August 21, 2007

Aging, Immunity, Inflammation and Glycation

serial photos as we grow olderIt has long been known that the level of proinflammatoy cytokines such as interleukins 1,6 and tumor necrosis factor-alpha rise with age, so does inflammatory diseases like cancer, arthritis, with age. Sleep, exercise and other healthy lifestyles lead to a decrease in the level of these substances. For example sleep reduces TNF-alpha, IL1 and IL6, whereas exercise causes a decrease in the acute phase reactant, c-reactive protein (CRP), a substance typically associated with inflammation.

While immunity plays a vital role in protecting our bodies against foreign invaders, excess of it can damage us. There are even some situations where our bodies are unable to distinguish between self and non-self (foreign) proteins, due to a defect in immunity. It then turns itself on against our own proteins. Some researchers argue that this might play a role in aging. Indeed, autoimmune diseases become more frequent with age.

Another contributing factor in aging is glycation. Glucose can bind with non-glucose molecules to form different molecules, this reaction is called glycosylation. Enzymes, catalytic substances, can facilitate this reaction. However, glycosylation can also occur non-enzymatically, it is then known as glycation. In diabetes, we measure the glycated hemoglobin content (HbA1c) to have an overall (and integrated) view of blood sugar control, for the preceding 2-3 months. This is because of two reasons: since the red blood corpuscles (RBC) live for about 120 days, the hemoglobin (Hb) can also be thought of for living as many days; and that glycation reactions being independent of enzymatic activity, will thus reflect the blood sugar concentration. Glycated end products (AGE or advanced glycosylation end products) are frequently referred to as Amadori products, Maillard reactions or Schiff bases; though minute differences exist among them. It is expected that in diabetes, where the blood glucose levels remain elevated, the glycated products will be more. These are responsible for microvascular complications of diabetes such as diabetic nephropathy (kidney/renal failure) and diabetic retinopathy (may lead to blindness). These damages result from AGEs and glucose combining with protein molecules in such a way that these protein molecules become extensively cross-linked. As a result, the protein shape (conformation) changes: they may clump together or their functions may reduce, as a result. Diminution of function is due to its change in structure, both secondary and tertiary (folding), as protein function depends not only on the sequence of its constituent amino acids, but also the way the are arranged in space. Aspirin, carnosine, alpha lipoic acid and some other substances inhibit glycation. On the other hand, synthetic molecules, such as Alt711 can break the cross-links which have already formed. These agents may help us combat aging by interfering with glycation. Thus it is evident that glycation will leave its imprint on aging, by interfering with cell function.

Related posts: Aging: From a General and Evolutionary Perspective; Aging, Mitochondria and Free Radicals; Hayflick limit, Telomere and Aging
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