Glycation in Diabetes and Aging: Routes to Life Extension and Longevity

High blood sugar levels, as are seen in diabetes, insulin resistance, and other forms of hyperglycemia, leads to a process called glycation. Glycation changes the shape and properties of proteins. Crosslinking reduces the flexibility, elasticity, and functionality of the proteins. Furthermore, the chemical modifications of glycation and crosslinking can initiate harmful inflammatory and autoimmune responses. "AGE and nonenzymatic crosslinks are demonstrated to signal inflammatory cytokines, extracellular matrix expansion, angiogenesis, and growth factors." [deGroof] Glycation has been found in connective tissue collagen, arterial collagen, kidney glomerular basement membrane, eye lens crystallins, nerve myelin proteins and in the circulating low-density lipoprotein (LDL) of the blood.

Prolonged glycation leads to creation of advanced glycation end products, AGE. The end result of AGE is all the deadly complications that lead to excessive morbidity and mortality in diabetic patients. Blindness, renal failure, arteriosclerotic heart disease, neuropathies, loss of limbs, etc.

What is not generally known, is that the same process of glycation and AGE formation occurs in normal people, at a much slower rate. You may think that that giant soda, or huge piece of pie is not doing anything bad to your body, but you would probably be wrong. Your connective tissues are being cross-linked beneath your level of awareness. You are ageing prematurely.

This article in Scientific American discussed this issue a few years ago. This brief background article gives more information, with links to more sources.

Various drugs and nutriceuticals have been used to treat glycation and AGE. This article discusses the use of ginger in preventing diabetic kidney damage.
An estimated 19 million people are affected by diabetes in the EU, equal to four per cent of the total population. This figure is projected to increase to 26 million by 2030.

The rhizome of the ginger plant (Zingiber officinale) is a rich source of antioxidants, including gingerols, shogaols, zingerones and other ketone derivatives. It has long been used as a remedy for nausea, especially associated with morning sickness.

The new study, published on-line in Food Chemistry (doi: 10.1016/j.foodchem.2006.01.013), assessed the effects of ginger on the blood antioxidant levels and kidney health of diabetic rat models.

Twenty-four male rats were divided into three groups of eight. The first group (control 1) were healthy rats, the second group (control 2) were diabetic and non-supplemented, and the third group (test) was diabetic and had the diet supplemented with ginger powder as five per cent of the daily food intake.

After eight weeks of supplementation the researchers, led by Dr Ali Taghizadeh Afshari from the Emam Khomeini Hospital, reported: “Antioxidant capacity in the ginger supplemented rats was higher when compared to the other groups.”

The primary drug used to treat glycation and AGE is aminoguanidine. Over the counter nutraceuticals used to treat AGE include carnosine, pyridoxamine, and various forms of thiamine. Ginger may also provide some benefit in preventing diabetic complications, but that research is ongoing.

Glycation end products also accumulate in the brain in Alzheimer's Disease. Scientists are still trying to define any relationship between AGE accumulation in the CNS and neuronal apoptosis. The recent discovery that lower brain insulin may predispose to Alzheimer's Disease probably has something to do with accumulation of AGE.

I will be writing much more on this topic in the future, since it is of great importance in the overall strategy of retarding the ageing process.