin.com - "cooking proteins with sugars in the absence of water/ forms advanced glycation products that can damage tissues in the body ... The frightening new news is that eating foods with these advanced glycation products raises blood and tissue levels and increases nerve damage"