Anti-AGEs Foundation

A.G.E.s & My Brain

Neurological Implications

A.G.E.s are found at high levels in the brains of people suffering from Alzheimer's, Huntington's and Parkinson's disease where they are thought to increase neuronal degeneration (1).

Neurological Research

RAGE is the receptor for advanced glycation end products. There is something called sRAGE (soluble RAGE) that can be measured in the blood. This marker can be used in predicting symptomatic vasospasm in a subarachnoid hemorrhage (bleeding of the brain).

RAGE is the receptor for advanced glycation end products and has several things that bind to it including advanced glycation end products, S100B and HMGB1. In individuals with ALS, these things that bind to the receptor itself (RAGE) are found at a much higher level in comparison to those who do not have ALS. Therefore, RAGE may be an important mediator in ALS.

A.G.E.s could potentially be the result of glycation of specific proteins related to Alzheimer’s disease. With glycation of these proteins it could lead to more severe neurotoxic effects.

The RAGE receptor binds A.G.E.s in foods we consume. This receptor is higher in patients with ALS. It's proposed that treatment with sRAGE (a competitor for AGE’s) is a potential treatment to help extend lifespan, decrease deficits, improve motor function and delay the onset of disease.

A.G.E.s found in the spinal cord of ALS patients suggests that late stage glycation is involved in the pathology of ALS.

A.G.E.s were found to be elevated in the cerebral spinal fluid of patients with ALS in comparison to patients without ALS.

A.G.E.s are found at higher levels in spinal cords of people with ALS.

There are multiple things that bind to the receptor for advanced glycation end-products. These are higher (both things binding and RAGE) in patients with ALS. A drug (FPS-ZM1) shows promising results on inhibiting these things from binding RAGE to have protective effects in those with ALS improving their lifestyle. These studies are in the beginning with mice trials with a lot more research to go. Read more

AGE-RAGE interactions trigger inflammation, oxidative stress, and cell death in many cells in our body. Therapeutic agents have been developed based on the focus of these interactions. Read more

This article summarizes the current research on the link between various neurodegenerative diseases like Alzheimer’s and Parkinson’s with AGEs. In general AGEs cause neurons to accumulate proteins and cause neuronal cell death. Read more

Mice fed a diet high in AGEs, which is seen in western diets which cook food at high temperatures, led to declines in memory and learning. The mechanisms studied in the study may help explain how Alzheimer’s develops. Read more

A review of the current literature on dietary AGEs and Alzheimer’s. In general, eating a diet low in AGEs has been linked with decreasing risk of Alzheimer’s. The Mediterranean and traditional Japanese diet have been shown to decrease Alzheimer’s risk, and the thought is because of low meat and dairy consumption. Read more

Sulforaphane, found in cruciferous vegetables like broccoli, has been shown to have inhibiting effects on neuroinflammation mediated by A.G.E.s. This could potentially be a good therapeutic candidate for neurodegenerative diseases such as Alzheimer’s.

Cruciferous vegetables such as broccoli, brussels sprouts, cabbage, etc. have a naturally occurring molecule that can help against Reactive Oxygen Species (ROS) and Advanced Glycation End Products (AGEs). These ROS and AGEs are bad for the cells and cause aging. Read more

Alzheimer’s involves the deposition of a protein known as amyloid in the brain. This protein can accumulate even faster in the presence of a high amount of AGEs in the body, causing Alzheimer disease to progress rapidly. Read more

A.G.E.s are involved in beta-amyloid plaque formation and degeneration of the CNS. However, serum A.G.E. levels are not an accurate tool for use in diagnosing Alzheimer's.

A certain type of AGE is associated with the accumulation of a protein that will contribute to the damage of neuron cells. α-tocopherol is a treatment that decreases the toxic effects of this AGE. Read more

A.G.E.s increase a process called oxidative stress, which is a known cause of Alzheimer's disease.

A mutation in a gene linked to Alzheimer’s disease has evidence of contributing to protein aggregation and AGE accumulation. Read more

Researchers found variances in certain types of AGEs between males and females with neurodegenerative disorders such as Alzheimer’s and Parkinson’s. The authors suggest that this should be considered when using AGEs to measure the pathology of these diseases. Read more

A study was done to see if there was an association between AGEs and patients who had both Alzheimer’s and Type 2 diabetes. Study showed AGEs helped predict cognitive decline for patients who had these 2 diseases together. Read more

This article goes over the various studies done that show type 2 diabetes may lead to an increased Alzheimer’s risk. Read more

This study examined about 3000 older individuals in terms of various diabetes related molecules and cognitive function. The more AGEs the worse cognitive function, however, higher glucagon levels seemed to have a protective effect. Read more

Dementia patients often develop paratonia, which is a form of muscle stiffness. A possible reason is because AGE accumulation seen in dementia patients leads to muscle damage which leads to muscle stiffening. Read more

Ribose was found to contribute to the formation of AGEs in the brain related to Parkinson’s. These particular AGEs were demonstrated to be even toxic to brain cells in vitro. Read more

There are several drugs, food extracts, vitamins, and other molecules that provide anti-oxidative effects which are likely to help protect against Parkinson’s disease. It is possible that these could provide treatment to Parkinson’s patients, but further research is needed. Several of these molecules likely work in similar damaging mechanisms as AGEs, so it is worth exploring. Read more

S100B is a neurotoxin that is linked to increasing the amount of AGE receptor (RAGE) in the area of the brain responsible for Parkinson’s. Targeting this neurotoxin may help diminish the affect of AGEs in the brain. Read more

Astrocytes likely play a role in protecting against the negative effects of RAGE in the brain by producing decoy RAGE receptors. Read more

A type of RNA can be used to prevent RAGE from being made. This treatment helped to prevent mice that were given Parkinson’s inducing drugs from developing symptoms and brain damage that would have normally occurred. Read more

A drug that is used for Parkinson’s disease, L-dopa, has been shown to increase oxidative stress and AGEs that leads to cellular damage. Administration of both Vitamin C and Rose Oil 1 hour before L-dopa showed a decrease in the amount of AGEs accumulated. Read more

People with schizophrenia have higher levels of A.G.E.s in their serum compared to other individuals.

This study gave an overview on studies about schizophrenia and AGEs. In the analysis, schizophrenic patients were shown to have lower vitamin B6 levels and higher AGE levels and also higher cardiovascular risk which is associated with higher AGE levels. Read more

There is a device that can detect A.G.E. accumulation in our bodies based on their fluorescence in our skin. A.G.E levels were higher in those with schizophrenia compared to those without schizophrenia using the skin fluorescence scanner.

Individuals with affective disorders such as depression have higher amounts of advanced glycation end products in their body.

AGEs are shown to be increased and can possibly be a predictor in premature death in affective disorders like major depressive disorder. Read more

Pyridoxamine (a vitamin) given with other treatments for schizophrenia can inhibit AGE formation and help reduce symptoms in schizophrenia patients.

