Mapping mammalian biochemistry is a sizable task, and much of that biochemistry remains poorly understood and categorized. Cell signaling is a vast topic in and of itself. Here researchers discuss myokines, signal molecules generated by muscle cells as a result of exercise. These diverse signals are influential on tissue function and health, and mediate some fraction of the benefits resulting from physical activity. Further, some clearly change in abundance with age, and might therefore be useful targets for interventions intended to better maintain health and function with aging.

In recent decades, it has been discovered that contracting skeletal muscles release various hormone-like substances. These activators are called myokines, which are small proteins and proteoglycan peptides that are produced and secreted by skeletal muscle cells in response to muscle contractions. Various myokines secreted by skeletal muscles during aerobic and anaerobic exercises have been studied in connection with various human diseases. For a long time, skeletal muscles were only recognized as being involved in the physical aspects of exercise. However, with the discovery of exercise-induced myokines, skeletal muscles have been demonstrated to be involved in the maintenance of metabolic homeostasis. Although the detailed mechanisms are not clear, both skeletal muscle contraction and mass maintenance appear to be actively involved in maintaining health and preventing disease development in the elderly, particularly considering the rapid deterioration of muscle physiology with aging.

This review summarizes 13 myokines regulated by physical activity that are affected by aging and aims to understand their potential roles in metabolic diseases. We categorized myokines into two groups based on regulation by aerobic and anaerobic exercise. With aging, the secretion of apelin, β-aminoisobutyric acid (BAIBA), bone morphogenetic protein 7 (BMP-7), decorin, insulin-like growth factor 1 (IGF-1), interleukin-15 (IL-15), irisin, stromal cell-derived factor 1 (SDF-1), sestrin, secreted protein acidic rich in cysteine (SPARC), and vascular endothelial growth factor A (VEGF-A) decreased, while that of IL-6 and myostatin increased. Aerobic exercise upregulates apelin, BAIBA, IL-15, IL-6, irisin, SDF-1, sestrin, SPARC, and VEGF-A expression, while anaerobic exercise upregulates BMP-7, decorin, IGF-1, IL-15, IL-6, irisin, and VEGF-A expression. Myostatin is downregulated by both aerobic and anaerobic exercise.

Although the 13 myokines reviewed are all stimulated by exercise, each has unique characteristics. In brief, apelin is an anti-aging factor and has positive effects on hypertension and ischemia-reperfusion injury when combined with exercise. BAIBA prevents metabolic diseases by acting as an osteocyte survival factor, protecting against mitochondrial breakdown, and attenuating bone and skeletal muscle loss. BMP-7 is an important factor in bone formation and skeletal muscle mass maintenance. Decorin, IGF-1, and SDF-1 have positive effects on tendon strength, bone and tissue development, and skeletal muscle regeneration, respectively. IL-15 facilitates fibroblast collagen synthesis and cell proliferation. IL-6 contributes to the maintenance of glucose homeostasis, obesity regulation, microglial function, and lactate production. Irisin might become a treatment for Alzheimer’s disease because of its positive influence on neuron functional impairment. The most interesting is myostatin. Unlike the other myokines, exercise reduces its secretion. It is beneficial in chronic heart failure, chronic kidney disease, and lipidomic abnormalities. Sestrin helps prevent the development of age-associated metabolic diseases and sarcopenia. SPARC, which is increased by aerobic exercise, has potential as a cancer treatment. VEGF-A, which is upregulated by both anaerobic and aerobic exercise, is involved in the growth and survival of skeletal muscle.

The biggest takeaway of our review is that both aerobic and anaerobic exercises exert positive effects on skeletal muscles by releasing various myokines that are beneficial to the elderly. Given that most studies on long term physical activity in the elderly have focused on aerobic exercises, it is worth broadening the scope of research by examining the need for anaerobic exercise.