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
Hurdle.Bio/Chronomics Ltd., London, UK.
Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Aging Cell. 2025 Apr;24(4):e14444. doi: 10.1111/acel.14444. Epub 2025 Jan 30.
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.
在预防性医疗保健中，能够测量人类衰老过程以及患与年龄相关疾病风险的可获取且非侵入性的生物标志物至关重要。在此，我们描述了一个新的框架，用于训练基于唾液的可重复且具有生物学可解释性的DNA甲基化（DNAm）生物标志物。通过利用一个跨组织有重复样本的可靠性数据集，我们证明可以使用血液蛋白质的DNAm代理（EpiScores）将血液DNAm的知识转移到唾液DNAm数据中。我们应用这些方法创建了一个新的基于唾液的表观遗传时钟（InflammAge），用于量化人类的全身慢性炎症（SCI）。利用一个拥有关联电子健康记录的大型血液DNAm人类队列以及超过18000名个体（苏格兰世代研究），我们证明InflammAge与全因死亡率、疾病结局、生活方式因素和免疫衰老显著相关；在许多情况下，其表现优于广泛使用的SCI生物标志物C反应蛋白（CRP）。我们提出，我们的生物标志物发现框架和InflammAge将有助于增进对人类衰老基础分子机制的理解，并评估老年保护干预措施的影响。