Type 2 Diabetes is a condition that affects millions of Americans today. It has been noted that Type 2 Diabetes is also associated with neurodegeneration and brain atrophy. This study tried to find the relationship between the accumulation of Advanced Age Glycation Products and the association with the lower amounts of gray matter volume. Finding a relationship may be a pathway for more effective symptom management options. Read more

Skin autofluorescence, a way to measure AGE content, may put people with Type II Diabetes at higher risk of developing peripheral neuropathy. Read more

The natural compounds Ergothioneine and hispidin are antioxidants that are found in mushrooms. Researchers believe these compounds can be used to decrease the formation of AGEs in our body and even help prevent the development of diabetic encephalopathy in patients with Alzheimer’s. Read more

Patients with recent onset of psychosis have a higher accumulation rate of AGE, which is also associated with an increase in CVD risk. Read more

Lifestyle changes in high-risk populations could prevent AGE-attributed cognitive decline. This study shows effective recruitment strategies and successful subject adherence techniques for future studies on AGEs and cognitive function. Read more

Multiple sclerosis (MS) an autoimmune disease in which immune cells invade the central nervous system. It results in the formation of compounds known as α-dicarbonyls (such as methylglyoxal (MGO) and glyoxal (GO)), which in turn lead to the formation of advanced glycation end products (AGEs). Evidence suggests that MS patients have increased levels of AGEs compared to those who don’t have MS, and the increased presence of AGEs in MS patients also contributes to the severity of the disease. Read more

A study analyzed the brain samples of multiple sclerosis (MS) patients with brain samples who did not have MS and found MS patients had increased AGEs. Suggests in MS, AGEs play an inflammatory role in the disease. Read more

Increased CEL and AGE levels are seen in MS patients compared to healthy controls. CEL and AGE levels can be used as novel biomarkers. Read more

A pilot study was performed to see if there was a link between Multiple Sclerosis (MS) and a molecule called sRAGE. MS patients had lower amounts of sRAGE. sRAGE is thought to provide protection against Multiple Sclerosis. Female MS patients especially had lower amounts of sRAGE. More studies need to be done in this area to be conclusive since this was just a pilot study. Read more

This study showed a link between sRAGE and Multiple Sclerosis. Patients who were given medication for relieving Multiple Sclerosis symptoms, had increased levels of sRAGE, suggesting sRAGE is protective against Multiple Sclerosis. Read more

The study helped show esRAGE may have protective effects for multiple sclerosis patients and that some drugs can increase esRAGE levels. esRAGE is known to be made in the body and helps with regulating RAGE, which is the receptor for AGEs. Read more

The disease given to mice is very similar to multiple sclerosis in humans, so we can use these mice to understand multiple sclerosis better. The mice may not be as useful to test treatments for multiple sclerosis using what we know about AGEs. Read more

Mice subjected to MS showed increased AGE levels. The mice subjected to MS were unable to be treated with pyridoxamine, the typical MS treatment. Read more

The receptor for advanced glycation end-products is possibly implicated in the neurological symptoms in the parasitic infection of leishmaniasis. Read more

This study looked at microscopic sections of brain tissue and found that the receptor for AGEs were prominent throughout dead brain tissue in patients with viral meningoencephalitis. This suggests that AGEs play a role in the process of brain tissue destruction. Read more

A RAGE inhibitor was used to treat rats with meningitis and demonstrated prevention of behavioral and neurologic deficits. Read more

Small blood vessels in the brain deteriorate as aging occurs. This is associated with an accumulation in AGE related molecules. Read more

Epilepsy (seizures) is a progressive neurodegenerative disease where cognition is negatively impacted. Epileptic mice were created using experimental methods. It was shown that lacking TLR4 and RAGE caused less seizures to occur in these epileptic mice, which shows TLR4 and RAGE play a role in seizures. This can hopefully be applied to humans with seizures. Read more

A study was performed on epileptic patients from China who were either resistant to epileptic treatment or not resistant. It was discovered that certain Chinese patients who had a certain genetic variant were more likely to be resistant to epileptic treatment. More studies in larger and diverse populations need to be performed to confirm if this genetic variant is truly contributing to drug resistance in epileptic patients. Read more

This study found out that a molecule called sRAGE can be used as a marker for stroke severity. Generally speaking the lower the sRAGE levels, the more severe the stroke. Read more

A.G.E.s & My Eyes

Optical Implications

High A.G.E. levels in the eye is thought to change the structure and integrity of proteins within the cornea, retina, lens and optic nerves which eventually reduces the quality of our eyesight (2).

Optical Research

AGE content in cataracts was notably higher in patients with type 2 diabetes mellitus. A diet low in AGE-content foods may help delay cataract formation. Read more

Both Type 1 and Type 2 Diabetes are significant conditions that plague our society today. One of the complications of Diabetes, caused by tissue destruction of the Retina, is Diabetic Retinopathy. In this study, the measures of AGE levels in the humor of the eye, the blood, were studied and then statistically studied for finding the correlation. Since there was significant positive correlation, AGEs might be a target of cure for diabetic retinopathy. Read more

AGEs play a major role in the onset of diabetic neuropathies, which is a consequence of chronic hyperglycemia. Uncontrolled diabetes is dangerous because of these complications. AGEs accumulate in skin, lens, nerve myelin, etc. This study aimed to measure AGEs levels in lens via autofluorescence to see if it could be used in diagnosing diabetic peripheral neuropathies. Read more

A study was done on the results from a Scandinavian clinic that determined the relation of advanced end glycation products on type one diabetics and retinopathy. The study concluded that advanced end glycation products significantly increased the risk of diabetic retinopathy. Read more

A certain class of AGEs, AGE-2, could be involved in the onset of Vogt-Koyanagi-Harada (VKH) disease, which is an autoimmune disease of melanin-containing tissues, such as the eye, and its associated auditory system, meninges, and skin. There appears to be decreased AGE-2 levels in the body at the exacerbation stage of VKH, and an increase after recovery, suggesting AGE-2 might be involved in VKH onset. Read more

AGEs increase with aging and other genetic and environmental factors. AGEs contribute to degenerative diseases of the eye. Read more

Increased RAGE levels are seen in the optic nerves of patients with Alzheimer's disease. Increased RAGE may lead to optic neuropathy in AD patients. Read more

Diabetes is a condition that affects many people today. Earlier diagnosis of this disease may allow for significant changes to be made by allowing earlier access to resources, information and management. By using this screening tool and detecting the advanced age glycation products in a patient with diabetes, we can achieve our goal of managing the symptoms of someone who is diabetic. Read more

A.G.E.s & My Lungs

Respiratory Implications

A.G.E.s in the lung are thought to cause proteins to stick together leading to the development of asthma, chronic obstructive pulmonary disease and lung cancer (4).

Respiratory Research

RAGE is a receptor that is involved with inflammation processes in the body and is found in large quantities in the lungs. As a result, many studies have investigated the role that RAGE plays in different pulmonary diseases such as COPD, asthma, cystic fibrosis, and lung cancer. It was found that RAGE plays a role in these clinical outcomes and can be targeted to treat these conditions. Read more

RAGE is a receptor that is involved in the inflammatory pathway. Its expression in diseased vs. normal lung tissues was examined. It was found that RAGE is expressed more in diseased lungs. Based on this, RAGE can potentially be a useful therapeutic agent in the treatment of lung diseases. Read more

RAGE is the receptor for advanced glycation end products and is involved in inflammation processes in the body. Studies about the role of RAGEs in obstructive airway diseases were gathered and analyzed. It was determined that targeting the inflammation associated with RAGE could be useful in preventing the progression of obstructive airway diseases. Read more

An AGE-Reader scanner is able to measure the amount of AGEs in the skin at any given time. Researchers have found that individuals with chronic obstructive pulmonary disease (COPD) have higher levels of AGEs when scanned compared to individuals without COPD. Read more

sRAGE is a molecule in the body that has been shown to be deficient in patients with respiratory diseases such as asthma and COPD. This study supports the hypothesis that increasing levels of sRAGE could be used as a potential treatment option for these patients, yet more research has to be done before it can be used as a therapeutic strategy. Read more

sRAGE is a molecule in the body that could be a therapeutic agent in the treatment of acute lung injury and acute respiratory distress syndrome. Read more

This study found that RAGE is not a necessary component in the development of machine ventilator induced inflammation. The presence of soluble RAGE helped to limit the production of pro-inflammatory mediators in the ventilated, injured RAGE KO mice. This could be a potential therapeutic use of sRAGE. Read more

From food questionnaire studies there seems to be a link between the quality of one’s diet, including the amount of AGEs consumed, and their risk for developing obstructive airway diseases. The more that one’s diet is AGE-rich, the more likely they are to develop obstructive airway diseases such as COPD.

