Tissue‐specific methylomic responses to a lifestyle intervention in older adults associate with metabolic and physiological health improvements
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.
Authors
- Fatih A. Bogaards (ORCID: https://orcid.org/0000-0003-2553-5346)
- Daniele Bizzarri (ORCID: https://orcid.org/0000-0002-6881-273X)
- Erik B. van den Akker (ORCID: https://orcid.org/0000-0002-7693-0728)
- Alexis Boulinguiez (ORCID: https://orcid.org/0000-0001-6886-6140)
- Ioannis Moustakas (ORCID: https://orcid.org/0000-0002-0293-8540)
- H. Eka D. Suchiman (ORCID: https://orcid.org/0000-0002-7168-5516)
- Lucy Sinke (ORCID: https://orcid.org/0000-0002-9209-1266)
- Gillian Butler‐Browne (ORCID: https://orcid.org/0000-0002-3431-242X)
- Thies Gehrmann (ORCID: https://orcid.org/0000-0003-4666-5406)
- C.P.G.M. de Groot (ORCID: https://orcid.org/0000-0003-2778-2789)
- Marian Beekman (ORCID: https://orcid.org/0000-0003-0585-6206)
- Capucine Trollet (ORCID: https://orcid.org/0000-0002-4838-3712)
- P. Eline Slagboom (ORCID: https://orcid.org/0000-0002-2875-4723)
- Bastiaan T. Heijmans (ORCID: https://orcid.org/0000-0001-5918-0534)
- Yotam Raz (ORCID: https://orcid.org/0000-0001-9628-632X)
- Melanie Waldenberger
- Nico Lakenberg
Institutions
- University of Antwerp (BE)
- Inserm (FR)
- Leiden University Medical Center (NL)
- Netherlands Bioinformatics Centre (NL)
- Helmholtz Zentrum München (DE)
- Sorbonne Université (FR)
- Astrophysique, Instrumentation et Modélisation (FR)
- German Centre for Cardiovascular Research (DE)
- Centre de Recherche en Myologie
- Wageningen University & Research (NL)
Publication Details
- Journal
- Aging Cell
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1111/acel.14431
- Citations
- 3
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 0.70
Funders
- ZonMw
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek