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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.
  • Glycation, the binding of a protein molecule to a glucose molecule, causes many aging symptoms.
  • Oxidative stress can also cause several signs of aging in skin.
  • Additionally, sun exposure can cause both glycation and oxidative stress-related skin aging.

Despite many years of intense research on the cause of aging, it is still not fully understood, although general consensus is that chronic inflammation appears to be a major underlying factor. It is known that aging is a complex process that has both genetic and environmental components. It is also known that, in many cases, aging is not systemic.

The process of aging results in an increase of inflammatory cytokines, which are chemicals that are cell signals responsible for many of the degenerative diseases associated with aging.1 Rheumatoid arthritis is a classic chronic inflammatory disease associated with excess levels of cytokines that include tumor necrosis factor-alpha (TNF-a) and interleukin-6 and NF-kappaB (NF-kB), which are known to cause or contribute to the inflammatory syndrome. In this article, the three known causes of chronic inflammatory disease associated with aging will be addressed, including NF-kB, oxidative damage and the effects of ultraviolet (UV) light on the skin.

NF-kB

NF-kB is a critical compound in body protection—and in the initiation of inflammation. When it is in excess or if it is stimulated by some pathological condition, it can produce both acute and chronic inflammation.2

One of the compounds that is capable of stimulating NF-kB production is known as an advanced glycation end product (AGE). Glycation is the binding of a protein molecule to a glucose molecule, or a fat molecule, resulting in the formation of abnormal protein structures. Many known age-related diseases, such as cataracts and neurological impairment, are at least partially attributable to glycation. These glycation end products contain reactive chemical groups that can combine with proteins and lipids and cause insoluble complexes.3 These complexes, while biologically active, are physiologically abnormal and thus are capable of entering into cellular reactions that are related to the production of inflammatory components, particularly the cytokines. Foods that are cooked above 140°C will undergo glycation. Frying, baking, broiling and roasting all are done at temperatures in excess of 300°C.

One of the ways the action of NF-kB can be avoided is to decrease the intake of AGE products. Although this may seem to be an extremely difficult change in the diet, it actually is not quite that bad. As of now, the safe amount of intake of glycation products is unknown. Consider that 100 g of roast chicken skin contains more than six million glycation units.

Cooking foods at high temperatures results in a browning effect, where sugars and certain oxidized fats react with proteins to form glycation products in the food. A person’s diet plays a major role in chronic inflammatory processes.4 Eating too much overcooked food causes an increase in inflammatory cytokines, which can lead to chronic inflammatory disease. It is known that junk foods are cooked at extremely high temperatures, so avoid french fries, hamburgers, potato chips, fried foods and other snacks.

Oxidative Damage

Free radical damage was one of the first processes associated with aging; it actually goes back to the 1950s when Denham Harman, MD, PhD, first proposed oxidation as a mechanism for tissue destruction. The aging process is a deterioration of metabolic balance, or homeostasis; therefore, aging is accompanied by an alteration in the impairment of physiological systems, such as the immune system. One target of oxidative damage within the cell is an organelle known as the mitochondria, which applies the major portion of energy to the cell and also consumes more than 90% of the oxygen coming into the body.

It is interesting that this oxidation-mitochondrial process is associated with aging, and that the age-related changes of immune functions have their basis in oxidative and inflammatory stress situations. These have among their intracellular mechanisms the activation of NF-kB in immune cells. Now the relationship between oxidation and immune function can be seen, as can the relationship between that process and the production of NF-kB in immune cells. This association adds a great deal of weight to a relatively new theory of aging known as oxidation-inflammation.5

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, multiple sclerosis and 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.