Drinking 5 or more non-diet soft drinks a week is correlated with an increased risk for developing chronic bronchitis which is a subset of COPD, in people aged 20-55 years old. Read more

Advanced Glycation End Products (AGEs) are compounds that can be found in foods that can cause inflammation in the body. These compounds are most commonly found in cooked red meats. This study examined the relationship between children consuming AGEs and the odds of wheezing. It was concluded that AGEs increase the odds of wheezing in children. Read more

Allowing children to drink many sugary drinks a week is now correlated with an increased risk of developing asthma in children ages 2-9 years old. Read more

Environmental pollutants and cigarette smoke has been tied to different chronic airways diseases such as COPD. More research has to be done on the mechanisms behind this and the other aspects of the molecule that is involved in this process. Read more

Cigarette smoke has been found to increase rates of atherosclerotic vascular disease and cancer in smokers due to the glycotoxins found in cigarette smoke. Read more

Advanced glycation end products can be measured in the lung and are a type of marker for overall lung health. When researchers fed rat groups diets that were high in AGEs, it was found that the amount of AGEs in their lung tissue increased. It was also observed that there was decreased levels of high mobility group box protein 1 (HMBG1), which is a marker for normal replication of cells. Decreased levels of HMBG1 could mean that the cells are not being as efficient as they could be.

The receptor for advanced glycation end-products (RAGE) plays a key role in wound healing of lung tissue. Stimulation of this receptor by two of its ligands, HMGB1 and AGEs, showed advanced healing capabilities. This could be due to the increased ability of these cells to migrate towards the injury and divide. Read more

Idiopathic pulmonary fibrosis (IPF) is the most common form of pulmonary fibrosis which causes scarring of the lungs that can lead to impaired lung function. There is no known cause for IPF, but researchers from this study have found evidence that increased levels of AGEs may play an important role. Researchers compared levels of AGEs in lung tissue of patients with different lung diseases and found that patients with IPF had significantly higher levels of AGEs. Read more

Pulmonary fibrosis is a pulmonary disease where chronic inflammation, increased cell populations, and abnormal deposition of collagen leads to lung damage and compromises pulmonary function. Idiopathic pulmonary fibrosis has no known cause, but AGEs appear to play some type of role in the disease. Increased levels of AGEs were found in the lung tissue of patients with clinically diagnosed pulmonary fibrosis, indicating that there may be a correlation between presence of disease and AGE levels. Read more

Advanced glycation end-products (AGEs) are found in inflammation processes in the body. Accumulation of AGEs in the body could be correlated with the aging process in the tissue in the lungs and could be preventing wound healing in the lungs. Read more

Idiopathic pulmonary fibrosis is a serious lung disease that is usually fatal within 4 years of the diagnosis. Advanced glycation end products (AGEs) and their receptors (sRAGE) have been shown to be involved in idiopathic pulmonary fibrosis. This study showed that the ratio between AGEs and sRAGE could be used to diagnose different lung diseases. Read more

This study compared a group of tuberculosis (TB) patients to a control group and found that the TB patients had higher levels of sRAGE (a protein receptor capable of binding to AGEs). While the exact mechanism is unclear, this study suggests that sRAGE levels could be correlated to tuberculosis and used as a measurement to gauge RAGE hyperactivity. Read more

RAGE is the receptor for advanced glycation end products that is present in the lungs. The role of RAGE in developing pulmonary emphysema was studied and it was concluded that it could be a therapeutic target for preventing this disease. Read more

An experiment was performed in which mice with and without RAGE receptors were exposed to allergens and subsequent testing was done to examine their lungs, specifically for any evidence of asthma symptoms. It was found that mice without RAGE receptors were found to have no asthmatic response to allergens. This implies that there is some connection between RAGE and developing asthma symptoms. Read more

Blood and sputum levels of many different parts of the RAGE system were examined in patients with cystic fibrosis, diabetes, cystic fibrosis with associated diabetes, and healthy individuals. The data obtained found that there is a protective nature of the free floating RAGE receptors, and a connection between membrane bound RAGE receptor and RAGE ligands to a diseased state. The cystic fibrosis patients with associated diabetes showed the largest ratio of membrane RAGE to free floating RAGE suggesting they have a large amount of inflammatory RAGE and a lower relative amount of protective RAGE. Read more

This study examined the role of the RAGE receptor in the chronic lung inflammation that accompanies M. tuberculosis infections. It was previously thought that RAGE enhanced the body's natural inflammatory response, but this study found that mice lacking the RAGE receptor actually demonstrated enhanced inflammatory responses compared to mice that possessed the RAGE receptor. This finding suggests that the RAGE receptor is important in preserving the balance between inflammatory benefit and harm during the immune response to M. tuberculosis infection. Read more

Advanced glycation end products (AGEs) have been found to increase with aging and play a role in inflammatory processes in the body. Accumulation of AGEs has been shown to negatively affect lung function. Preventing this accumulation could help to prevent lung pathologies. Read more

The skin autofluorescence reader (AFR) can be used on individuals to examine the amount of overall AGEs in their body due to the structure of the AGEs. A study was performed examining the blood levels of AGEs, specifically CML, CEL, and pentosidine, and AFR levels of individuals with COPD compared to individuals without. It was found that CML was lower, CEL was higher, pentosidine was no different, and AFR was higher, in COPD patients compared to the control group. Read more

Aspiration-related acute lung injury is a common cause of death related to anesthesia. Advanced glycation end products (AGEs) play a role in inflammation in the body. This study showed that a diet rich in AGEs leads to high levels of AGEs in the blood which can contribute to lung inflammation in patients after gastric aspiration. Thus, this shows that restricting high AGEs food consumption after lung injury could be beneficial for preventing further complications. Read more

Pulmonary hypertension is high blood pressure of the arteries in the lungs and heart. It is a rare, but fatal disease that has slowly been increasing over the past five years. Evidence from scientific studies may suggest that increased interaction between AGEs and their receptor RAGE in the lungs may contribute to pulmonary hypertension. They do so by making the arteries less stretchy and more resistant to blood flow. Read more

In studies of mouse lung tissue, it appears that the older one is, the more AGEs there are that accumulate in the lungs. This has the ability to affect lung function in a negative way and may contribute to chronic lung diseases. Read more

This study looked at the amount of AGEs and RAGE in the lung tissue of people with chronic obstructive pulmonary disease (COPD) and those without. The results showed that the COPD group had a higher intensity of both AGEs and RAGE in their lung tissue. This, in combination with the known functions of AGEs and RAGE, suggests that these two compounds could participate in the development of COPD. Read more

Cystic fibrosis patients can develop diabetes associated with their lung disorder, which seems to further deteriorate their lung function. This study was examining if these patients with cystic fibrosis-related diabetes had higher levels of AGEs and RAGE than cystic fibrosis patients or control patients. RAGE levels between the groups were not different, but AGE levels were significantly higher in the cystic fibrosis-related diabetes group. This suggests that increased AGE levels could be correlated to poorer lung function in these patients. As always, more work must be done to understand these AGE-lung function relationships. Read more

Cells infected with M. tuberculosis produce elevated levels of Methylglyoxal (MG) and AGEs. Methylglyoxal (MG) and AGEs work together within these cells to induce apoptosis, or cell death. This increased cell death could contribute to the formation of granulomatous lesions observed in TB patients. Read more

The receptor for advanced glycation end products (RAGE) was found to be necessary in producing both chronic and acute allergic responses in the lungs. This finding suggests that RAGE manipulation could serve as a potential new treatment avenue for asthma sufferers. Read more

A.G.E.s & My Heart

Cardiovascular Implications

High levels of A.G.E.s in the circulation is associated with increased risk of cardiovascular disease. A.G.E.s are thought to stick to the walls of blood vessels leading to their blockage and increased risk of heart attack (5).

Advanced glycation end products (AGEs) are metabolic byproducts that can interfere with our body’s cellular processes. More specifically, AGES are believed to be involved in the development and severity of several cardiovascular diseases, such as heart failure (HF). Therefore, it is possible that therapeutic treatments that reduce blood levels of AGEs may be helpful in treating patients with cardiovascular diseases.

