Skeletal muscle as potential central link between sarcopenia and immune senescence

Abstract

As our population grows older, age-related pathologies are becoming more prevalent. Deterioration of skeletal muscle and the immune system manifests as sarcopenia and immune senescence respectively. The disease burden of these pathologies emphasizes the need for a better understanding of the underlying mechanisms. Skeletal muscle has emerged as a potent regulator of immune system function. As such, skeletal muscle might be the central integrator between sarcopenia and immune senescence in an aging biological system. Therapeutic approaches targeting skeletal muscle might be able to restore both muscle and immune system function. In this review, we therefore outline the current - however still fragmentary - knowledge about the potential communication pathways of muscle and immune system, how they are affected by aging of skeletal muscle and discuss possible treatment strategies. The review intends to be hypothesis-generating and should thereby stimulate further research in this important scientific field.

Keywords: IL-15; IL-6, IL-7; Immune senescence; Myokines; Sarcopenia; Skeletal muscle.

Fig. 1

Aging of skeletal muscle is central in the pathogenesis of immune senescence and sarcopenia. Multiple pathways are affected, including insufficient myokine signalling (IL-6, IL-7, IL-15), shifting of membrane bound immune regulatory factors towards a pro-inflammatory profile, impaired immune cell function and altered body composition.

Fig. 2

Aging tips the scales of IL-6 signalling. Chronic exposure to IL-6 and the concomitant release of pro-inflammatory cytokines promote pro-inflammatory effects and muscle catabolism due to IL-6 signalling. The pulsatile release of IL-6 in response to exercise is impaired in sarcopenia resulting in reduced anti-inflammatory effects and impaired muscle anabolism mediated by IL-6. The biological effect of IL-6 is mediated both by canonical and by trans-signalling.