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Proteomics, Exercise and Inflammation

Friday, May 11, 2007


Today’s column addresses questions from our recent ASCRS Eyes on Fire lecture.

Proteomic science is changing the way many gerontologists think about inflammation, the aging process and degenerative diseases. The term proteomics was coined as an analogy to genomics, the study of genes. Understanding the structure and function of each protein and the complexities of protein-protein interactions is becoming critical to the development of effective diagnostics, disease treatments and more importantly, degenerative disease prevention including eye disease.  

Our bodies are designed to replace our cells one at a time through a fairly simply process of deterioration and growth. This brilliant process is dependent on intact DNA and messenger RNA (mRNA), good nutritional status, protein-protein interaction and regular aerobic exercise, which is now suggested to help control the inflammation associated with aging and most degenerative disease.

The proteins that control inflammation are called cytokines (messenger molecules) and they regulate every aspect of our biology by turning on and off the metabolic pathways in each tissue and cell in our body. Each tissue has its own specific cytokines, but they cross-react to coordinate growth or deterioration throughout our whole body. The new word for skeletal muscle released cytokines associated with aerobic exercise is myokine.
 
                                                   
 
Science now suggests that good nutrition and physical exercise can create a moment-to-moment chemical balance between growth and deterioration within our muscles. These signals are then sent to the rest of our body via a series of interleukin proteins including interleukin-6 (IL-6) and interleudin-10 (IL-10), which are activated by the physical stress associated with regular aerobic exercise.                                                  

The inflammatory process associated with increased levels of stress activated pro-inflammatory proteins causes most cells in our bodies to deteriorate and fall apart after relatively short life spans. The good news is that this allows the human body to adapt to new environmental circumstances and it eliminates older cells that more easily become malignant. All forms of aerobic exercise produce pro-inflammatory proteins in logarithmic proportion to both the duration and intensity of exercise.

The master proteins for growth and repair, including anti-inflammatory IL-10, are produced in response to the level of  pro-inflammatory proteins, including IL-6. This is our body’s brilliant mechanism for balancing growth and deterioration.  If adequate antioxidants are available and enough of the protein growth signals are sent at once, they overwhelm the pro-inflammatory signals that activate cellular and tissue atrophy, and our bodies turn on specific metabolic processes to protect and build up the muscles, heart, capillaries, tendons, bones, joints, brain and eyes.
 
Inflammatory protein levels peak right after strenuous exercise. This peak signals the anti-inflammatory proteins to start cellular and tissue repair. Il-10 protein levels, as an example, peak an hour or so later and stay at fairly high levels for hours after hard exercise. And this happens at any age.
 
Not all deterioration is good however, and not all IL-6 triggers the production of IL-10. When we are sedentary, or only pretend to sort of exercise, there is a constant slow release of pro-inflammatory proteins, but not enough to switch on the growth and repair anti-inflammatory proteins.
 
Unfortunately, the aging process also causes a slow release of pro-inflammatory proteins that are below the level required to turn on, or stimulate, growth and repair proteins. Thereby explaining the silent inflammatory process associated with aging and also explaining why aerobic exercise becomes even more important after the age of 50.
 
Ellen Troyer, MT MA - Biosyntrx Chief Research Officer

PEARL

Proteomic science suggests that long term good health is a lifestyle choice, as well as an endurance event, so if you are not physically training for it at least an hour a day, four or preferably six days a week at appropriate target heart rates,  start now.
 
Target Heart Rate
 
Henry Lodge, MD, suggests in his book, Younger Next Year, that we subtract our age from 220 to identify our maximum target heart rate.  For example, if you are 60 years old your theoretical max heart rate would be around 160. Now take 60% of that number for long and slow daily exercise (your heart rate should stay around 96 beats per minute), 70% of that number for at least once a week high endurance exercise (112 beats per minute after you are in shape),  and 80% of that number for occasional short spurt anaerobic exercise (128 beats per minute).
 
Dr. Lodge cautions that all people should have a physical check-up before starting any exercise program.  He also recommends that those who are truly serious about exercising at target heart rates wear an inexpensive heart monitor for best results.  

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References

State of the Art Reviews: The Anti-Inflammatory Actions of Exercise Training. Flynn Michael. American Journal of Lifestyle Medicine  2007 Vol 1, No 3: 220-235 [abstract]
 
Physiological roles of muscle-derived interleukin-6 in response to exercise.  Pedersen BK, Fisher CP. Curr Opin Clin Nutr Metab Care 2007 May; 10(3):265-71 [abstract]
 
Beneficial health effects of exercise - the role of IL-6 as a myokine. Pedersen BK, Fisher CP Trends Pharmacol Sci 2007 Apr;28(4):152-154 [abstract]
 
Searching for the exercise factor: is IL-6 a candidate? Pedersen BK, Steensberg A, et al. J Muscle Res Cell Motil 2003;24(2-3):113-9 [abstract]
 
Pro-and anti-inflammatory cytokine balance in strenuous exercise in humans. Ostrowski K, Rohde T, et al.  J Physiol 1999 Feb 15;515: 287-91. [abstract]
 
Long-term exercise and atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease. Smith JK, Dykes R, et al. JAMA 1999;281:1722-1727 [abstract]
 
The Effect of Weight Loss on C-Reactive Protein. Selvin E, Paynter N, et al. Arch Intern Med 2007; 167:31-39 [abstract]
 
Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4. McFarlin, B, Flynn M, et al. The Journal of Gerontology 2006 61:388-393 [abstract]
 
The anti-inflammatory effect of exercise. Petersen A, Pedersen B, Journal of Applied Physiology. 2005 98: 1154-1162 [abstract]
 
Physical activity and the 15-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study.  Knudtson MD, Klein R, Klein BE. Br J Ophthalmol 2006 Dec;90(12):1461-3 [abstract]
 
Younger Nezxt Year. A guide to living like 50 until you're 80 and beyond.  Chris Crowley & Henry S. Lodge, MD. Workman Publishing New York. 2004  [amazon]