Advanced glycation end-products (AGEs) are harmful molecules that are formed during reactions with sugars and protein. When these molecules accumulate in the body, they can negatively impact one’s health and previous research has suggested that elevated AGE levels may even be involved in cardiovascular disease. In this study, the literature reviewed collectively supports a correlation between AGE levels and the development of heart failure. Although additional research will be needed to fully understand the role of AGEs in humans, the evidence explored in this study suggests that interventions designed to lower AGE levels may result in promising outcomes for individuals with heart disease. Read more

Medications that decrease blood levels of advanced glycosylation end products (AGEs) and/or increase levels of the soluble AGE receptor (sRAGE) may be beneficial in treating individuals with stiff arteries, like those with hypertension.

In individuals with diabetes, high blood levels of AGEs may result in coronary artery damage (and coronary artery disease) even in the absence of pre-existing arterial stiffness.

Isoproterenol is a synthetic catecholamine that can damage the heart muscle and cause acute myocardial infarction. Using isoproterenol to induce damage to heart muscle, advanced glycation end products (AGEs) can be used to assess the extent of damage. This can aid earlier diagnosis and prognosis.

Advanced glycation end products and advanced oxidation protein products are two very useful markers in studying patients suspected of cardiovascular events. Because these markers, as well as, others such as cholesterol, LDL, triglycerides, and HDL can explain the progression of cardiovascular events, it is important to note that certain levels are required in order to stay healthy. Any increases or decreases in specific levels can exacerbate the disease and pose a greater risk of negative outcomes.

Diet, especially the fat content of the diet, plays a significant part in the amount of AGEs a person is exposed to and the subsequent development of cardiac disease. Mice that are fed a high fat diet and have normal functioning AGE receptors are particularly susceptible to developing various symptoms of cardiac disease as compared to mice that are fed a normal diet and have reduced expression of these receptors. Read more

Consumption of low carbohydrate and fat meals that have high AGE levels has negative short-term effects on the cardiovascular system in both diabetic and non-diabetic patients. The results of this study could demonstrate important implications for the development of chronic heart disease through the accumulatory effect of frequent short-lived insults. Read more

The drug ALT-711 has proven to be effective in reducing stiffness in the left ventricle that is caused by AGE cross-links due to aging. The study recruited 18 dogs spread over 3 groups, examining them over a period of 4 weeks. Read more

48 nondiabetic patients with CAD were followed and stenosis was tested via coronary angiograms. The results of the study determined a relationship between AGEs in blood plasma and the severity of CAD in patients without diabetes. Read more

This study looked at a nondiabetic Finnish population at two points in time, once in between 1982 and 1984 and about 18 years later in 2001. The follow-up sample looked at the living and non-living participants and looked for various health issues and risk factors that each participant exhibited. After culminating all this information, it looked to see if advanced glycation end products could predict total mortality, cardiovascular disease mortality or coronary heart disease in nondiabetic subjects. Some evidence was found that nondiabetic women with elevated serum AGE levels could be identified as an at-risk patient in a low-risk population. Read more

AGE levels are shown here to be elevated in Type II diabetic patients and may be associated with complications such as poor glycemic control, an indicator of diabetes management, and heart disease. Read more

A diet restricted in AGE may be effective in decreasing the risk of diabetes and cardiovascular disease in overweight individuals. Read more

AGEs have long been studied and been associated with cardiovascular disease and diabetes. A new protein called Rap1A can also be a therapeutic target to aid in the prevention of cardiac disease and also the complications of diabetes. Read more

Evidence suggests a correlation between children who have type I diabetes with reduced diastolic function and increased levels of methylglyoxal-derived hydroimidazolone-1 (MG-H1), which is a type of advanced glycation end product (AGE). There is also some possibility that higher BMI in this demographic could potentially correlate with a high level of AGEs in their blood serum. Read more

Exercise can help promote faster recovery from heart disease and help prevent new heart problems from occurring. Research has suggested that elevated levels of advanced glycation products (AGEs) may be associated with a decreased ability to exercise. Having higher levels of AGEs in your body may make recovering from heart disease more difficult because it can limit your ability to exercise. Read more

AGE soluble receptors (sRAGE) compete with AGE receptors (RAGE) by acting as ‘decoy receptors’ in the inflammatory pathway, thus reducing AGE-associated inflammation. This study suggests that there is an increase in sRAGE levels associated with physical activity, indicating that physical activity may play a role in reducing the inflammatory effects of AGEs, especially in cardiovascular disease. Read more

Type One Diabetics with elevated levels of advanced end glycation products had progressive thickening of the carotid arteries due to increased plaque formations. This happened despite an adjustment of the patient's A1C. This implies that AGE’s are mediating the crosslinking of the matrix in the coronary arteries. This shows a correlation of hyperglycemia as a risk factor for calcium deposition. Read more

Rheumatoid arthritis is associated with risks of cardiovascular disease due to chronic inflammation involved in RA. The chronic inflammation results in production of advanced glycation end products (AGEs), which are in turn correlated with cardiovascular events and the formation of atherosclerotic plaque, and reduction in elasticity of small arteries--especially in the presence of other AGE-promoting factors (i.e. smoking and diet). Read more

Improperly controlled diabetes leads to increased AGE and RAGE accumulation in aortic valves, which could result in aortic stenosis progression in people who have diabetes. Aortic stenosis is narrowing of the aortic valve, which restricts normal blood flow. Read more

Poor management of type 2 diabetic cardiomyopathy means the disease is progressing, involving AGE accumulation. This in turn could potentially increase certain fatty inflammatory factors which influence disease severity. Read more

People with diabetes have higher AGE accumulation compared to those who don’t. AGEs are involved in diabetic cardiovascular complications. Matrix metallopeptidase 9 (MMP-9) is an enzyme involved in tissue breakdown and remodeling. Both AGEs and MMP-9 levels are increased in diabetic patients, which demonstrates the risks of uncontrolled diabetes on cardiovascular health. Read more

For some background, a couple of the listed lab abbreviations will be explained. MMP-9 is a protein enzyme associated with collagen breakdown within the fibrous cap of atherosclerotic plaques. CRP is an independent predictor of systemic inflammation and AMI stands for Acute Myocardial Infarction. This study elucidated the increased risk of high CRP, MMP and sRAGE levels in accordance to Acute Myocardial infarction when compared to controls of similar health. Additionally, current smoking status was listed as a near-significant (significant based on their criteria) factor for development of AMI when compared to controls. What should be taken away from this article is a patient may be able to be screened for risk of AMI based on these three lab levels and their current history of smoking. Read more

It is important to reduce AGEs production in order to delay the onset of cardiovascular complications in newly diagnosed type 2 diabetes patients and to minimize cardiovascular risk in established T2DM patients. Read more

There are higher levels of AGEs associated with cardiovascular disease and type 1 diabetes, independent of other risk factors. AGEs may explain the increase in cardiovascular disease and mortality associated with type 1 diabetes. Read more

A potential Advanced Glycation End-product (AGE) breaker, C16, was investigated to determine it’s ability to treat the effects of AGE accumulation. AGE accumulation is associated with diabetes and can lead to cross-linking (similar to adding a support beam to make a structure more rigid) that has a detrimental effect on the function of an organ, in this study, the heart. The study found that when a diabetic rat was treated with this C16 “AGE-breaker” it was determined through multiple pathways (measuring heart and arterial function along with the solubility of tail collagen) that C16 has a potential ability to restore function to the heart and increase tail collagen solubility. Read more

CML and CEL are Advanced Glycation End-Products (AGE’s) and in this study, the researchers looked to see if these two AGE’s can be used to identify clinical health problems. The researchers took blood samples at the beginning of the study and some time later. After following patients over the course of their Chronic Heart Failure they looked to see if the AGE’s would predict any clinical problems. The study found that CML could but when considered against another lab value, GFR, its ability to predict was taken away. The researchers suggested that in the future further research should be done in this area to observe the parallels between kidney function, Chronic heart failure and AGE’s. Read more

This study shows that when DJ-1 is experimentally cut out from the genome, there are more adverse reactions that occur within the heart due to the inability to protect itself. This suggests that DJ-1 acts as a cytoprotective (cell protecting) protein against induced heart failure by reducing glycative stress. The results of the study suggest the possibility of utilizing a gene therapy to deliver an active form of DJ-1 to the heart to protect against the consequences of ischemic (low blood flow) injury. Read more

Advanced glycation end products accumulation in tissues can be measured by skin autofluorescence (SAF). A study was done with Type One Diabetics (followed for 7 years) to measure the amount SAF and how that was a potential indicator of major adverse cardiovascular events (MACE) in these patients. At the studies conclusion they found that SAF and MACE had a very significant correlation in these patients I.e. the higher the SAF value the more likely they were to have a MACE. Read more

A.G.E.s & My Skin

Dermal Implications

A.G.E. accumulation in the skin enhances wrinkling, loss of elasticity, stiffness, promotes accelerated aging, and increases risk of skin cancer (12).

