Nutritional strategies targeting age-related skeletal muscle fibrosis: underlying mechanisms

Aging is associated with a reduced number and function of muscle stem cells (MuSC). This results in a decreased muscle regenerative capacity and increased formation of fibrotic tissue, impairing skeletal muscle function. This review provides an overview of in vitro and in vivo animal studies investigating nutritional interventions with the potential to inhibit pathophysiological mechanisms involved in the development of skeletal muscle fibrosis. Mechanism targets include 1) MuSC function and myogenic differentiation, 2) M1 to M2 macrophage polarization, 3) myofibroblast activity or extracellular matrix (ECM) deposition, and 4) reactive oxygen species (ROS) mediated pathways, such as NOX2/4 activity. Most promising nutrients described in this review are phytonutrients, vitamins and amino acids. Quercetin targets multiple pathways (showing decreased inflammation, ECM expression and NOX2/4 activity) in various cell types and tissues (kidney, aorta, liver and (heart) muscle) of rodents and rabbits, which could contribute to fibrosis development. Additionally, sulforaphane is a promising candidate as it inhibits inflammation, ECM expression, and ROS production in mouse skeletal muscle. After validation of the effects in human skeletal muscle, supplementation with these nutrients could be implemented in a multifaceted intervention (including exercise and adequate protein intake) targeting age-related skeletal muscle fibrosis.