Recent advances and future avenues in understanding the role of adipose tissue cross talk in mediating skeletal muscle mass and function with ageing

Abstract

Sarcopenia, broadly defined as the age-related decline in skeletal muscle mass, quality, and function, is associated with chronic low-grade inflammation and an increased likelihood of adverse health outcomes. The regulation of skeletal muscle mass with ageing is complex and necessitates a delicate balance between muscle protein synthesis and degradation. The secretion and transfer of cytokines, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), both discretely and within extracellular vesicles, have emerged as important communication channels between tissues. Some of these factors have been implicated in regulating skeletal muscle mass, function, and pathologies and may be perturbed by excessive adiposity. Indeed, adipose tissue participates in a broad spectrum of inter-organ communication and obesity promotes the accumulation of macrophages, cellular senescence, and the production and secretion of pro-inflammatory factors. Pertinently, age-related sarcopenia has been reported to be more prevalent in obesity; however, such effects are confounded by comorbidities and physical activity level. In this review, we provide evidence that adiposity may exacerbate age-related sarcopenia and outline some emerging concepts of adipose-skeletal muscle communication including the secretion and processing of novel myokines and adipokines and the role of extracellular vesicles in mediating inter-tissue cross talk via lncRNAs and miRNAs in the context of sarcopenia, ageing, and obesity. Further research using advances in proteomics, transcriptomics, and techniques to investigate extracellular vesicles, with an emphasis on translational, longitudinal human studies, is required to better understand the physiological significance of these factors, the impact of obesity upon them, and their potential as therapeutic targets in combating muscle wasting.

eNAMPT Is Localised to Areas of Cartilage Damage in Patients with Hip Osteoarthritis and Promotes Cartilage Catabolism and Inflammation

“…Importantly, obesity is a risk factor for OA, but the relationship between obesity and OA may not simply be due to weight-related increased loading on the joint, since BMI is also associated with the development of OA in non-weight-bearing joints, such as the hands [3,4]. One group of proteins that provide a link between obesity and joint damage are the adipose-secreted cytokines (adipokines), which are known regulators of metabolism [5][6][7][8][9][10] and the inflammatory response [11][12][13][14][15][16][17][18].…”

Adipose-Secreted Exosomes and Their Pathophysiologic Effects on Skeletal Muscle

“…Knowledge about developmental biology suggests the growth of skeletal muscle preceding that of AT; however, with age the growth speed of AT increases, while that of skeletal muscle decreases [ 50 ]. The relative proportion of these different tissues is regulated throughout life, and changes in their proportion at different developmental stages may affect relevant metabolic regulation, contributing the occurrence of disease.…”

“…Because of expanding capacity of adipocytes in animal tissues, ectopic intermuscular lipid deposition is frequently observed within the perimysium of skeletal muscles, which become disorganized and remodeled as adipocytes mature [ 96 ]. In vitro studies have suggested that perimuscular lipid deposition accelerates aging-induced muscle atrophy factor-related proteolysis and muscle senescence, and induces progressive loss of skeletal muscle mass and function [ 50 , 97 ]. Moreover, the lipid deposition in skeletal muscle can also induce a shift from type II fibers to a type I phenotype, leading to impaired muscle contractility of both type I and type II fibers, resulting in a dramatic decrease in muscle strength [ 98 ].…”

Muscle and Adipose Tissue Communicate with Extracellular Vesicles

“…Knowledge about tissue growth suggests prioritization or a competition for the growth of muscles compared to that of adipose tissue. Indeed, the growth of muscle precedes that of adipose tissue, and growth allometric analysis shows that the growth speed of adipose tissue increases with age, while that of muscle decreases [4]. The relative proportion of these different tissues is regulated throughout life, and the alteration of this ratio, either during the prenatal stage or after birth, impairs the control of body weight and fasting glycemia, and it can contribute to diabetes and cardiovascular diseases.…”