People with psoriasis are more likely to have cardiovascular comorbidity due to the excessive production of advanced glycation end products (AGEs) which promote oxidative stress and inflammation. Increased levels of AGEs will alter the structure of the heart promoting premature atherosclerosis.

The skin is a barrier that helps protect us from various biological and physical threats but overtime cannot work as effectively. AGEs have a role in altering the skin properties and wound healing by weakening collagen.

Advanced glycation end products are known for recognizing the negative role in aging and chronic disease development. Skin autofluorescence is a common way in recognizing AGEs accumulation but research is limited with dark skinned people. This study identifies if SAF is a good way to recognize this accumulation and opens doors for more research in improving SAF.

Advanced glycation end products (AGEs) are fundamental in age-dependent changes. Increased ultraviolet exposure (sun-exposure) can amplify the accumulation of the glycation end products and contribute to the skin aging process.

Glycation is a process that interferes with skin repair and can be aggravated by diet as well as ultraviolet exposure. Preventative measures such as sunscreen are important in controlling glycation and need to be started earlier. Promoting dietary changes and skin products can help reduce inflammation and stress.

AGEs are important contributors in age related chronic diseases but can contribute as early as you are born. External sources of AGE such as formula and smoking can have a significant impact on infants AGE accumulation in addition to birth weight and type of delivery.

AGEs play a crucial role in oxidative stress but an elevated production can lead to cell damage and cell death. This stress is prominent in aging and age related diseases.

Skin autofluorescence is a well-known marker for advanced glycation end product accumulation. Secondhand smoking is associated with higher SAF levels and increased AGEs. Smoking cessation can be beneficial and help reduce external levels of AGEs.

Lip and facial skin can be harmed by glycation damage due to chronic stress. Gromwell (Lithospermum erythrorhizon) root has provided multiple skin benefits by controlling oxidative stress, inflammation, and UV absorptive properties.

Research has suggested oxidative stress is a huge factor of HPV-related issues such as warts. The imbalance of prooxidants and antioxidants is a key for these warts.

People with severe psoriasis are more likely to have other medical issues such as cardiovascular disease due to more advanced glycation end products. Advanced glycation end products (AGEs) are formed from within or from the environment and this study identifies what constant inflammation can lead to.

The accumulation of AGEs has a plethora of effects on skin aging and targets extracellular matrix proteins such as collagen. The aging of skin could potentially be slowed with vitamin/nutrient intake and dietary restrictions. Additionally, research exhibits that smoking and sun exposure have significant impacts on skin glycation that leads to skin aging. Read more

AGEs accumulation affects many characteristics of healthy skin. Skin aging often presents as loss of facial contour and decreased hydration, firmness, elasticity, and poor skin texture. With the use of a face cream containing carnosine, there can be significant improvements of skin aging signs. Read more

AGEs are found in excessive amounts in diabetic and aging individuals. These individuals cannot be classified by dry, normal or oily skin and need more products that maximize their skin appearance and performance.

Vitiligo is an autoimmune skin disease that is controlled by reactive oxidative species such as advanced glycation end products. Higher levels of AGEs are seen in those with vitiligo and with similar pathogenesis such as psoriasis and alopecia.

Research has shown that the accumulation of AGEs has a strong correlation to severe psoriasis. The products that form due to AGE accumulation cause inflammation within the body and induce a process of keratinocyte cell death, which is relevant to the development of psoriasis.

AGEs has been suggested to contribute to the development of various skin disorders and skin aging. Natural compounds and/or extracts are a good preventative measure to use in order to decelerate skin aging. The use of akebia quinata fruit extract (AQFE) could be used as a therapeutic agent as it possesses antioxidant and antiglycation activity thereby, producing an anti-wrinkle effect. Read more

Melanoma has been found to be correlated with an accumulation in AGEs in skin. AGEs can be synthesized and accumulated in skin due to UV radiation/exposure, which can cause melanoma cells to spread and/or grow. Read more

Foods high in sugar and certain cooking methods result in increased ingestion of AGEs, leading to accumulation in the skin. The accumulation of AGEs in the skin causes reduced functionality of vital skin components such as collagen, fibroblasts, and keratinocytes, which are responsible for skin health maintenance and wound healing. Read more

Studies show that a whole-food plant-based diet provides essential vitamins such as vitamin A, C, and E for maximal antioxidant function. These vitamins have been shown to lengthen telomeres, which prevents cellular damage to reduce skin aging. Read more

Peripheral neuropathy in diabetic patients is associated with higher levels of AGE in the skin. Read more

Complications involving the skin due to aging and diabetes can be reduced and managed using oral supplementation of carnosine/carcinine. This type of oral supplement has shown to improve overall skin appearance and a reduction of fine lines. Read more

Hallmarks of photoaging include skin pigmentation in conjunction with wrinkles. Studies show that exposure to UV irradiation promotes the formation of AGEs thus, inducing melanin production leading to skin pigmentation. Read more

High levels of AGE in the skin of diabetic patients with an increased HbA1c are not due to high blood sugar. Other reasons for elevated HbA1c are more likely causing higher AGE deposition. Read more

A study was done on Type One diabetes patients with a HbA1C of 9 (average) without any other chronic diseases. They looked at the levels of glycation end products contained in their skin with a DiagnOptics AGE Reader. The goal of this study was to determine if the T1D patients with elevated body fat or normal fat had an increase in glycation end products in the skin. The study concluded that the elevated body fat T1D group had a significantly higher level of AGE’s which contribute to development of diabetes complications. Read more

Lupus is correlated with advanced glycation end products, yet only some of the advanced glycation end products are correlated with the progression of this disease, which is why further research is necessary to determine their role in the pathogenesis of SLE. Read more

A.G.E.s & My Kidneys

Renal Implications

A.G.E.s in the kidney promote chronic kidney disease and are associated with kidney failure through increases in inflammation and oxidative stress (8).

Renal Research

The kidneys are the main organ that processes AGEs from the diet, and a place where AGEs can accumulate and cause problems. This study looked at the effects of dietary AGEs on kidney function in rats with renal insufficiency and found that a diet high in AGEs had damaging effects on kidney function, while a low-AGE diet showed some recovery of renal function over time.

This study suggests that higher AGE intake from fats has an impact on kidney disease progression. Read more

AGEs increase the production of angiotensinogen, which is found in the kidneys and linked to the development of diabetic nephropathy. These findings have led to a potential target for therapy in preventing or treating kidney injury in diabetes mellitus.

The relationship between advanced glycation end-products (AGEs) and diabetic and non-diabetic renal disease and aging continues to be studied thoroughly in order to seek out more specific treatments targeting AGEs aside from the antidiabetic and antioxidative treatments currently in use. Read more

AGE’s can cause an immune response in the kidney which can impact its function. Increased exposure to AGE’s has been shown to harm kidney health.

