The process can be compared to the toughening of leather. Both the meat and hide of an old animal are tougher and stiffer than those of a young animal, because of the AGE-related cross-linking that occurs inevitably with age. As Cerami explains, the aorta, the main artery running out of the heart, is an example of this stiffening effect of accumulated and cross-linked AGEs. “If you remove the aorta from someone who died young,” says Cerami, “you can blow it up like a balloon. It just expands. Let the air out, it goes back down. If you do that to the aorta from an old person, it’s like trying to inflate a pipe. It can’t be expanded. If you keep adding more pressure, it will just burst. That is part of the problem with diabetes, and aging in general. You end up with stiff tissue: stiffness of hearts, lungs, lenses, joints…. That’s all caused by sugars reacting with proteins.”

AGEs and the glycation process also appear to play at least one critical role directly in heart disease, by causing the oxidation of LDL particles and so causing the LDL and its accompanying cholesterol to become trapped in the artery wall, which is an early step in the atherosclerotic process. Oxidized LDL also appears to be resistant to removal from the circulation by the normal mechanisms, which would also serve to increase the LDL levels in the blood. As it turns out, LDL is particularly susceptible to oxidation by reactive oxygen species and to glycation.*57 In this case, both the protein portion and the lipid portion (the cholesterol and the fats) of the lipoprotein are susceptible. These oxidized LDL particles appear to be “markedly elevated” in both diabetics and in nondiabetics with atherosclerosis, and are particularly likely to be found in the atherosclerotic lesions themselves.

That glycation and AGEs are critical factors in diabetic complications and in heart disease has recently been demonstrated by experiments with compounds known as anti-AGE compounds or AGE breakers. These will reverse arterial stiffness, at least in laboratory animals, and, as one recent report put it, ameliorate “the adverse cardiovascular and [kidney-related] changes associated with aging, diabetes and hypertension.” Whether these or similar compounds will work in humans remains to be seen.

When biochemists discuss oxidative stress, glycation, and the formation of advanced glycation end-products, they often compare what’s happening to a fire simmering away in our circulation. The longer the fire burns and the hotter the flame, the more damage is done. Blood sugar is the fuel. “Current evidence points to glucose not only as the body’s main short-term energy source,” as the American Diabetes Association recently put it, “but also as the long-term fuel of diabetes complications.”