Reviewing What is Known of Exerkines
An exerkine is a signaling molecule secreted in response to exercise. Classifying signaling in this way is a fairly recent development, and so mapping the space of exerkines is an ongoing exercise. Myokines, signal molecules released by muscle, are another recently established category, and there is some overlap between exerkines and myokines. Exerkines are a broader category, and might in principle be produced in any tissue in response to exercise. Evidently regular exercise is beneficial, and the goal of exerkine research is to better understand how those benefits are produced, potentially with the goal of producing exercise mimetic drugs.
Exerkines are bioactive molecules released by various tissues in response to exercise and are essential mediators in the anti-aging effects of physical activity. Initially, it was believed that exerkines were primarily produced by skeletal muscle, but recent studies have shown that multiple organs, including the liver, adipose tissue, bone, and the nervous system, also secrete these molecules. These exerkines not only act locally but also exert systemic effects across the body, regulating metabolic processes, reducing inflammation, supporting tissue repair, and maintaining cognitive function.
The release of exerkines is a highly coordinated process that involves multiple tissues and organs. These exerkines function in a synergistic manner to combat the cellular and molecular changes associated with aging, such as oxidative stress, inflammation, mitochondrial dysfunction, and tissue degeneration. By enhancing the production of these molecules, regular exercise creates an environment that promotes tissue maintenance, metabolic balance, cardiovascular health, and cognitive resilience. This highlights the central role of exerkines in the anti-aging benefits of exercise, as they help to preserve functional capacity and overall health as we age.
Exercise promotes the release of exerkines such as IGF-1, GPLD1, BDNF, clusterin, and PF4, leading to enhanced synaptic plasticity, improved neuroprotection, and reduced neuroinflammation. The upregulation of PGC-1α in response to exercise contributes to cardiomyocyte hypertrophy, increased proliferation, and anti-apoptotic effects, which support overall cardiac health and longevity. Exercise decreases hepatic steatosis and modulates the inflammatory response via the increased secretion of IL-10 and irisin, reducing liver inflammation and improving metabolic homeostasis. Exerkines like FGF-21 and apelin stimulate lipid oxidation, decrease fat mass, and promote the browning of adipose tissue, contributing to improved metabolic function and fat utilization. NOX4 and HSP90 are upregulated during exercise, improving muscular contractility, and enhancing the antioxidant capacity of mitochondria, thereby reducing oxidative stress.