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Aging and Inflammation

By: Peter T. Pugliese, MD, and Michael Pugliese
Posted: October 26, 2012, from the November 2012 issue of GCI Magazine.

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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 and 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.

Histological changes of chronological aging skin show thinning of the stratum spinosum and some flattening of the dermo-epidermal junction. The sun-protected epidermis, on the other hand, shows epidermal thickness that is increased in sun-exposed skin. Why this thickness occurs remains unknown, though it is believed to be associated with some cellular mechanism that prevents apoptosis, or programmed cell death.9 Growth factors that are associated with inflammation may contribute to early tumor formation. As an example, melanocyte growths are seen as a result of the inflammatory process producing nevi and other pigmented lesions, as well as hypomelanosis, which can occur in photoexposed areas. This accounts for a great deal of the immune damage visible after sun exposure that is intense enough to result in a burn.

In the dermal region of aging skin, a reduced number of fibroblasts are generally found that not only produce less collagen than younger fibroblasts but also produce more collagenase, the enzyme that destroys collagen. It appears that this is one of the major reasons that aging skin sags, as well as one of the reasons that reconstructing aging skin is so difficult. Of course, the amount of elastin in sun-damaged skin associated with aging is increased, but functionally is quite abnormal; aging skin shows histological changes that include an increased amount of cross-linking of collagen fibers.

Although this cross-linking is an enzymatic process, there is also associated nonenzymatic cross-linking that appears to be due to glycation. Both of these processes are characteristic of photodamaged skin. The amount of UV light reaching the dermis depends both on the duration of exposure and on the intensity of the radiation. For example, UVA, although it penetrates deeper into the dermis than UVB, is more frequently associated with collagen damage and aging changes, while UVB damages the epidermis most frequently and is a major cause of skin cancer.

The radiation intensity from UVB is 1,000 times stronger than that of UVA radiation. Skin changes resulting from chronic UV exposure show classic collagen changes with the increased levels of collagen Type III, along with abnormal, thickened, tangled and nonfunctional elastic fibers. Eventually these tissue changes result in tissue that is degenerated into a nonfibrous, amorphous mass—a finding known histologically as solar elastosis.10 It is this process that produces classic sun-damaged skin seen in inveterate sun worshipers.

The bottom line is that there is no safe way to tan, because increased pigmentation appears to be a sign that some degree of inflammation has taken place.

For additional information on inflammation and aging, read “Inflammation and Aging” and “Examining Skin: A Functional Barrier” by Marie Alice Dibon.

References

  1. AA Podtelezhnikov, et al, Molecular insights into the pathogenesis of Alzheimer’s disease and its relationship to normal aging, PLoS One, 6(12), :e2961 (2011)
  2. SC Gupta, et al, Role of nuclear factor B-mediation in inflammatory pathways in cancer-related symptoms and their regulation by nutritional agents, Exp Biol Med, 236(6), 658–671 (Jun 1, 2011)
  3. DR Sell, Molecular Basis of Arterial Stiffening: Role of Glycation, Gerontology (Jan 4, 2012)
  4. A Anogeianaki, et al, Atherosclerosis: a classic inflammatory disease, Int J Immunopathol Pharmacol 24(4), 817–825 (Oct 2011)
  5. R Tacutu, et al, Molecular links between cellular senescence, longevity and age-related diseases—a systems biology perspective, Aging (Dec 18, 2011)
  6. S Le Saux, et al, Mechanisms of immunosenescence: lessons from models of accelerated immune aging, Ann NY Acad Sci (Jan 6, 2012)
  7. TC Squier, Oxidative stress and protein aggregation during biological aging, Exp Gerontol, 36(9), 1539–1550 (Sep 2001)
  8. N Pustisek and M Situm, UV-radiation, apoptosis and skin, Coll Antropol, 35 Suppl 2, 339–341 (Sep 2011)
  9. J Krutmann, et al, Sun Exposure: What Molecular Photodermatology Tells Us About Its Good and Bad Sides, J Invest Dermatol (Dec 15, 2011)
  10. L Baillie, et al, Strategies for assessing the degree of photodamage to skin: a systematic review of the literature, Br J Dermatol, 165(4), 735–742 (Oct 2011)