Skip to main content

Research Repository

Advanced Search

Spaceflight Induces Strength Decline in Caenorhabditis elegans

Soni, Purushottam; Edwards, Hunter; Anupom, Taslim; Rahman, Mizanur; Lesanpezeshki, Leila; Blawzdziewicz, Jerzy; Cope, Henry; Gharahdaghi, Nima; Scott, Daniel; Toh, Li Shean; Williams, Philip M.; Etheridge, Timothy; Szewczyk, Nathaniel; Willis, Craig R. G.; Vanapalli, Siva A.

Spaceflight Induces Strength Decline in Caenorhabditis elegans Thumbnail


Authors

Purushottam Soni

Hunter Edwards

Taslim Anupom

Mizanur Rahman

Leila Lesanpezeshki

Jerzy Blawzdziewicz

Henry Cope

Nima Gharahdaghi

DANIEL SCOTT DANIEL.SCOTT@NOTTINGHAM.AC.UK
Nottingham Research Fellow

PHIL WILLIAMS PHIL.WILLIAMS@NOTTINGHAM.AC.UK
Professor of Biophysics

Timothy Etheridge

Nathaniel Szewczyk

Craig R. G. Willis

Siva A. Vanapalli



Abstract

Background: Understanding and countering the well-established negative health consequences of spaceflight remains a primary challenge preventing safe deep space exploration. Targeted/personalized therapeutics are at the forefront of space medicine strategies, and cross-species molecular signatures now define the ‘typical’ spaceflight response. However, a lack of direct genotype–phenotype associations currently limits the robustness and, therefore, the therapeutic utility of putative mechanisms underpinning pathological changes in flight. Methods: We employed the worm Caenorhabditis elegans as a validated model of space biology, combined with ‘NemaFlex-S’ microfluidic devices for assessing animal strength production as one of the most reproducible physiological responses to spaceflight. Wild-type and dys-1 (BZ33) strains (a Duchenne muscular dystrophy (DMD) model for comparing predisposed muscle weak animals) were cultured on the International Space Station in chemically defined media before loading second-generation gravid adults into NemaFlex-S devices to assess individual animal strength. These same cultures were then frozen on orbit before returning to Earth for next-generation sequencing transcriptomic analysis. Results: Neuromuscular strength was lower in flight versus ground controls (16.6% decline, p < 0.05), with dys-1 significantly more (23% less strength, p < 0.01) affected than wild types. The transcriptional gene ontology signatures characterizing both strains of weaker animals in flight strongly corroborate previous results across species, enriched for upregulated stress response pathways and downregulated mitochondrial and cytoskeletal processes. Functional gene cluster analysis extended this to implicate decreased neuronal function, including abnormal calcium handling and acetylcholine signaling, in space-induced strength declines under the predicted control of UNC-89 and DAF-19 transcription factors. Finally, gene modules specifically altered in dys-1 animals in flight again cluster to neuronal/neuromuscular pathways, suggesting strength loss in DMD comprises a strong neuronal component that predisposes these animals to exacerbated strength loss in space. Conclusions: Highly reproducible gene signatures are strongly associated with space-induced neuromuscular strength loss across species and neuronal changes in calcium/acetylcholine signaling require further study. These results promote targeted medical efforts towards and provide an in vivo model for safely sending animals and people into deep space in the near future.

Citation

Soni, P., Edwards, H., Anupom, T., Rahman, M., Lesanpezeshki, L., Blawzdziewicz, J., …Vanapalli, S. A. (2023). Spaceflight Induces Strength Decline in Caenorhabditis elegans. Cells, 12(20), Article 2470. https://doi.org/10.3390/cells12202470

Journal Article Type Article
Acceptance Date Oct 15, 2023
Online Publication Date Oct 17, 2023
Publication Date 2023-10
Deposit Date Oct 19, 2023
Publicly Available Date Oct 19, 2023
Journal Cells
Electronic ISSN 2073-4409
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 12
Issue 20
Article Number 2470
DOI https://doi.org/10.3390/cells12202470
Keywords C. elegans; microgravity; muscle strength; muscle atrophy; spaceflight; dystrophin; International Space Station; omics; gene expression; astropharmacy
Public URL https://nottingham-repository.worktribe.com/output/26223963
Publisher URL https://www.mdpi.com/2073-4409/12/20/2470
Additional Information © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Files





You might also like



Downloadable Citations