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Sinke, L.* ; Beekman, M.* ; Raz, Y.* ; Gehrmann, T.* ; Moustakas, I.* ; Boulinguiez, A.* ; Lakenberg, N.* ; Suchiman, E.* ; Bogaards, F.A.* ; Bizzarri, D.* ; van den Akker, E.B.* ; Waldenberger, M. ; Butler-Browne, G.* ; Trollet, C.* ; de Groot, C.P.G.M.* ; Heijmans, B.T.* ; Slagboom, P.E.*

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

Aging Cell:e14431 (2024)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Dna Methylation ; Epigenomics ; Functional Genomics ; Healthy Aging ; Lifestyle ; Metabolism ; Muscle; Human Skeletal-muscle; Dna Methylation; Transcription Factors; Exercise; Grb10; Gene; Expression; Strategies; Design; Impact

ISSN (print) / ISBN 1474-9718

e-ISSN 1474-9726

Journal Aging Cell

Quellenangaben Article Number: e14431

Publisher Wiley

Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)

Grants Nederlandse Organisatie voor Wetenschappelijk onderzoek