Magnetic fields as biophysical activators of autophagy: A preclinical systematic review

While pharmacological inducers of autophagy have been extensively studied, their systemic adverse effects may limit clinical use. Increasing preclinical evidence suggests that magnetic fields (MFs) can represent a non-invasive alternative for autophagy modulation. In this systematic review, we sought to evaluate preclinical evidence on MF-mediated autophagy activation, including intervention parameters, mechanistic pathways, and therapeutic outcomes, to guide future translational research. Following PRISMA guidelines, we searched (January 2010-August 2025) four structured electronic databases (PubMed, Scopus, Embase, and IEEE Xplore) for studies investigating MF effects on autophagy in preclinical models. Eligible reports included in vitro and animal investigations with clearly defined MF parameters and validated autophagy markers. Nine studies met inclusion criteria, covering diverse MF modalities such as repetitive transcranial magnetic stimulation, rotating fields, pulsed and power-frequency fields, and radiofrequency exposures. Across a wide range of frequencies (1-50 Hz) and intensities (20 mT-1.5 T), most studies reported autophagy activation, as evidenced by LC3-II accumulation, Beclin-1 upregulation, p62 degradation, and autophagic flux confirmation in select experimental models. Mechanistic analyses converged on PI3K/AKT/mTOR inhibition. Functionally, MF-induced autophagy conferred neuronal protection and drove behavioral recovery in models of Alzheimer's disease, vascular dementia, and stress, whereas it triggered autophagic cell death in cancer. Some studies reported incomplete flux or autophagosome accumulation. Risk of bias was generally unclear due to methodological heterogeneity. In summary, preclinical evidence indicates that MFs can act as versatile, non-pharmacological activators of autophagy. Defining optimal stimulation parameters, clarifying mechanistic pathways, and advancing translational studies will be essential for clinical application.