AGEs are formed in chronic diseases like Chronic Kidney Disease, and can contribute to the associated conditions like cardiovascular complications, though it is not known exactly how. There are several drugs in development to decrease AGE levels in the body, and there may be lifestyle changes that can help as well.

Several drugs are currently being investigated for their effects on reducing AGEs in the body. Some of these medications may be implicated in treatment of the complications of diabetes, including diabetic kidney disease. Read more

This studied examined the association of an accumulation of AGEs in patients with chronic kidney disease and age and gender-matched healthy subjects with endothelial dysfunction and the mechanism of how it works in those with chronic kidney disease. The study concluded that patients who had high measurements of AGE were found to suppress expression of certain enzymes that are necessary for proper function, emphasizing that AGEs may play a major role in progression of further disease. Read more

Premature aging in patients with chronic kidney disease (CKD) can be accelerated by AGEs, which can contribute to other health complications if not cleared by the kidneys. Strategies that target these areas can reduce the absorption of these AGEs, which can in turn help prevent premature aging in patients with CKD. Read more

Advanced glycation end products may be used to predict loss of kidney function in type II diabetics. They may also be related to a specific type of kidney lesion in diabetics with kidney disease. Read more

AGE’s can accumulate in your kidney and lead to kidney damage. Once this damage has occurred, the ability to get rid of AGE’s from the blood is significantly impacted. This decrease in AGE’s metabolism may lead to further health deficits. Read more

A study was done to determine the role of advanced end glycation products in nephropathy in type 2 diabetic patients. They took the results over a two-year period. The study found the level of low molecular weight advanced end glycation products were elevated in type 2 diabetic patients with impaired renal function. This suggests a correlation between nephropathy and the level of advanced end glycation products. Read more

A study was done to determine the effects of advanced end glycation products on diabetes and diabetic complications in addition to the removal of advanced end glycation product removal by lysozymes. This study found that lysozymes facilitated the removal of advanced end glycation production as well as protecting diabetics against renal damage. Read more

This study found that in people who suffer from both Type 1 and Type 2 Diabetes, there has been a link found between the protein found in the urine and also the AGE found in the urine. This can potentially be used as a factor to aid in the diagnosis of having both forms of diabetes and can be used as a non-invasive option. This can provide earlier access to resources for people who need them. Read more

The blockage of MMP7 is decreased which is a step in the degradation of the matrix when it comes to progressive renal disease. Read more

AGEs have been shown to be involved in the development of diabetic nephropathy, which is one of the main causes of chronic renal failure. Rosiglitzaone is a drug that activates a receptor, which decreases the amount of a protein that is partially responsible for diabetic nephropathy. Thus, this drug may help prevent nephropathy from occurring, despite the presence of AGEs in the body. Read more

AGEs are a product that our body forms when we eat different types of foods. Research has found that high levels of AGEs in your body can lead to a decline in the functioning of your organs and may even contribute to various chronic diseases like Alzheimer’s, sarcopenia, and renal disease. Dietary modification, exercise and pharmacological therapies ways to reduce AGE levels in your body but more research is needed to determine the most effective strategy. Read more

This study had tried to find a connection between the receptor for advanced age glycation products and also patients who are suffering from Lupus and Lupus Nephritis. It was a study that was based on genetics. Different forms of a gene were studied and tracked in a group of patients who had Lupus, patients who had lupus nephritis, and patients who did not have either disease and were considered to be healthy controls. There were significant forms of the gene that were considered to be increased in both Lupus and Lupus Nephritis patients. This may open doors to find links between these advanced age glycation products and other autoimmune diseases for which there is no cure yet. Read more

Proteins suffer increased damage by glycation, oxidation and nitration in diabetes and the glycated, oxidized and nitrated amino acids formed by the proteolysis of plasma may be part of the pathway for the development of microalbuminuria and/or early GFR decline. Read more

In this study, the roles of receptors for advanced glycation end-products (RAGEs) and high-mobility group box 1 (HMGB1) in the regulation of autophagy (cellular self-destruction) was evaluated for their potential contributions to clear cell renal cell carcinoma (ccRCC). It was determined that RAGE/HMGB1 could be a future therapeutic target. Read more

T1D’s have a higher level of circulating RAGE receptor (soluble receptor for advanced glycation end products). This occurs because in T1D there is less of the receptor embedded into the cell membrane (transmembrane full-length receptor). This can contribute to complications experienced by T1D’s, particularly diabetic nephropathy. Read more

A.G.E.s & My Blood Vessels

Vasculature Implications

In the vasculature, A.G.E.s stick to vessels leading to their blockage. They are also found fastened to proteins that are found in the vasculature such as blood cells leading to their dysfunction and disease (14).

Vasculature Research

In patients suffering from CKD, calcification of certain arteries is a strong predictor of cardiovascular morbidity and mortality. This study shows how AGEs can impact the development of this calcification which can lead to severe cardiovascular events. Based on the study, AGE intensity could be used as a predictor of arterial calcification as well as cardiovascular mortality in CKD patients. Read more

Skin autofluorescence, a method used to determine the level of AGEs in the body, may have the potential to be used as a non-invasive measurement of atherosclerosis, a common complication in Type II diabetics where fatty plaque builds up in the lining of the arteries. Read more

AGEs are believed to play a role in development of vascular complications in patients with diabetes. Specifically, a protein called LDL (fat and protein) in the body bound to AGEs has been shown to trigger the immune system. Read more

The AGE arm scanner can quickly and painlessly measure the AGE levels in your blood. These AGE levels can then be used to measure your risk for developing common type 2 diabetes complications. Read more

Increased levels of sRAGE might be a sign of a decrease in AGE-related inflammation and other diseases mediated by inflammation. Increased levels of sRAGE were observed in individuals with increased physical activity. This could explain why physical activity is beneficial for preventing inflammatory diseases such as CVD. Read more

Skin auto-fluorescence (SAF) is used to measure AGEs, and this new method of SAF measurement was successful in determining diabetic complications in Asian type 2 diabetes mellitus (T2DM) subjects, particularly microvascular. Read more

Studies have shown that cardiovascular diseases with progressing atherosclerosis are the most important causes of death in diabetes, and conversely, that diabetic patients have high incidence of atherosclerotic diseases. AGE concentration is directly related to severity of certain cardiovascular diseases, so AGE measurement could be a highly accurate predictor of atherosclerosis in diabetic patients. Read more

The accumulation of advanced end glycation products can be measured via skin autofluorescence. A study in Japan was done on 105 type one diabetics to find a correlation between Type One Diabetes and atherosclerosis in relation to the skin autofluorescence. The study concluded that there was a significant correlation between the skin autofluorescence and the atherosclerosis, meaning the higher the skin autofluorescence the higher the risk of atherosclerosis and Type one diabetics had a much higher skin autofluorescence level. Read more

A study was done to determine if advanced end glycation products were linked to vascular complications in diabetics. The study concluded that AGEs proved useful for tracking the vascular complications for diabetics as well as predicting them. Read more

A study was done to determine the role of advanced end glycation products on diabetic atherosclerosis. They studied the patients for ten years and watched the sclerosis of the arteries during this course. The study found that the advanced end glycation products affected atherosclerosis and even the specific ones had their own varying degree of negative effect on the arteries. Read more

A study was done to determine the effects of advanced end glycation products on type two diabetic mice and their vasculature. They looked at the resistance on an arteriography. During the course of the study, they were able to make a link between advanced end glycation products and vascular resistance. Read more

Advanced Age Glycation Products have been seen to be markedly increased in patients who have diabetes and may now as a result of this study be associated with an increased chance of developing in stent restenosis. It is essential that AGE levels are taken into consideration in diabetic patients for restenosis and for a myriad of other potential consequences of diabetes. Read more

Skin Autofluorescence can be used as a marker in order to detect Diabetes Mellitus and the oncoming atherosclerosis. Read more

A.G.E.s & My Reproductive Organs

Reproductive Implications

High A.G.E. levels in the reproductive organs is associated with the development of aggressive forms of prostate cancer and erectile dysfunction (10).

