Inflammation

The processes of inflammation are a potent source of age-related cellular damage, as this first article reminds us:

Chronic inflammation spurred by an immune system run amok appears to play a role in medical evils from arthritis to Alzheimer's, diabetes to heart disease. There's no grand proof of this "theory of everything." But doctors say it's compelling enough that we should act as if it were true -- which means eating an "anti-inflammatory diet," getting lots of physical activity, and losing the dangerous, internal belly fat that pumps out the chemicals that drive inflammation

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Chronic inflammation is so similar in different diseases, Libby said, that when he lectures, he uses many of the same slides, whether he's talking about diseases of the heart, kidneys, joints, lung, or other tissues.

Only a few years ago, heart attacks were explained as a plumbing problem -- blood vessels that became clogged with atherosclerotic plaque as "bad" (LDL) cholesterol was deposited on vessel walls. Now, doctors know that this bad cholesterol gets embedded inside artery walls as well, where the immune system "sees" it as an invader to be attacked. The ongoing inflammation in arteries, essentially a revved up immune response, can eventually damage arteries and cause "vulnerable" plaque to burst. It is because inflammation is now seen as such a hallmark of heart disease that many doctors use a test for inflammation called CRP to help assess a person's cardiac risk.

It's long been known that type 1 diabetes is linked to inflammation -- the body's immune system attacks the cells that make insulin. Now, new research is suggesting that type 2 diabetes, the kind that generally sets in in adulthood, often begins with insulin resistance, in which cells stop responding properly to insulin. Doctors now know that during chronic inflammation, one of the chemicals released is TNF, or tumor necrosis factor, which makes cells more resistant to insulin.

""No one would have thought these things were related," but they are, said Dr. Walter Willett, chairman of the department of nutrition at the Harvard School of Public Health. The TNF connection also helps explain why obesity, particularly abdominal obesity, leads to diabetes. "Fat cells used to be thought of as storage depots for energy, as metabolically inactive," said Libby. "Now we know that fat cells are little hotbeds of inflammation. Excess fat in the belly is a great source of inflammation."

Autoimmune diseases like rheumatoid arthritis are also believed to be linked to inflammation. In arthritis, for instance, inflammatory cells called cytokines lead to the production of enzymes that break down cartilage in joints.

Inflammation also plays some role in Alzheimer's disease, said Linda Van Eldik, a neurobiologist at the Northwestern University Feinberg School of Medicine.

Whenever the brain is injured or infected, cells in the brain called glia pump out cytokines. Normally, this response shuts down when the injury or infection is over.

"But in chronic neurodegenerative diseases like Alzheimer's, these glial cells are activated too high or too long or both," Van Eldik said. The plaques and tangles in patients' brains attract the attention of glial cells, making them pump out even more cytokines to try to repair this damage and creating chronic inflammation.

Age-related diseases are the final breakdown of a system that has suffered a great deal of cellular, genetic and biochemical damage. Just like any complex machinery, it will break down more rapidly if subject to a higher rate of ongoing wear - such as that provided by inflammatory processes. As scientists uncover and catalogue ever more of our biochemistry, common sense health advice (exercise, stay trim, eat a good diet, take supplements) generally turns out to minimise exposure to chronic inflammation - especially losing the excess fat.

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