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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #178796
Title: SENESCENCE OF HUMAN SKELETAL MUSCLE IMPAIRS THE LOCAL INFLAMMATORY CYTOKINE RESPONSE TO ACUTE ECCENTRIC EXERCISE

Author
item HAMADA, KOICHIRO - OTSUKA PHARMACEUTICALS
item VANNIER, EDOUARD - TUFTS/HNRCA
item SACHECK, JENNIFER - TUFTS UNIVERSITY
item WITSELL, ALICE - CONSULTANT
item ROUBENOFF, RONENN - MILLENNIUM PHARMACEUTICAL

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/12/2004
Publication Date: 2/1/2005
Citation: Hamada, K., Vannier, E., Sacheck, J., Witsell, A., Roubenoff, R. 2005. Senescence of human skeletal muscle impairs the local inflammatory cytokine response to acute eccentric exercise. Journal of Federation of American Societies for Experimental Biology. 19(2):264-266.

Interpretive Summary: An inflammatory reaction is necessary for the remodeling and adaptation of muscle tissue upon damaging exercise. The inflammatory reaction is orchestrated by an influx of white blood cells that, in conjunction with resident cells of the inflamed muscle tissue, release soluble proteins (cytokines) with inflammatory and anti-inflammatory properties. The impact of aging on the inflammatory reaction in the exercised muscle is poorly understood. We enrolled physically active young (23-35 years) and old (66-78 years) men to perform 45 minutes of downhill running (16% descent) at 75% of their individual maximal pace. Biopsies of the quadriceps muscle were obtained 24 hours before and 72 hours after the exercise. Prior to exercise, age did not affect basal expression of genes coding for the inflammatory (tumor necrosis factor and interleukin-1) and anti-inflammatory (interleukin-6 and transforming growth factor beta 1) cytokines. However, old age dramatically reduced gene expression for CD18, a surface marker found on all white blood cells. This observation suggests that there is a blunted recruitment of inflammatory cells in the exercised muscle of old individuals. Furthermore, old age nearly abolished the expression of the interleukin-6 gene that is otherwise induced by exercise in the young subjects. This effect is somewhat selective, since old age did not affect gene expression for the other cytokines tested. Our results suggest that aging impairs the adaptive response of human skeletal muscle to damaging exercise by differential modulation of a discrete set of inflammatory and anti-inflammatory cytokine genes.

Technical Abstract: The impact of aging on the cytokine response of human skeletal muscle to exercise-induced injury remains poorly understood. We enrolled physically active young (23-35 yr, n=15) and old (66-78 yr, n=15) men to perform 45 min of downhill running (16% descent) at 75% VO2max. Biopsies of vastus lateralis were obtained 24 h before and 72 h after acute eccentric exercise. Transcripts for inflammatory (TNF-alpha, IL-1beta) and anti-inflammatory cytokines (IL-6, TGF-beta1) were quantified by real-time PCR. Prior to exercise, cytokine transcripts did not differ with age. At old age, exercise induced a blunted accumulation of transcripts encoding the pan-leukocyte surface marker CD18 (young: 10.1 fold increase, P<0.005; old: 4.7 fold increase, P=0.02; young vs. old: P<0.05). In both age groups, CD18 transcript accumulation strongly correlated with TNF-alpha (young, r=0.87, P<0.001; old, r=0.72, P=0.002) and TGF-beta1 transcript accumulation (young, r=0.80, P<0.001; old, r=0.64, P=0.008). At old age, there was no correlation between IL-1beta and CD18 transcript accumulation. Furthermore, exercise induced IL-6 transcript accumulation in young (3.6 fold, P=0.057), but not in old men. Our results suggest that aging impairs the adaptive response of human skeletal muscle to eccentric exercise by differential modulation of a discrete set of inflammatory and anti-inflammatory cytokine genes.