Tissue-specific methylomic responses to a lifestyle intervention in older adults associate with metabolic and physiological health improvements.

Autor: Sinke L; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands., Beekman M; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands., Raz Y; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands., Gehrmann T; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands.; Department of Bioscience Engineering, Research Group Environmental Ecology and Applied Microbiology, University of Antwerp, Antwerp, Belgium., Moustakas I; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands.; Sequencing Analysis Support Core, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands., Boulinguiez A; Myology Center for Research, U974, Sorbonne Université, INSERM, AIM, GH Pitié Salpêtrière Bat Babinski, Paris, France., Lakenberg N; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands., Suchiman E; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands., Bogaards FA; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands.; Division of Human Nutrition, Wageningen University and Research, Wageningen, The Netherlands., Bizzarri D; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands.; Delft Bioinformatics Lab, Pattern Recognition and Bioinformatics, Delft, The Netherlands., van den Akker EB; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands.; Delft Bioinformatics Lab, Pattern Recognition and Bioinformatics, Delft, The Netherlands., Waldenberger M; Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.; German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany., Butler-Browne G; Myology Center for Research, U974, Sorbonne Université, INSERM, AIM, GH Pitié Salpêtrière Bat Babinski, Paris, France., Trollet C; Myology Center for Research, U974, Sorbonne Université, INSERM, AIM, GH Pitié Salpêtrière Bat Babinski, Paris, France., de Groot CPGM; Division of Human Nutrition, Wageningen University and Research, Wageningen, The Netherlands., Heijmans BT; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands., Slagboom PE; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2024 Dec 01, pp. e14431. Date of Electronic Publication: 2024 Dec 01.
DOI: 10.1111/acel.14431
Abstrakt: Across the lifespan, diet and physical activity profiles substantially influence immunometabolic health. DNA methylation, as a tissue-specific marker sensitive to behavioral change, may mediate these effects through modulation of transcription factor binding and subsequent gene expression. Despite this, few human studies have profiled DNA methylation and gene expression simultaneously in multiple tissues or examined how molecular levels react and interact in response to lifestyle changes. The Growing Old Together (GOTO) study is a 13-week lifestyle intervention in older adults, which imparted health benefits to participants. Here, we characterize the DNA methylation response to this intervention at over 750 thousand CpGs in muscle, adipose, and blood. Differentially methylated sites are enriched for active chromatin states, located close to relevant transcription factor binding sites, and associated with changing expression of insulin sensitivity genes and health parameters. In addition, measures of biological age are consistently reduced, with decreases in grimAge associated with observed health improvements. Taken together, our results identify responsive molecular markers and demonstrate their potential to measure progression and finetune treatment of age-related risks and diseases.
(© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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