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.

Aging alters gene expression of growth and remodeling factors in human skeletal muscle both at rest and in response to acute resistance exercise

“…At rest, elderly muscle compared with young at least tended to possess significantly fewer macrophages even though whole muscle of the elderly contained significantly higher mRNA levels for the cytokines IL-1␤ and IL-10. Postexercise, functional markers indicated that macrophages were activated and cytokine expression increased, but these responses were exclusive to the young group, which is consistent with another report (29). These results suggest that decreased macrophage numbers and increased cytokine levels even in healthy elderly may be detrimental to resting muscle and diminish the functional response to exercise.…”

Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats

“…The decrease in body weight in arthritic rats can be seen in the decrease in skeletal muscle weight and in the adipose mass. This muscular atrophy has been reported in adjuvant-arthritic rats (Hamada et al 2000), septic rats (Cooney et al 1999) and rats treated with TNF (Hoshino et al 1991). In TNF-infused rats, the loss of gastrocnemius mass has been ascribed to food intake reduction (Hoshino et al 1991).…”

Modifying muscle mass – the endocrine perspective

“…Following 45-min downhill running at 75% VO 2max muscle interleukin (IL)-6 and transforming growth factor (TGF)-b1 concentrations did not increase in older (nZ15) as much as in younger subjects (nZ15; Carlson et al 1999, Hamada et al 2005, Carlson et al 1999. These differences could reflect alterations in the adaptive cytokine response within the muscle -increasingly evidence points to a role for locally generated IL-6 in assisting with satellite cell proliferation during muscle regeneration following injury (Toumi et al 2006).…”