Effects of exercise on exosome release and cargo in in vivo and ex vivo models: A systematic review

Abstract

Exercise‐released exosomes have been identified as novel players to mediate cell‐to‐cell communication in promoting systemic beneficial effects. This review aimed to systematically investigate the effects of exercise on exosome release and cargo, as well as provide an overview of their physiological implications. Among the 436 articles obtained in the database search (WOS, Scopus, and PubMed), 19 articles were included based on eligibility criteria. Results indicate that exercise promotes the release of exosomes without modification of its vesicle size. The literature has primarily shown an exercise‐driven increase in exosome markers (Alix, CD63, CD81, and Flot‐1), along with other exosome‐carried proteins, into circulation. However, exosome isolation, characterization, and phenotyping methodology, as well as timing of sample recovery following exercise can influence the analysis and interpretation of findings. Moreover, a large number of exosome‐carried microRNAs (miRNAs), including miR‐1, miR‐133a, miR‐133b, miR‐206, and miR‐486, in response to exercise are involved in the modulation of proliferation and differentiation of skeletal muscle tissue, although antigen‐presenting cells, leukocytes, endothelial cells, and platelets are the main sources of exosome release into the circulation. Collectively, with the physiological implications as evidenced by the ex vivo trials, the release of exercise‐promoted exosomes and their cargo could provide the potential therapeutic applications via the role of intercellular communication.

Physical Activity as a Preventive Lifestyle Intervention Acts Through Specific Exosomal miRNA Species—Evidence From Human Short- and Long-Term Pilot Studies

“…Regular exercise has been known as a major intervention tool not only to attenuate the risk of a multitude of disorders from metabolic disease and neurodegenerative disorders to cancer, but also to delay the occurrence of numerous age-related diseases ( Brahmer et al, 2019 ). While most molecular mechanisms mediating the long-term beneficial effects of exercise remain unexplored, growing evidence suggests the involvement of tissue crosstalk via the release of exosomes following exercise ( Frühbeis et al, 2015 ; Estébanez et al, 2021 ). Exosomes are small extracellular vesicles (sEVs) (30–150 nm) that are secreted by fusion of multivesicular bodies to the plasma membrane ( Brennan et al, 2020 ).…”

Resistance Training Diminishes the Expression of Exosome CD63 Protein without Modification of Plasma miR-146a-5p and cfDNA in the Elderly

“…While the mechanisms of these age-mediated EVs changes still remains to be elucidated, muscle-derived exosomes can use both paracrine and endocrine signaling to alter muscle homeostasis and communicate with other tissues, respectively [ 55 ]. Our systematic review has recently provided the scientific evidence regarding the effects of acute and chronic exercise on exosome biology [ 56 ]. In general, the literature has shown an increase in exosome release, regardless of exercise protocols, in different animal [ 24 , 26 , 29 , 31 ] and human [ 24 , 28 , 30 ] research.…”

“…With limited literature examining the effects of exercise training in humans, our 8-week resistance training showed an attenuation of CD63 expression in trained subjects compared to the controls, whereas the expression of CD63 was increased in response to acute cycling exercise in young adults [ 58 ]. In animal studies, the majority of acute bouts of exercise [ 31 ] or short-term training (3-week swimming [ 24 ] and 2-week running [ 21 ]) elicited an increase in exosome markers (CD63, CD81, and Flot-1), regardless of the methods of isolation, characterization and phenotyping methodology, and exercise protocols (reviewed in [ 56 ]). The current literature has not provided sufficient evidence that healthy elderly subjects would have a large variation of CD63 response in such a short period of time.…”

Exosomes in atherosclerosis: performers, bystanders, biomarkers, and therapeutic targets

“…The healthy state of muscle is inextricably linked to regular physical activity, which helps reduce the risk of sedentary lifestyle-induced chronic cardiovascular diseases such as atherosclerosis 188 . Collectively, muscle-derived circulating exosomes play crucial roles in atherosclerosis 189 . Studies profiling changes in circulating exosomes associated with atherosclerosis-related metabolic abnormalities, as well as identifying their mechanisms, would be highly valuable.…”