Toward countering muscle and bone loss with spaceflight: GSK3 as a potential target

• DOI: 10.1016/j.isci.2023.107047
• Publication Date: 2023-06-08T03:09:38Z
• Authors: Ryan W. Baranowski; Jessica L. Braun; Briana L. Hockey; Jenalyn L. Yumol; Mia S. Geromella; Colton J.F. Watson; Nigel Kurgan; Holt N. Messner; Kennedy C. Whitley; Adam J. MacNeil; Guillemette Gauqu...; Fabrice Bertile; William Gittings; Rene Vandenboom; Wendy E. Ward; Val A. Fajardo
• Keywords: Spaceflight; GSK3B; Hindlimb

We examined the effects of ∼30 days spaceflight on glycogen synthase kinase 3 (GSK3) content and inhibitory serine phosphorylation in murine muscle bone samples from four separate missions (BION-M1, rodent research [RR]1, RR9, RR18). Spaceflight reduced GSK3β across all missions, whereas its was elevated with RR18 BION-M1. The reduction linked to type IIA fibers commonly observed as these are particularly enriched GSK3. then tested inhibiting GSK3 before this fiber shift, we demonstrate that muscle-specific Gsk3 knockdown increased mass, preserved strength, promoted oxidative Earth-based hindlimb unloading. In bone, activation enhanced after spaceflight; strikingly, deletion mineral density response Thus, future studies should test inhibition during spaceflight.