BACKGROUNDAge-associated decrease in type IIA/B human skeletal muscle fibers was detected in human biopsies in our previous study. The relationship between change in muscle fiber typing and bone mineral density (BMD) is, however, unknown either cross-sectionally or longitudinally. We therefore conducted a cross-sectional study to investigate their correlation using human muscle biopsies.

METHODSForty human subjects aged (53.4 ± 20.2) years were recruited. Histomorphometric parameters of their muscle biopsies were measured by ATPase staining and image analysis, including average area percentage, fiber number percentage, mean fiber area, and area percentage of connective tissues. Hip and spine BMD was measured by dual-energy X-ray absorptiometry. Partial correlation with adjusting age was performed.

RESULTSType IIB muscle fiber was found positively correlated with hip BMD irrespective to age and demonstrated significantly stronger relationship with BMD among all fiber types, in terms of its cross-sectional area (r = 0.380, P = 0.029) and size (r = 0.389, P = 0.025). Type IIA muscle fibers associated with hip BMD in mean fiber area only (r = 0.420, P = 0.015).

CONCLUSIONSType IIB muscle fiber may play an important role in maintaining bone quality. This may also be a relatively more sensitive fiber type of sarcopenia and osteoporosis. These findings further consolidate the muscle-bone relationship.

Adult ; Age Factors ; Aged ; Aged, 80 and over ; Bone Density ; physiology ; Female ; Humans ; In Vitro Techniques ; Male ; Middle Aged ; Muscle Fibers, Fast-Twitch ; cytology ; metabolism ; Prospective Studies ; Young Adult

Positive-sense RNA viruses modify intracellular calcium stores, endoplasmic reticulum and Golgi apparatus (Golgi) to generate membranous replication organelles known as viral factories. Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity. Here, we identified the vital role of a broad-spectrum antiviral, peruvoside in limiting the formation of viral factories. Mechanistically, we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) phosphorylation and Golgi vesiculation by peruvoside treatment. The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation. Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337 (T1337). We also showed 100% of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum. These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside, host-directed antivirals for positive-sense RNA virus-mediated disease, in the interim where no vaccine is available.