Senescence of human skeletal muscle impairs the local inflammatory cytokine response to acute eccentric exercise

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 years old, n = 15) and old (66-78 years old, 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-beta(1)) were quantified by real-time PCR. Before exercise, cytokine transcripts did not differ with age. At old age, exercise induced a blunted accumulation of transcripts encoding the panleukocyte 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-beta(1) 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.