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Physiology of the Skin: Aging and Inflammation

By: Peter T. Pugliese, MD, and Michael Pugliese
Posted: February 28, 2012, from the March 2012 issue of Skin Inc. magazine.
Physiology of the Skin: Inflammation and Aging

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Chronic oxidative stress affects all cells, especially cells of the nervous, endocrine and immune systems, as well as the communication between them, and all the processes that involve cellular regulation. Once biological homeostasis is upset, the preservation of health is at peril. A key involvement of the immune system in the aging process of the organism concerns the rate of aging—because there is a relation between the degree of oxidative damage and the functional capacity of the immune cells—and therefore the longevity of individuals. More than 40 years ago, the immune system was proposed as a major target of aging and, only now, are scientists beginning to see the relationship between the immune system and the process of aging linked together by oxidative damage.6 The addition of adequate amounts of antioxidants in the diet improves immune function, decreasing oxidative stress and, consequently, increasing longevity.

Certain neurodegenerative diseases, such as Alzheimer’s disease and multiple sclerosis as well as amyotrophic lateral sclerosis, have been associated with oxidative damage. A major target of oxidative damage is the mitochondria, since approximately 95% of the body’s intake of oxygen must pass through the mitochondria in the process of oxidative metabolism. Because the mitochondria supplies the major portion of energy to the cell, and therefore to the body, any process that damages mitochondria will have a major impact on the body physiology.

Body weakness is often the first sign associated with mitochondrial damage. Because every cell needs a large supply of energy in order to carry out the daily metabolic processes, they will undergo internal damage, eventually resulting in dysfunction of a particular cell, which is then manifested by organ malfunction. There appears to be a rather complex relationship between oxidative damage and protein metabolism that results in cellular damage on a molecular basis.7 Often, this damage is actually produced by the body itself in response to some exogenous or endogenous factor that the body recognizes as a foreign material. For example, a diet high in glycation products, such as that which results from high-heat cooking, can be very harmful to diabetic individuals who have high blood sugars. These sugar molecules will cross-link with proteins and fat molecules to produce an excessive amount of AGEs, which then react with cellular receptors to produce inflammatory reactions. This is one reason that antioxidant and nutritional therapy are being employed in several metabolic disorders in an attempt to reduce this internal stress on the body.

UV damage the skin

There is no question that UV rays have a very adverse effect on skin. Both the epidermis and dermis can be severely damaged by excessive exposure to energy in the range of 290–400 nm, which covers both the UVA and UVB spectra. The skin is one of the major target organs of UV exposure. Within this, the immune system is particularly vulnerable. In the presence of an inflammatory reaction, which is the body’s response to infection or injury, there can be an actual accentuation of the inflammatory mechanism, such that it amplifies the defensive response, which can result in molecular damage to not only DNA, but also to other proteins, such as enzymes and immune-response proteins.8 Some of these responses can actually produce immune suppression, as well as cancer and classic photoaging.

There are many induced immune-regulatory and pro-inflammatory mediators produced by the body at the gene-expression level. A full understanding of the cutaneous immune system’s response to photo-skin interactions is not yet known, but it is essential to fully protect the skin from adverse solar effects. The protection of current sunscreen products is measured only as a reduction in redness (the current SPF value), and this may no longer be sufficient, because it is clear that protection against UV-induced immune changes is of equal—if not of greater—importance. A great deal more information about these processes is needed in order to continue the development of improved strategies to repair photodamaged skin.