The receptor for advanced glycation end products (RAGE) is a receptor found on the surface of cells. It has already been shown that when RAGE interacts with advanced glycation end products (AGEs) that it leads to cellular responses that promote the cancer. This study specifically looked at variations in the gene for RAGE and whether there was an association with a risk of epithelial ovarian carcinoma (EOC). They found that one of the variations for RAGE had a significant association with EOC. Read more

This study explored the potential therapeutic benefits of targeting receptor for advanced glycation end-products (RAGE) to treat endometrial cancer. Their data ultimately showed that RAGE-targeting antibody-drug conjugates (ADCs) could be an efficacious and suitable approach to this therapy. Read more

In this study, pregnant rats were given a diet that was either high in Advanced Glycation Products and or low in AGEs. It was seen in the mothers who had low AGEs in their diet, had less immune cells that were attacking pancreatic beta cells, had higher levels of insulin and proinsulin, and also just had lower levels of Advanced Glycation Products in both the mother and the offspring. As a whole, the low AGE diet may potentially provide therapy for those that suffer from Type 1 diabetes. Read more

A.G.E.s & My Bones

Musculoskeletal Implications

A.G.E.s are found in bones, cartilage, muscles, tendons, ligaments, and nerves, where they are associated with osteoporosis, osteoarthritis, sarcopenia, tendinopathy, and neuropathy (11).

Bone Research

There may be a link between the formation of AGEs and the initiation of autoimmune disorders, such as rheumatoid arthritis. Read more

Regular consumption of drinks that are high in fructose may be associated with young adult arthritis in those 20-30 years of age. Unabsorbed excess free fructose may interact with other dietary products in the gut to form AGEs that can cause inflammation of the gut and joints. Read more

Rheumatoid arthritis occurs when someone’s body mistakes its own immunoglobulin IgG as an intruder. The body will make IgM and IgA against its own IgG and cause severe inflammatory effects. When IgG is transformed to AGE-IgG, it may be more likely to induce IgM and IgA to attack it and cause chronic inflammation. Read more

AGE levels in bones can contribute to fragility and cause an increased risk of bone fracture. Read more

As humans get older their bones begin to deteriorate slowly as they age; researchers have found that AGEs are one of many contributing factors to bone deterioration and they believe that aminoguanidine and pyridoxamine, which prevent AGE formation, could be used to improve bone quality and function. Read more

Staying consistently active and eating a diet consisting of fruits, vegetables, and fish can help lower your AGE levels. Read more

Elevated serum AGE is observed in moderately to severely disabled older women who have poor grip strength. This is consistent with the general concept that AGE plays an important role in changes observed in some diseases. Read more

Studies have suggested that elevated levels of advanced glycation end products (AGEs) may be associated with deceased exercise and physical functioning in older adults. Read more

It is thought that the accumulation of AGEs inside the human body may be contributing to a decline in the muscular strength and physical functioning of older adults. Physicians could potentially track AGE levels in patients and intervene with dietary modifications to reduce AGEs and with functional training and muscle strengthening routines to prevent a decline in physical activity. Read more

Adult-onset Still’s disease (AOSD) is an inflammatory disorder resulting in fever, rash, arthritis, and other complications. Anti-glycation end products (AGEs) are elevated in patients with AOSD, which is related to the inflammatory characteristics of AOSD. The level of AGEs present in an individual with AOSD could be indicative of how severe their symptoms/clinical manifestations have the potential to become. Read more

High blood sugar levels in diabetes could lead to increased AGE formation. This AGE formation could be a cause of plantar fasciitis in diabetic patients. Read more

Serum AGEs were positively correlated with cortical and trabecular bone AGEs but more data is needed to determine if AGEs are correlated with diabetic skeletal fragility. Read more

AGEs accumulation might be one of the reasons of impaired lower limb muscle function in Japanese patients with type 1 diabetes. Read more

AGEs antibodies may be higher in people with early synovitis. Read more

This study shows that there might be a relationship between AGE-mediated tissue damage in the joints of patients with osteoarthritis, particularly of the knee, which could also contribute to its association with diabetes. Read more

This study showed that there are highly specific increases in the levels of two advanced glycation end-products in patients with rheumatoid arthritis. This increase could not be explained by either rheumatoid arthritis activity or by inflammation. Read more

Type 1 Diabetes is an autoimmune attack on the Beta cells in your pancreas. This does not allow your body to create insulin, which is a hormone that brings down your levels of glucose. One of the complications of diabetes is decreased bone healing. This study found that mice that had decreased healing rates after they were treated with AGE in their serum. In our healthcare system trying to delay the amount of bone loss that occurs in these situations, AGEs may be a significant topic of interest. Read more

Both Rheumatoid Arthritis and Osteoarthritis plague our world today, with many people suffering from these diseases. Advanced Glycation Products are exacerbated under Oxidative Stress. Through this study, oxidative stress was measured quantitatively through the CML marker. The CML marker was found to be elevated in both rheumatoid arthritis and also osteoarthritis. This may be an area of interest for lowering the amount of AGE that is in the body as in that it could have an effect in reducing some of the symptoms of both Rheumatoid Arthritis and Osteoarthritis. Read more

Bone deterioration is a known complication of type 2 diabetes. A study was done to determine the involvement of advanced end glycation products in this process. The results of the study suggested that AGEs in type 2 diabetes contributed to low bone strength. Read more

A study was done on type two diabetics to determine the role advanced end glycation products played in shoulder pain and disability. The study found that type two diabetics had 23% level shoulder activity. However, they were unable to determine the exact relationship of the elevated AGE’s and shoulder mobility, but there seems to be some correlation. Read more

Advanced Glycation Products are now associated with poorer bone development in addition to diabetes and cardiovascular disease. Therapeutic targeting of AGEs may help strengthen bones. Read more

AGE accumulation in patients with type 2 diabetes has a correlation with sarcopenia and dynapenia, which are syndromes involving decreased muscle strength and mass. These conditions, in turn, put patients at risk of incidental falls. Patients with type 2 diabetes who are >65 years old are at an even greater risk of developing these conditions. Read more

A.G.E.s & My Gut

Gastrointestinal Implications

In the gastrointestinal tract, inflammation caused by high AGE levels is associated with irritable bowel syndrome (IBS) and possibly cancer (9).

There are more AGEs in people with Crohn’s disease, so AGEs could make people develop worse CD. How AGEs do this is not known. Read more

Poor diet and lifestyle exposures have been heavily implicated in the risk of colorectal cancer. The authors of this study hypothesized there will be a positive correlation between circulating glycer-AGE and colorectal cancer. Their research showed there was no statistically significant correlation between glycer-AGE circulation and colon cancer, but there was a significant correlation between circulating glycer-AGE and rectal cancer, especially in patients who drank alcohol. This result was found using a smaller sample size than the main study which would warrant further research. Read more

Colorectal cancer is a very common form of cancer, the progression of which is partially influenced by our diet. AGEs, being a byproduct of our diets, can play a role in the development of this type of cancer. There are a number of enzymes and proteins involved in AGE destruction that are also involved in the progression of colorectal cancer. Glyoxalase-I (GLO-I), AdipoR1, and AdipoR2 are examples of these enzymes. GLO-I is involved in the destruction of these AGEs, and this study showed that high GLO-I levels are directly associated with colorectal tumor progression by cancer stage. AdipoR1 is a receptor involved in hormone signaling, and this study showed that it serves a protective role in normal tissue to prevent the formation of colorectal tumors. AdipoR2 is a similar receptor to AdipoR1 but works in a different way. This study found that AdipoR2 activation was associated with further progression of colorectal cancer. This study showed that AdipoR1, AdipoR2, and GLO-I, all of which are all proteins/enzymes involved in the AGE destruction pathway, can potentially be used as future targets for chemotherapy to help treat colorectal cancer. Read more

A.G.E.s & My Pancreas

Pancreatic Implications

In the pancreas, high levels of A.G.E.s lead to degeneration of the beta cells which are critical in controlling pancreatic function and are also involved in pancreatic cancer (6).

