Circulating Interleukin-6 Is Associated with Skeletal Muscle Strength, Quality, and Functional Adaptation with Exercise Training in Mobility-Limited Older Adults

G.J Grosicki, B.B. Barrett, D.A. Englund, C. Liu, T.G. Travison, T. Cederholm, A. Koochek, Å. von Berens, T.Gustafsson, T. Benard, K.F. Reid, R.A. Fielding

J Frailty Aging. 2020;9(1):57-63. doi: 10.14283/jfa.2019.30.

Human aging is characterized by a chronic, low-grade inflammation suspected to contribute to reductions in skeletal muscle size, strength, and function. Inflammatory cytokines, such as interleukin-6 (IL-6), may play a role in the reduced skeletal muscle adaptive response seen in older individuals.

The aim was to investigate relationships between circulating IL-6, skeletal muscle health and exercise adaptation in mobility-limited older adults.

99 mobility-limited (Short Physical Performance Battery (SPPB) ≤9) older adults were enrolled in this randomized controlled trial at the Exercise laboratory on the Health Sciences campus of an urban university.

The trial was characterized by a 6-month structured physical activity with or without a protein and vitamin D nutritional supplement.

Circulating IL-6, skeletal muscle size, composition (percent normal density muscle tissue), strength, power, and specific force (strength/CSA) as well as physical function (gait speed, stair climb time, SPPB-score) were measured pre- and post-intervention.

At baseline, Spearman's correlations demonstrated an inverse relationship (P<0.05) between circulating IL-6 and thigh muscle composition (r = -0.201), strength (r = -0.311), power (r = -0.210), and specific force (r = -0.248), and positive association between IL-6 and stair climb time (r = 0.256; P<0.05). Although the training program did not affect circulating IL-6 levels (P=0.69), reductions in IL-6 were associated with gait speed improvements (r = -0.487; P<0.05) in "higher" IL-6 individuals (>1.36 pg/ml). Moreover, baseline IL-6 was inversely associated (P<0.05) with gains in appendicular lean mass and improvements in SPPB score (r = -0.211 and -0.237, respectively).  

Comment:  These findings implicate age-related increases in circulating IL-6 as an important contributor to declines in skeletal muscle strength, quality, function, and training-mediated adaptation. Given the pervasive nature of inflammation among older adults, novel therapeutic strategies to reduce IL-6 as a means of preserving skeletal muscle health are enticing.