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Secondary integrated analysis of multi-tissue transcriptomic responses to a combined lifestyle intervention in older adults from the GOTO nonrandomized trial

Author

Listed:
  • F. A. Bogaards

    (Leiden University Medical Center
    Leiden Computational Biology Center
    Wageningen University & Research)

  • T. Gehrmann

    (Leiden University Medical Center
    Leiden Computational Biology Center
    University of Antwerp)

  • M. Beekman

    (Leiden University Medical Center)

  • N. Lakenberg

    (Leiden University Medical Center)

  • H. E. D. Suchiman

    (Leiden University Medical Center)

  • C. P. G. M. Groot

    (Wageningen University & Research)

  • M. J. T. Reinders

    (Leiden Computational Biology Center
    Delft University of Technology)

  • P. E. Slagboom

    (Leiden University Medical Center
    Delft University of Technology
    Max Planck Institute for Biology of Aging)

Abstract

Molecular effects of lifestyle interventions are typically studied in a single tissue. Here, we perform a secondary analysis on the sex-specific effects of the Growing Old TOgether trial (GOTO, trial registration number GOT NL3301 ( https://onderzoekmetmensen.nl/nl/trial/27183 ), NL-OMON27183 , primary outcomes have been previously reported in ref. 1), a moderate 13-week combined lifestyle intervention on the transcriptomes of postprandial blood, subcutaneous adipose tissue (SAT) and muscle tissue in healthy older adults, the overlap in effect between tissues and their relation to whole-body parameters of metabolic health. The GOTO intervention has virtually no effect on the postprandial blood transcriptome, while the SAT and muscle transcriptomes respond significantly. In SAT, pathways involved in HDL remodeling, O2/CO2 exchange and signaling are overrepresented, while in muscle, collagen and extracellular matrix pathways are significantly overexpressed. Additionally, we find that the effects of the SAT transcriptome closest associates with gains in metabolic health. Lastly, in males, we identify a shared variation between the transcriptomes of the three tissues. We conclude that the GOTO intervention has a significant effect on metabolic and muscle fibre pathways in the SAT and muscle transcriptome, respectively. Aligning the response in the three tissues revealed a blood transcriptome component which may act as an integrated health marker for metabolic intervention effects across tissues.

Suggested Citation

  • F. A. Bogaards & T. Gehrmann & M. Beekman & N. Lakenberg & H. E. D. Suchiman & C. P. G. M. Groot & M. J. T. Reinders & P. E. Slagboom, 2024. "Secondary integrated analysis of multi-tissue transcriptomic responses to a combined lifestyle intervention in older adults from the GOTO nonrandomized trial," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50693-3
    DOI: 10.1038/s41467-024-50693-3
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    References listed on IDEAS

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    1. Linda Partridge & Joris Deelen & P. Eline Slagboom, 2018. "Facing up to the global challenges of ageing," Nature, Nature, vol. 561(7721), pages 45-56, September.
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