Secondary integrated analysis of multi-tissue transcriptomic responses to a combined lifestyle intervention in older adults from the GOTO nonrandomized trial
Nature Communications, vol. 15, pp. 7013
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. Molecular effects of lifestyle interventions are typically studied within one tissue, neglecting potential shared responses across tissues. Here, the authors show that subcutaneous adipose tissue RNA levels best capture health benefits of the intervention and identified joint effects among blood, subcutaneous adipose tissue and muscle tissue RNA levels.
Authors 8
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Leiden University Medical Center · Wageningen University & Research
Affiliation as printed
Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands. f.a.bogaards@lumc.nl
Leiden Computational Biology Center, Leiden, The Netherlands. f.a.bogaards@lumc.nl
Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. f.a.bogaards@lumc.nl
Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University · University of Antwerp · Leiden University Medical Center
Affiliation as printed
Department of Bioscience Engineering, Lab of Applied Microbiology and Biotechnology, University of Antwerp, Antwerp, Belgium
Leiden Computational Biology Center, Leiden, The Netherlands
Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
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Wageningen University & Research
Affiliation as printed
Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands
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Leiden University · Delft University of Technology
Affiliation as printed
Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands
Leiden Computational Biology Center, Leiden, The Netherlands
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Leiden University Medical Center · Max Planck Institute for Biology of Ageing · Delft University of Technology
Affiliation as printed
Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands
Max Planck Institute for Biology of Aging, Cologne, Germany
Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
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