Pancreatic Research

AGEs may contribute to the development of Type I Diabetes. Read more

Diabetic children showed elevated levels of skin AGEs and this may be due to genetic/environmental factors rather than high blood sugar. Read more

Reducing dietary AGEs throughout pregnancy as well as the early life of rats may reduce their susceptibility to type 1 diabetes. Read more

AGEs that are common in the food we eat everyday have been found to promote weight gain, fat gain, and changes to metabolism. These symptoms are very common in type II diabetes. Reducing the amount of AGEs consumed can restore native resistance to the T2D and other diseases linked to high oxidative stress. Read more

Children and adolescents with type 1 diabetes showed higher levels of skin AGEs. Older adolescents, both with and without diabetes, showed higher levels of skin AGEs, as well. Read more

A mother who is pregnant can pass a high number of AGEs to their baby by consuming AGE-rich foods while pregnant. This combined with infants consuming AGE-rich infant foods, may lead to a higher chance of disease in the child, especially diabetes in young people. Read more

Lowering AGEs in the diets of subjects with Type 2 diabetes has shown to improve insulin resistance; raising plasma insulin levels almost back to normal. Reducing the amount of AGEs one eats by boiling, poaching, stewing, and steaming their food can improve the metabolic state of that person. Read more

Excess oral AGE intake in the diet leads to diabetes-like disease. Food-derived AGEs were found to cause inflammation in the body like the inflammation seen in type 1 diabetes in pancreatic islet B-cells. Read more

Methylglyoxal (MG) is a compound that your body accumulates when you eat food, and it can lead to the formation of advanced glycation end products (AGEs) inside of your body. When AGEs form, they are stored in your body, and as more research has been conducted on AGEs they are being recognized as something that can potentially lead to and worsen diseases such as diabetes. There is current research being done to make new therapies that will enhance your body's ability to naturally get rid of MG and AGEs. Read more

The Autofluorescence Reader (AFR) is a tool that researchers and physicians can use to painlessly measure the levels of advance glycation products (AGEs) in your skin. Measuring the AGEs in skin is important as it may help doctors assess diabetic patients risks of developing high blood sugars or kidney failure. Read more

Physical activity helps older adults live healthy and longer lives. Research suggests that one of the benefits of physical activity is that it can reduce the amount of sRAGE in your blood, a molecule that contributes to inflammation, diabetes, and various other disorders. Read more

AGEs were found to modify fat tissue to contribute to insulin resistance associated with diabetes mellitus. Read more

In patients with type 2 diabetes, it was found that higher levels of AGE accumulation were present than those who were healthy. Read more

The goal of the investigators in this study was to determine the role of advanced glycation end-products (AGEs) in pancreatic cancer. They found that reducing AGEs might decrease the pancreatic cancer risk that is associated with diabetes mellitus, obesity, western diet, and tobacco smoking. Read more

There is a well-known link between diabetes/hyperglycemia (high blood glucose) and developing certain cancers, but the actual effects of hyperglycemia on cancer is not well-known. It is known, however, that advanced glycation end-products (AGEs) are formed as a result of chronic complications of hyperglycemia, which in turn are linked to tumor growth. The potential role of the receptor for advanced glycation end-products (RAGEs) mechanisms in tumor progression has yet to be determined. Read more

A study was done on a group of Type 2 Diabetics to determine if advanced end glycation products cause insulin secretion defects. The results of this study suggested that advanced end glycation products were correlated negatively to Type 2 diabetics having insulin secretion defects. Read more

A study was done with mice to determine the effects of AGE diets on insulin producing cells in the pancreas. At the end of the study, they determined that mice who were fed a low AGE diet and mice on a high AGE diet had no difference in the insulin production in these cells. Read more

Older adults with type 2 diabetes over the age of 65 following a diet to lower glycemic index and AGEs by modifying the way they cooked their food. After 6 months of following this diet, a drop in AGEs in their blood was seen. Read more

Advanced glycation end products (AGE’s) bind to receptor advanced glycation end products (RAGE’s) in Type One Diabetes Mellitus the amount of RAGE’s is markedly increased. In addition, the inflammatory markers were increased in these patients compared to the control. However, they are also increased with at-risk relatives prior to the onset of disease. This suggests that the increased levels predate dysglycemia and may account for the immune response. Read more

An analysis of multiple studies was done to determine the relationship between gestational diabetes and advanced end glycation products. The analysis of the studies concluded that there was a strong relationship between the level of AGE’s and the potential development of gestational diabetes. Read more

A study was done on type two diabetic patients to determine the correlation of vitamin D levels and advanced end glycation products. In the study they gave random patients either vitamin D or a placebo. They study concluded that vitamin D status is independent of advanced end glycation products in well controlled type two diabetics. Read more

One of the therapeutic strategies to diabetes is to monitor glucose levels to make sure the medication and insulin that the person is taking is efficient in decreasing the levels of glucose in the blood. In this study, both in vitro and in vivo studies were done in order to induce the formation of fluorophores (which are easy to see because of their fluorescent property). These can be used to monitor the glucose levels since they are directly related to the hemoglobin getting glycosylated. This study is one step forward in helping patients monitor their diabetes. Read more

Dietary advanced glycation end products (dAGEs) consumption has been associated with increased oxidative stress and inflammation.This study showed that restricting dAGE in patients with type 2 diabetes decreased TNF-α and malondialdehyde levels, both of which are involved in inflammation and diabetic complications. Dietary modifications are necessary in reducing dAGE intake and thus reducing the risk of diabetes and diabetic complications. Read more

A.G.E.s & My Liver

Hepatic Implications

The liver is where most A.G.E.s accumulate! Here they are associated with fatty liver disease, fibrosis, cirrhosis and cancer (7).

One study focuses on how AGEs are associated with liver cancer cells. It was shown that AGEs can accelerate the growth of liver cancer cells, as well as suppress the body’s natural ability to kill cancer cells before they become an issue. Read more

Advanced Glycation Products have been previously linked to both diabetes and cardiovascular disease and now through this study has been also linked to AA amyloidosis. This can be used for various therapeutic measures and also drug development. Read more

A.G.E.s & My Breast

Mammary Implications

A.G.E. levels have been shown to be high in the breast of breast cancer patients and may alter breast development during puberty (13).

Elevated AGE levels are seen in malignant breast cancer tissue when compared to non-cancerous breast tissue, implicating AGE in development of cancer. AGEs can also potentially interfere with a common treatment for breast cancer, tamoxifen. The effect of this drug on ER+ breast cancer, which comprises 70% of invasive breast cancers, was shown to be lessened when higher amounts of AGE are added to the sample. Read more

AGEs (Advanced Glycation End products) and RAGE (Receptor for Advanced Glycation End products) may play a role in the progression of breast cancer. While there are some predictors for long-term breast cancer outcome, this study showed that different variations of RAGE and glyoxalase 1 (a protein that removes AGE precursors) could be strong predictors as well. Read more

A.G.E.s & My Thyroid

Endocrine Implications

A.G.E.s have been shown to increase oxidative stress and inflammation in the thyroid leading to increased risk of thyroiditis and cancer (3).

Oxidative Stress is a phenomenon that is behind many of the autoimmune conditions that we see in the world today. One such autoimmune condition is Hashimoto’s Thyroiditis. In this study, the amount of markers for oxidative stress were measured including Advanced Glycation End products (AGEs). The amount of these products was higher in those patients with the autoimmune conditions than those with the controls. It therefore may be a target of many drugs in the future that may help some of these patients to find relief. Read more

The process of glycation is disturbed in people with Graves’ orbitopathy and it is shown that people with this disease have a significantly lower amount of AGEs compared to healthy individuals. Methylprednisolone significantly lowers the concentration of advanced glycation end-products and may affect the formation or removal of AGEs. Read more

A.G.E.s & Me