Muscle function reflects muscular mitochondrial status, which, in turn, is an adaptive response to physical activity, representing improvements in energy production for de novo biosynthesis or metabolic efficiency. Differences in muscle performance are manifestations of the expression of distinct contractile-protein isoforms and of mitochondrial-energy substrate utilization. Powerful contractures require immediate energy production from carbohydrates outside the mitochondria that exhaust rapidly. Sustained muscle contractions require aerobic energy production from fatty acids by the mitochondria that is slower and produces less force. These two patterns of muscle force generation are broadly classified as glycolytic or oxidative, respectively, and require disparate levels of increased contractile or mitochondrial protein production, respectively, to be effectively executed. Glycolytic muscle, hence, tends towards fibre hypertrophy, whereas oxidative fibres are more disposed towards increased mitochondrial content and efficiency, rather than hypertrophy. Although developmentally predetermined muscle classes exist, a degree of functional plasticity persists across all muscles post-birth that can be modulated by exercise and generally results in an increase in the oxidative character of muscle. Oxidative muscle is most strongly correlated with organismal metabolic balance and longevity because of the propensity of oxidative muscle for fatty-acid oxidation and associated anti-inflammatory ramifications which occur at the expense of glycolytic-muscle development and hypertrophy. This muscle-class size disparity is often at odds with common expectations that muscle mass should scale positively with improved health and longevity. Brief magnetic-field activation of the muscle mitochondrial pool has been shown to recapitulate key aspects of the oxidative-muscle phenotype with similar metabolic hallmarks. This review discusses the common genetic cascades invoked by endurance exercise and magnetic-field therapy and the potential physiological differences with regards to human health and longevity. Future human studies examining the physiological consequences of magnetic-field therapy are warranted.

Briefly (10 min) exposing C2C12 myotubes to low amplitude (1.5 mT) pulsed electromagnetic fields (PEMFs) generated a conditioned media (pCM) that was capable of mitigating breast cancer cell growth, migration, and invasiveness in vitro, whereas the conditioned media harvested from unexposed myotubes, representing constitutively released secretome (cCM), was less effective. Administering pCM to breast cancer microtumors engrafted onto the chorioallantoic membrane of chicken eggs reduced tumor volume and vascularity. Blood serum collected from PEMF-exposed or exercised mice allayed breast cancer cell growth, migration, and invasiveness. A secretome preconditioning methodology is presented that accentuates the graded anticancer potencies of both the cCM and pCM harvested from myotubes, demonstrating an adaptive response to pCM administered during early myogenesis that emulated secretome-based exercise adaptations observed in vivo. HTRA1 was shown to be upregulated in pCM and was demonstrated to be necessary and sufficient for the anticancer potency of the pCM; recombinant HTRA1 added to basal media recapitulated the anticancer effects of pCM and antibody-based absorption of HTRA1 from pCM precluded its anticancer effects. Brief and non-invasive PEMF stimulation may represent a method to commandeer the secretome response of muscle, both in vitro and in vivo, for clinical exploitation in breast and other cancers.

The cryptochromes are flavoproteins that either individually or synergistically respond to light and magnetic field directionality as well as are implicated in circadian rhythm entrainment and development. Single brief exposures (10 min) to low energy (1.5 mT) pulsed electromagnetic fields (PEMFs) were previously shown to enhance myogenesis by stimulating transient receptor potential canonical 1 (TRPC1)-mediated Ca²⁺ entry, whereby downwardly directed fields produced greater myogenic enhancement than upwardly directed fields. Here, we show that growth in the dark results in myoblasts losing their sensitivity to both magnetic field exposure and directionality. By contrast, overexpressing or silencing cryptochrome circadian regulator 2 (CRY2) in myoblasts enhances or reduces PEMF responses, respectively, under conditions of ambient light. Reducing cellular flavin adenine dinucleotide (FAD) content by silencing riboflavin kinase (RFK) attenuated responsiveness to PEMFs and inhibited selectivity for magnetic field direction. The upregulation of TRPC1 and cell cycle regulatory proteins typically observed in response to PEMF exposure was instead attenuated by upwardly directed magnetic fields, growth in the darkness, magnetic shielding, or the silencing of CRY2 or RFK. A physical interaction between CRY2 and TRPC1 was detected using coimmunoprecipitation and immunofluorescence, revealing their co-translocation into the nucleus after PEMF exposure. These results implicate CRY2 in an identified TRPC1-dependent magnetotransduction myogenic cascade.

This study compared the metabolic consequences of fecal microbiota transplantation (FMT) from donor mice that had been either administered pulsed electromagnetic field (PEMF) therapy or exercised to recipient mice fed a high-fat diet (HFD). Eight weeks of PEMF treatment (10 min/week) enhanced PGC-1α-associated mitochondrial and metabolic gene expression in white and brown adipose to a greater degree than eight weeks of exercise (30–40 min/week). FMT from PEMF-treated donor mice recapitulated these adipogenic adaptations in HFD-fed recipient mice more faithfully than FMT from exercised donors. Direct PEMF treatment altered hepatic phospholipid composition, reducing long-chain ceramides (C16:0) and increasing very long-chain ceramides (C24:0), which could be transferred to PEMF-FMT recipient mice. FMT from PEMF-treated mice was also more effective at recovering glucose tolerance than FMT from exercised mice. PEMF treatment also enhanced bone density in both donor and HFD recipient mice. The gut Firmicutes/Bacteroidetes (F/B) ratio was lowest in both the directly PEMF-exposed and PEMF-FMT recipient mouse groups, consistent with a leaner phenotype. PEMF treatment, either directly applied or via FMT, enhanced adipose thermogenesis, ceramide levels, bone density, hepatic lipids, F/B ratio, and inflammatory blood biomarkers more than exercise. PEMF therapy may represent a non-invasive and non-strenuous method to ameliorate metabolic disorders.