About advanced glycation end products

What are advanced glycation end products?

The chemical products of spontaneous reactions between sugars and proteins are known as advanced glycation end products (AGEs). Here we explain what they are and their role in aging.

The accumulation of AGEs significantly contributes to changes associated with aging. As with oxidation, the long-lived proteins of our body accumulate sugar modifications until they can’t do their job any more.

By way of example, the kidneys play an important role in filtering toxic substances from the body, and may be damaged by accumulation of AGEs. Increased blood sugar levels combine with the structural proteins, causing alteration in the morphology of the mesangial cells lining the glomeruli, and therefore resulting in reduced renal function.

The impact of AGEing?

Over a lifetime of cooking, the amount and variety of AGEs-modified tissue progressively increases. High sugar levels, elevated fats and increased oxidative stress all hasten the formation of AGEs, and with it the aging process.

These AGEs modifications interfere with the functions of anything they stick to. Modification can also lead to the formation of cross-links that reduce the flexibility of structures, forming molecules in certain shapes. This is one reason our blood vessels become stiff with age.

The human body has many ways of coping with aging. One is the ability to identify parts that are old and replace them with new parts. But how do you tell an old protein from one you made yesterday?

Well, how do you spot an old leaf on a tree? It will likely be the brown one. Likewise in the human body, browning is one way to tell how long each part has been around, and when its time is up.

Sensing the type and quantity of AGEs modification is the job of the AGEs receptors.

Over recent years a number of AGEs receptors have been identified. Some of these are good receptors, whose job it is to remove AGEs from the body. Other bad receptors are activated by AGEs, triggering a cascade of pathways that lead to inflammation and aging. The best known of these is appropriately known as receptors for advanced glycation end products (RAGE). RAGE activation influences atherosclerosis, cancer, Alzheimer’s disease and diabetes.

How do I slow AGE-ing?

The browning of proteins by sugars is not the only element that leads to aging, but it is one that we can do something about.

Keeping healthy sugar levels is the most straightforward way. A number of widely available supplements may also reduce the accumulation of advanced glycation end products.

Further, most antioxidants have significant AGEs-inhibitory activity. Some, however, have important additional effects. These antioxidants include:

• Thiamine (vitamin B1) can reduce the AGEs generating in the body. Diets high in fibre often contain useful amounts of thiamine. Chronic alcohol consumption can deplete our thiamine reserves, so it is best to avoid this. The best way to get thiamine is to take special forms that have improved absorption properties. These are naturally found in garlic and onions. Botanically, these plants are of the allum family. These chemicals are called allithiamines such as benfotiamine.
• Pyridoxine (a derivative of vitamin B₆) can reduce AGEs forming, particularly those derived from fats. Pyridoxine is safe and well-tolerated as a supplement, and is effective in reducing AGEs levels and preventing some complications of aging and diabetes in animal models.
• Rytine (a natural flavanoid found in high concentration in tomato juice) has the ability to inhibit AGEs formation.
• Carnosine (an antioxidant from meat, typically lacking in a vegetarian diet) inhibits AGEs forming and prevents protein modification by acting as a scavenger.
• Alpha-lipoic acid (highest in foods such as potatoes, carrots, broccoli, beets and yams) is able to prevent the AGE-modification.

Reducing your intake of AGEs

Another way to limit our burden of AGEs is to prevent any unnecessary intake.

Many of the highly-processed foods we eat contain AGEs. This has a number of positive and negative consequences. Browning produces flavours, textures and aromas that give many foods their appeal. For example, the crunch of crisps is conveyed by cooking at very high temperatures and low humidity. Equally, the delicious smell and taste of pork cracking comes from cooking fat at high heat. Sure the chips taste better, not to mention that ‘extra crunch’, but at what cost?

There is a strong relationship between the levels of advanced glycation end products in our blood and the amount consumed in our diets. Essentially, eating AGEs-modified food means you also gain some of these AGEs modifications.

A number of studies have shown a relationship between high dietary intake of AGEs and development of age-related problems. It is possible to significantly lengthen the lives of mice by restricting the amount of AGEs they eat, even if they are allowed to eat as much and as often as they like.

So if we were mice, we’d have two choices to slow aging: eat significantly less processed food or eat as much as we like of the unprocessed fresh diet. This philosophy may not be far off the mark for humans either.

Practical ways to reduce AGEs

• Eat fresh and unprocessed foods
• Eat foods low in fat, especially for cooking
  • Use ricotta instead of yellow cheese
  • Use yoghurt as a cream or sour cream substitute
  • Choose low fat coconut milk instead of coconut cream
  • Choose trim cuts of meat and remove the skin from poultry
  • Cook with a grill instead of frying or baking
• Cooking on a low heat (less than 250C) over long periods of time and in the presence of excess humidity  using methods such as boiling, poaching, stewing, steaming, or using a slow cooker)
• Marinate or use garlic and spices to flavour food rather than browning meat
• Eat foods naturally high in antioxidants, such as garlic, onions, tomatoes, broccoli, beets and yams
• Moderate your alcohol consumption
• Avoid foods rich in fat, particularly trans and saturated fats
  • Read food labels to check for trans fat content (there should be none!)
  • Check the fat content of processed foods
  • Choose low fat options
• Choose a low glycemic index (GI) diet
  • Buy a small reference book with a list of foods with their GI so you can more easily choose low- over high-GI foods
  • Check out the official GI website
  • Avoid ‘white’ foods with high GI such as pasta, potatoes, white sugar and rice
  • Eat more beans and legumes
  • Have a daily serve of nuts
  • Eat a predominately fruit and vegetable-based diet
  • Eat lots of whole grains – choose brown rice over white, wholemeal bread or bread made using whole grains over white bread, whole wheat products over refined wheat foods
  • Avoid bottled dressings
  • If you eat high GI foods, then combine with low GI foods. For example, eat jasmine rice with dhal (lentils)
  • Use vinegar as a vinaigrette, as this will lower the GI of foods

 References

1. Hogan M et al. (1992) Advanced glycosylation end products block the antiproliferative effect of nitric oxide: Role in the vascular and renal complications of diabetes mellitus. J Clin Invest 90: 1110-1115

Last reviewed 03/Mar/2017

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Dr Merlin Thomas

Professor Merlin Thomas is Professor of Medicine at Melbourne’s Monash University, based in the Department of Diabetes. He is both a physician and a scientist. Merlin has a broader interest in all aspects of preventive medicine and ageing. He has published over 270 articles in many of the worlds’ leading medical journals

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