Skeletal Muscle Extracellular Matrix – What Do We Know About Its Composition, Regulation, and Physiological Roles? A Narrative Review

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Copyright © 2013 Elsevier Inc. All rights reserved.

The purpose of this Position Stand is to provide guidance to professionals who counsel and prescribe individualized exercise to apparently healthy adults of all ages. These recommendations also may apply to adults with certain chronic diseases or disabilities, when appropriately evaluated and advised by a health professional. This document supersedes the 1998 American College of Sports Medicine (ACSM) Position Stand, "The Recommended Quantity and Quality of Exercise for Developing and Maintaining Cardiorespiratory and Muscular Fitness, and Flexibility in Healthy Adults." The scientific evidence demonstrating the beneficial effects of exercise is indisputable, and the benefits of exercise far outweigh the risks in most adults. A program of regular exercise that includes cardiorespiratory, resistance, flexibility, and neuromotor exercise training beyond activities of daily living to improve and maintain physical fitness and health is essential for most adults. The ACSM recommends that most adults engage in moderate-intensity cardiorespiratory exercise training for ≥30 min·d on ≥5 d·wk for a total of ≥150 min·wk, vigorous-intensity cardiorespiratory exercise training for ≥20 min·d on ≥3 d·wk (≥75 min·wk), or a combination of moderate- and vigorous-intensity exercise to achieve a total energy expenditure of ≥500-1000 MET·min·wk. On 2-3 d·wk, adults should also perform resistance exercises for each of the major muscle groups, and neuromotor exercise involving balance, agility, and coordination. Crucial to maintaining joint range of movement, completing a series of flexibility exercises for each the major muscle-tendon groups (a total of 60 s per exercise) on ≥2 d·wk is recommended. The exercise program should be modified according to an individual's habitual physical activity, physical function, health status, exercise responses, and stated goals. Adults who are unable or unwilling to meet the exercise targets outlined here still can benefit from engaging in amounts of exercise less than recommended. In addition to exercising regularly, there are health benefits in concurrently reducing total time engaged in sedentary pursuits and also by interspersing frequent, short bouts of standing and physical activity between periods of sedentary activity, even in physically active adults. Behaviorally based exercise interventions, the use of behavior change strategies, supervision by an experienced fitness instructor, and exercise that is pleasant and enjoyable can improve adoption and adherence to prescribed exercise programs. Educating adults about and screening for signs and symptoms of CHD and gradual progression of exercise intensity and volume may reduce the risks of exercise. Consultations with a medical professional and diagnostic exercise testing for CHD are useful when clinically indicated but are not recommended for universal screening to enhance the safety of exercise.

During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines. The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some myokines exert their effects within the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal L cells and pancreatic islets. Other myokines include the osteogenic factors IGF-1 and FGF-2; FSTL-1, which improves the endothelial function of the vascular system; and the PGC-1α-dependent myokine irisin, which drives brown-fat-like development. Studies in the past few years suggest the existence of yet unidentified factors, secreted from muscle cells, which may influence cancer cell growth and pancreas function. Many proteins produced by skeletal muscle are dependent upon contraction; therefore, physical inactivity probably leads to an altered myokine response, which could provide a potential mechanism for the association between sedentary behaviour and many chronic diseases.