Abstract
Muscle atrophy is observed across species during spaceflight, however the sequence of molecular events that cause this phenomenon are not known. We flew liquid‐cultured C. elegans to the International Space Station, and assessed populations for movement rate before freezing on‐orbit at 4 and 8 d of flight. Post‐flight samples were analysed for genomic, proteomic, fat accumulation and targeted molecular changes versus 1G‐centrifuged flight samples. After 4 d spaceflight (first generation), animals displayed reduced movement rates versus 1G controls (1.53±0.64 vs. 2.61±0.12 Hz, respectively; P<0.01) and lowered whole‐body fat accumulation. Gene/protein expression profiles at 4 d flight showed reductions in several components involved in: a) the muscle contractile apparatus; b) cytoskeletal adhesion, and; c) mitochondrial function. This was accompanied by upregulation of daf‐16/foxo‐1 and sirt‐2.1/sirt‐1 and concurrent downregulation of sirtuin effectors abu‐6, abu‐7 and pqn‐5 (transmembrane components). However, second generation animals (8 d flight) displayed a return to 1G expression levels for all indices altered in the first generation. The exception was mitochondrial DNA content and associated gene expression, which remained depressed after 8 d flight. These results suggest that spaceflight‐sensitive mechanisms (insulin‐ and attachment‐mediated signalling) regulate an early metabolic downregulation, which recover in subsequent generations with lowered mitochondrial function remaining as a chronic adaptive response to microgravity. Such sustained mitochondrial impairment could reduce cellular energy sufficiently to account for chronic declines in muscle mass and function.
Published Version
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