Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun;34(6):7958-7969.
doi: 10.1096/fj.201902976R. Epub 2020 Apr 15.

Three months of bed rest induce a residual transcriptomic signature resilient to resistance exercise countermeasures

Rodrigo Fernandez-Gonzalo  1 , Per A Tesch  2 , Tommy R Lundberg  1 , Björn A Alkner  3   4 , Eric Rullman  1 , Thomas Gustafsson  1
Affiliations
Free article

Three months of bed rest induce a residual transcriptomic signature resilient to resistance exercise countermeasures

Rodrigo Fernandez-Gonzalo et al. FASEB J. 2020 Jun.
Free article

Abstract

This study explored the muscle genome-wide response to long-term unloading (84-day bed rest) in 21 men. We hypothesized that a part of the bed rest-induced gene expression signature would be resilient to a concurrent flywheel resistance exercise (RE) countermeasure. Using DNA microarray technology analyzing 35 345 gene-level probe-sets, we identified 335 annotated probe-sets that were downregulated, and 315 that were upregulated after bed rest (P < .01). Besides a predictable differential expression of genes and pathways related to mitochondria (downregulation; false-discovery rates (FDR) <1E-04), ubiquitin system (upregulation; FDR = 3E-02), and skeletal muscle energy metabolism and structure (downregulation; FDR ≤ 3E-03), 84-day bed rest also altered circadian rhythm regulation (upregulation; FDR = 3E-02). While most of the bed rest-induced changes were counteracted by RE, 209 transcripts were resilient to the exercise countermeasure. Genes upregulated after bed rest were particularly resistant to training (P < .001 vs downregulated, non-reversed genes). Specifically, "Translation Factors," "Proteasome Degradation," "Cell Cycle," and "Nucleotide Metabolism" pathways were not normalized by RE. This study provides an unbiased high-throughput transcriptomic signature of one of the longest unloading periods in humans to date. Classical disuse-related changes in structural and metabolic genes/pathways were identified, together with a novel upregulation of circadian rhythm transcripts. In the context of previous bed rest campaigns, the latter seemed to be related to the duration of unloading, suggesting the transcriptomic machinery continues to adapt throughout extended disuse periods. Despite that the RE training offset most of the bed rest-induced muscle-phenotypic and transcriptomic alterations, we contend that the human skeletal muscle also displays a residual transcriptomic signature of unloading that is resistant to an established exercise countermeasure.

Keywords: atrophy; microarray; muscle wasting; unloading.

PubMed Disclaimer

References

REFERENCES

    1. Alkner BA, Tesch PA. Knee extensor and plantar flexor muscle size and function following 90 days of bed rest with or without resistance exercise. Eur J Appl Physiol. 2004;93:294-305.
    1. Berg HE, Larsson L, Tesch PA. Lower limb skeletal muscle function after 6 wk of bed rest. J Appl Physiol. 1997;82:182-188.
    1. Haus JM, Carrithers JA, Carroll CC, Tesch PA, Trappe TA. Contractile and connective tissue protein content of human skeletal muscle: effects of 35 and 90 days of simulated microgravity and exercise countermeasures. Am J Physiol Regul Integr Comp Physiol. 2007;293:R1722-R1727.
    1. Trappe S. Effects of spaceflight, simulated spaceflight and countermeasures on single muscle fiber physiology. J Gravit Physiol. 2002;9:P323-P326.
    1. Trappe S, Creer A, Slivka D, Minchev K, Trappe T. Single muscle fiber function with concurrent exercise or nutrition countermeasures during 60 days of bed rest in women. J Appl Physiol. 2007;103:1242-1250.

Publication types