A novel framework to build saliva-based DNA methylation biomarkers: Quantifying systemic chronic inflammation as a case study
Abstract
Accessible and non-invasive biomarkers that measure human ageing processes and the risk of developing age-related disease are paramount in preventative healthcare. Here, we describe a novel framework to train saliva-based DNA methylation (DNAm) biomarkers that are reproducible and biologically interpretable. By leveraging a reliability dataset with replicates across tissues, we demonstrate that it is possible to transfer knowledge from blood DNAm to saliva DNAm data using DNAm proxies of blood proteins (EpiScores). We apply these methods to create a new saliva-based epigenetic clock (InflammAge) that quantifies systemic chronic inflammation (SCI) in humans. Using a large blood DNAm human cohort with linked electronic health records and over 18,000 individuals (Generation Scotland), we demonstrate that InflammAge significantly associates with all-cause mortality, disease outcomes, lifestyle factors, and immunosenescence; in many cases outperforming the widely used SCI biomarker C-reactive protein (CRP). We propose that our biomarker discovery framework and InflammAge will be useful to improve understanding of the molecular mechanisms underpinning human ageing and to assess the impact of gero-protective interventions.
Author
Schmunk, Lisa J
Call, Toby P
McCartney, Daniel L
Javaid, Hira
Hastings, Waylon J
Jovicevic, Vanja
Kojadinović, Dragoljub
Tomkinson, Natacha
Zlamalova, Eliska
McGee, Kirsty C
Sullivan, Jack
Campbell, Archie
McIntosh, Andrew M
Óvári, Veronika
Wishart, Karl
Behrens, Christian E
Stone, Emma
Gavrilov, Miloš
Thompson, Rob
Jackson, Thomas
Lord, Janet M
Stubbs, Thomas M
Marioni, Riccardo E
Martin-Herranz, Daniel E
Call, Toby P
McCartney, Daniel L
Javaid, Hira
Hastings, Waylon J
Jovicevic, Vanja
Kojadinović, Dragoljub
Tomkinson, Natacha
Zlamalova, Eliska
McGee, Kirsty C
Sullivan, Jack
Campbell, Archie
McIntosh, Andrew M
Óvári, Veronika
Wishart, Karl
Behrens, Christian E
Stone, Emma
Gavrilov, Miloš
Thompson, Rob
Jackson, Thomas
Lord, Janet M
Stubbs, Thomas M
Marioni, Riccardo E
Martin-Herranz, Daniel E
Date
2025-01-30
Type
Article
Subject
Oncology. Pathology.::Genetics
Collections
Citation
Schmunk LJ, Call TP, McCartney DL, Javaid H, Hastings WJ, Jovicevic V, Kojadinović D, Tomkinson N, Zlamalova E, McGee KC, Sullivan J, Campbell A, McIntosh AM, Óvári V, Wishart K, Behrens CE, Stone E, Gavrilov M, Thompson R; Hurdle bio‐infrastructure team; Jackson T, Lord JM, Stubbs TM, Marioni RE, Martin-Herranz DE. A novel framework to build saliva-based DNA methylation biomarkers: Quantifying systemic chronic inflammation as a case study. Aging Cell. 2025 Apr;24(4):e14444. doi: 10.1111/acel.14444. Epub 2025 Jan 30.
Journal / Source Title
Aging Cell
DOI
10.1111/acel.14444
PMID
39888134
Publisher
Willey-Blackwell
Publisher’s URL
https://onlinelibrary.wiley.com/journal/14749726