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Aging and Inflammation

By: Peter T. Pugliese, MD
Posted: November 24, 2009, from the December 2009 issue of Skin Inc. magazine.

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Tissue may not be destroyed, but it is definitely altered so that it does not function as well. Cells and cytokines of the innate immune system are the culprits, with the macrophages being the central cells in chronic inflammation. They interact with lymphocytes, secrete factors involved in tissue injury (ROS, proteases, inflammatory mediators), clean up debris and coordinate the granulation tissue response by inducing angiogenesis, the production of new blood vessels, by secreting fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF).

It seems apparent that oxidative stress underlies the aging processes, but strong evidence indicates that calorie restriction (CR) reduces age-related oxidative stress and at the same time, produces anti-inflammatory properties.2 Exactly how all this ties together is not fully established, though the biochemical and molecular bases of the inflammatory effect in the aging process points to some key players. Investigators have identified the following biochemical reactions in aging: the upregulation of NF-κB and increased production of the cytokines interleukin-1 beta (IL-1 β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). In addition, two enzymes—cyclooxygenase-2, a major inflammation-producer, and inducible nitric oxide synthase (iNOS)—have been implicated as significant players in inflammatory reaction. It has been found the CR is able to attenuate all of these processes. The term “molecular inflammation” has been used to describe this process. See Figure 1.

Keep in mind that the inflammatory response is really the body’s defensive response via the immune system to combat injury or infection. Inflammation is now beginning to be seen as the root cause of most chronic diseases, from arthritis to cancer.3 See Diseases and Chronic Inflammation. Many factors have a role in inflammation, one of which is glycation, a process that directly stimulates NF-κB. This reaction results in a cascade of events, including mitochondrial energy depletion, calcification (mainly of blood vessels), fatty acid imbalance, marked immune dysfunction and oxidative stress. A serious complication of these processes is the appearance of autoimmune diseases, which are known to increase with age and are closely related to the aging process, with inflammation being the most significant factor. Rheumatoid arthritis is an autoimmune disorder in which high levels of the inflammatory cytokines, such as TNF-α and IL-6, are present, along with a new one, interleukin-8 (IL-8).

Prevention

It’s pretty clear from all this information that by suppressing inflammation, aging can be slowed down or even prevented. How can you help correct this problem in clients when the immune system is so intricately bonded with the body’s life-saving defense system?

Obviously, diet plays a major role, not only for good health, but also as a major factor in the genesis of disease. First, however, consider the major changes that need to be made if your clients really want to counteract the insidious causes of aging. Clients can’t do much about their genetic background—they are stuck with that—but the right choices about what they do and what and how they eat can be made. Basic scientific studies appear to confirm that CR is the best bet.