REVIEW article
Front. Cell Dev. Biol.
Sec. Membrane Traffic and Organelle Dynamics
Exerkine-Loaded Exosomes in Muscle Aging: A Nexus of Exercise, Regeneration, and Crosstalk
Provisionally accepted
- 1Beijing Normal University, Beijing, China
- 2Zhangjiakou Vocational and Technical College, Zhangjiakou, China
- 3Beijing Sport University School of Sports Science, Beijing, China
- 4Hebei University of Engineering, Handan, China
- 5Affiliated Hospital of Hebei Engineering University, Clinical Medical College, Hebei University of Engineering, Handan 056002 Hebei, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
This review examines the critical role of extracellular vesicles, specifically exosomes, as mediators of intercellular and inter-organ communication in the context of skeletal muscle aging and regeneration. Skeletal muscle, traditionally viewed as a simple contractile tissue, is now recognized as a potent endocrine organ that secretes a diverse array of signaling molecules, collectively termed "exerkines," in response to physical activity. We integrate contemporary evidence demonstrating how exercise modulates the release and molecular composition of muscle-derived exosomes, which in turn influence key cellular processes. The report details how exosomal cargo, including non-coding RNAs and proteins, regulates muscle stem cell activation and differentiation, counteracts age-related decline (sarcopenia) by modulating protein homeostasis and inflammation, and facilitates systemic metabolic crosstalk with distant tissues such as adipose tissue. We also critically discuss the burgeoning therapeutic potential of engineered exosomes for musculoskeletal health, while highlighting significant and interconnected challenges in the field, including the lack of standardized methodologies and regulatory frameworks. This review provides a nuanced perspective on the "exerkine" hypothesis, underscoring the potential of exercise-modulated exosomes as both diagnostic biomarkers and novel therapeutic agents for maintaining lifelong muscle health.
Keywords: Exercise, Exerkines, Exosomes, muscle aging, Regeneration
Received: 16 Sep 2025; Accepted: 04 Feb 2026.
Copyright: © 2026 Li, Wu, Wang, Ding and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jinpeng He
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.