Integrative transcriptomics identifies an 18-gene candidate blood-accessible biomarker panel for longitudinal monitoring of spaceflight-induced muscle atrophy.

Authors

Jae Ho Shim, Ji Yeon Lee, Jihye Han, Hyeon Soo Kim

Published in

PloS one. Volume 21. Issue 10. Pages e0358130. Epub Oct 07, 2026.

Abstract

Skeletal muscle atrophy is a critical physiological risk during long-duration spaceflight, yet candidate blood-accessible transcriptomic biomarkers for longitudinal monitoring remain unavailable. We developed an integrative multi-mission framework combining a primary discovery transcriptome from THP-1 monocytic cells exposed to International Space Station (ISS) microgravity (GEO: Sci. Adv. 2026 (https://doi.org/10.1126/sciadv.adw7832, Data S1-S10); NASA OSDR: Al-Ahmadi et al. 2026; n = 8 spaceflight, 8 ground control) - yielding 4,522 spaceflight-differentially expressed genes (SDEGs) - with a PRISMA-compliant meta-analysis of 46 verified spaceflight studies, producing a 726-gene consensus set. Cross-referencing these datasets identified 103 intersection genes; application of our Integrated Concordance Score (ICS) nominated an 18-gene candidate biomarker panel nominated across six external missions. Orthogonal cross-tissue concordance analysis using six C2C12 myotube simulated-microgravity datasets demonstrated Pearson r = 0.79 (95% CI 0.52-0.92, p < 0.001), with a conserved stress module achieving r = 0.88; complementary concordance in human primary skeletal myotubes confirmed tri-model directional concordance for 13 stress-module genes. Gold-tier biomarkers (TNNT3, TRIM63, ACTC1, IGF2; ICS ≥ 8.0) showed ≥83% multi-mission concordance. Temporal modelling informs a preliminary two-tier fortnightly/monthly monitoring framework aligned with measured saturation kinetics, and the prioritised panel converges on coordinated ubiquitin-proteasome activation, AKT-mTOR-FOXO3a remodelling, E2F suppression, and sarcomeric reprogramming. Integrated drug-gene analysis identified bimagrumab combined with leucine as the top predicted prioritised countermeasure pair (computational Bliss = 2.8). These findings establish a proposed candidate blood-accessible biomarker framework for periodic muscle health surveillance during long-duration human spaceflight, available prospective validation in astronaut blood samples. The unit of analysis was the analytical contrast (spaceflight vs. matched ground control), not the publication. Cross-platform harmonization was performed via gene-level mapping and rank-based normalization.

PMID:
42842563
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

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