Mammalian and Invertebrate Models as Complementary Tools for Gaining Mechanistic Insight on Muscle Responses to Spaceflight

Abstract

Bioinformatics approaches have proven useful in understanding biological responses to spaceflight. Spaceflight experiments remain resource intensive and rare. One outstanding issue is how to maximize scientific output from a limited number of omics datasets from traditional animal models including nematodes, fruitfly, and rodents. The utility of omics data from invertebrate models in anticipating mammalian responses to spaceflight has not been fully explored. Hence, we performed comparative analyses of transcriptomes of soleus and extensor digitorum longus (EDL) in mice that underwent 37 days of spaceflight. Results indicate shared stress responses and altered circadian rhythm. EDL showed more robust growth signals and Pde2a downregulation, possibly underlying its resistance to atrophy versus soleus. Spaceflight and hindlimb unloading mice shared differential regulation of proliferation, circadian, and neuronal signaling. Shared gene regulation in muscles of humans on bedrest and space flown rodents suggest targets for mitigating muscle atrophy in space and on Earth. Spaceflight responses of C. elegans were more similar to EDL. Discrete life stages of D. melanogaster have distinct utility in anticipating EDL and soleus responses. In summary, spaceflight leads to shared and discrete molecular responses between muscle types and invertebrate models may augment mechanistic knowledge gained from rodent spaceflight and ground-based studies.

Space omics research in Europe: Contributions, geographical distribution and ESA member state funding schemes

“…For example, the inactivation of genes related to neuronal or endocrine signaling extended life span on Earth ( Honda et al., 2012 ). More recently, European-based scientists described molecular responses to spaceflight across multiple organismal models including C. elegans , resulting in the identification of shared and discrete transcriptional responses across the animal kingdom ( Cahill et al., 2021 ). Microgravity and hypergravity transcriptomes have also been compared, highlighting transcriptional adaptations to altered gravitational load ( Willis et al., 2020 ).…”

“…Therefore, the purpose of this review is to provide a historical summary of Europe’s contribution to space omics from when records began through to summer 2020. Indeed, such research is continually being conducted, with numerous research articles more recently published in several special issues/collections (e.g ( Cahill et al., 2021 ; Madrigal et al., 2020 ). As such, our first aim was to identify and summarize peer-reviewed experimental publications performed in spaceflight or ground-based simulations, which include omics analysis and were (co)funded by ESA.…”

From Cultured Vascular Cells to Vessels: The Cellular and Molecular Basis of Vascular Dysfunction in Space

“…The analysis of eight RNA-seq datasets from NASA GeneLab on mice subjected to 37-day spaceflight mission demonstrates alteration of clock gene expressions in different tissues compared to ground control mice. Since glucocorticoids (GC) modulate the expression of clock genes via GC response elements, the increase of plasma and urine cortisol levels observed in spaceflown mice might contribute to the perturbation of the circadian rhythm ( Fujita et al, 2020 ; Cahill et al, 2021 ). It will be intriguing to broaden these studies to investigate the modulation of factors involved in vascular dysfunction in spaceflown rodents.…”

Detection of Target Genes for Drug Repurposing to Treat Skeletal Muscle Atrophy in Mice Flown in Spaceflight

“…Spaceflight experiments using mice are being conducted to determine the impact of microgravity on different muscle groups [ 1 ]. A major health problem in spaceflight is muscle wastage due to microgravity.…”