Exercise mimetics: molecular mechanisms, biological and therapeutic effects
4 affiliations
- 1Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University (NMU), Shanghai, China
- 2Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University (NMU), Shanghai, China. [email protected]
- 3Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University (NMU), Shanghai, China. [email protected]
- 4Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University (NMU), Shanghai, China. [email protected]
Abstract
Accumulating evidence underscores the therapeutic benefits of exercise in the prevention and treatment of various diseases. However, many patients are unable to engage in sufficient physical training because of frailty, disability, or disease burden. This challenge has stimulated considerable interest in exercise mimetics, which are pharmacological or biological interventions designed to activate exercise-responsive pathways and recapitulate the key adaptive responses elicited by physical activity. In this Review, we outline the conceptual foundations, classification, historical evolution, and biological rationale of exercise mimetics, and organize the field according to its major mechanisms, including neurotrophic signaling, redox regulation, immune modulation, mechanotransduction, vascular coupling, mitochondrial metabolism, epigenetic remodeling, and inter-organ crosstalk. We further examine how these pathways shape normal physiology and development, with an emphasis on metabolic homeostasis, neurodevelopment, cognition, aging, angiogenesis, and inflammation. Building on this framework, we evaluate emerging applications in major human diseases, including cancer, traumatic injury, cardiovascular disorders, neurodegenerative disorders, and inflammatory or immune-mediated conditions, with particular attention to neuroregeneration and systems-level repair. Finally, we assess clinical and translational advances in biomarker-guided diagnosis, personalized treatment, circulating mediators, drug delivery, combination therapy, and clinical trials. Although exercise mimetics offer a scalable and mechanism-informed therapeutic strategy, most evidence to date remains preclinical, and substantial challenges related to pharmacokinetics, safety, target engagement, and patient heterogeneity must be overcome before clinical implementation.
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BibTeX
@article{zhang2026exercise,
title = {{Exercise mimetics: molecular mechanisms, biological and therapeutic effects}},
author = {J. Zhang and Qi Shao and 程腾 and Junjian Lin and Yiqin Tang and Haodong Lu and Yue Zhang and Zhongwang Yu and Li Cao},
journal = {Molecular Biomedicine},
year = {2026},
month = jun,
doi = {10.1186/s43556-026-00483-8},
url = {https://doi.org/10.1186/s43556-026-00483-8},
note = {CC BY},
}
RIS
TY - JOUR
TI - Exercise mimetics: molecular mechanisms, biological and therapeutic effects
AU - J. Zhang
AU - Qi Shao
AU - 程腾
AU - Junjian Lin
AU - Yiqin Tang
AU - Haodong Lu
AU - Yue Zhang
AU - Zhongwang Yu
AU - Li Cao
PY - 2026
DA - 2026/06/03
JO - Molecular Biomedicine
DO - 10.1186/s43556-026-00483-8
UR - https://doi.org/10.1186/s43556-026-00483-8
AB - Accumulating evidence underscores the therapeutic benefits of exercise in the prevention and treatment of various diseases. However, many patients are unable to engage in sufficient physical training because of frailty, disability, or disease burden. This challenge has stimulated considerable interest in exercise mimetics, which are pharmacological or biological interventions designed to activate exercise-responsive pathways and recapitulate the key adaptive responses elicited by physical activity. In this Review, we outline the conceptual foundations, classification, historical evolution, and biological rationale of exercise mimetics, and organize the field according to its major mechanisms, including neurotrophic signaling, redox regulation, immune modulation, mechanotransduction, vascular coupling, mitochondrial metabolism, epigenetic remodeling, and inter-organ crosstalk. We further examine how these pathways shape normal physiology and development, with an emphasis on metabolic homeostasis, neurodevelopment, cognition, aging, angiogenesis, and inflammation. Building on this framework, we evaluate emerging applications in major human diseases, including cancer, traumatic injury, cardiovascular disorders, neurodegenerative disorders, and inflammatory or immune-mediated conditions, with particular attention to neuroregeneration and systems-level repair. Finally, we assess clinical and translational advances in biomarker-guided diagnosis, personalized treatment, circulating mediators, drug delivery, combination therapy, and clinical trials. Although exercise mimetics offer a scalable and mechanism-informed therapeutic strategy, most evidence to date remains preclinical, and substantial challenges related to pharmacokinetics, safety, target engagement, and patient heterogeneity must be overcome before clinical implementation.
SN - 2662-8651
ER -