title: Senescence of human skeletal muscle impairs the local inflammatory cytokine response to acute eccentric exercise.
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 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-beta1) 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 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.
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Hamada
authors.forename: Edouard
authors.initials: E
authors.lastname: Vannier
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Sacheck
authors.forename: Alice L
authors.initials: AL
authors.lastname: Witsell
authors.forename: Ronenn
authors.initials: R
authors.lastname: Roubenoff
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000097:blood / Q000473:pathology* / Q000652:urine; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002097:C-Reactive Protein / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism / Q000652:urine; D007866:Leg / Q000473:pathology; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology*; D012420:Running / Q000502:physiology
chemical_list: D015415:Biomarkers; D018821:CD18 Antigens; D016207:Cytokines; D018076:DNA, Complementary; D002097:C-Reactive Protein