Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Leiden Computational Biology Center, Leiden, The Netherlands.
Nat Commun. 2024 Aug 15;15(1):7013. doi: 10.1038/s41467-024-50693-3.
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. ), 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, O/CO 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.
生活方式干预的分子效应通常在单一组织中进行研究。在这里，我们对 Growing Old TOgether 试验（GOTO，试验注册号 GOT NL3301（https://onderzoekmetmensen.nl/nl/trial/27183），NL-OMON27183，主要结果先前已在参考文献中报道）的性别特异性效应进行了二次分析，该试验是一项适度的 13 周综合生活方式干预，针对健康老年人的餐后血液、皮下脂肪组织（SAT）和肌肉组织的转录组，组织之间的重叠效应及其与代谢健康的全身参数的关系。GOTO 干预对餐后血液转录组几乎没有影响，而 SAT 和肌肉转录组则有明显反应。在 SAT 中，涉及 HDL 重塑、O/CO 交换和信号转导的途径被过度表达，而在肌肉中，胶原和细胞外基质途径则显著过表达。此外，我们发现 SAT 转录组的影响与代谢健康的改善最密切相关。最后，在男性中，我们在三种组织的转录组之间发现了一个共同的变异。我们得出的结论是，GOTO 干预分别对 SAT 和肌肉转录组中的代谢和肌肉纤维途径有显著影响。三个组织的反应一致表明，血液转录组成分可能作为代谢干预效果在组织间的综合健康标志物。
