Systems biologist decoding how epigenetics shapes ageing and age-related disease.
I’m am a King’s Prize Fellow establishing my own research programme at the Department for Twin Research at King’s College London, with additional affiliations at the European Translational Oncology Prevention and Screening Institute (EUTOPS; Universität Innsbruck) and the Institute for Women’s Health (University College London; honorary research fellow).
My research sits at the interface of computational and experimental biology and clinical research, focusing how epigenetic regulation - particularly DNA methylation - shapes ageing and age-related disease. I’m passionate about uncovering the molecular basis of ageing, developing robust biomarkers to monitor individual biological ageing, and exploring how targeted interventions can modulate these processes. Together with Prof. Martin Widschwendter (UIBK, UCL, Karolinska), I co-led the TirolGESUND study (ClinicalTrials.gov NCT05678426, a longitudinal, multi-omic study profiling the effects of intermittent fasting and smoking cessation across multiple tissues, and I continue to intgrate human multi-omic datasets with experimental approaches to dissect causal mechanisms underlying ageing.
As member of the Biomarkers of Aging Consortium Executive Committee, I actively promote standardisation for research into biomarkers of aging, and I have a special interest in employing more robust methods to advance molecular biomarkers into promising clinical tools for personalized disease prevention.
Ultimately, my work is driven by the vision to move beyond risk prediction to mechanistic understanding - identifying which ageing processes drive disease and how we can intervene to maintain health across lifespan.
Extending human healthspan requires understanding how lifestyle interventions impact molecular systems across tissues and time. Here, we present the TirolGESUND Lifestyle Atlas (ClinicalTrials.gov: NCT05678426), a longitudinal, multi-modal resource profiling 156 healthy women (aged 30-60 years) undergoing 6-month intermittent fasting (n=114) or smoking cessation (n=42) interventions. Participants were sampled up to four times across seven tissues and fluids, generating >3,450 biospecimens with harmonised DNA methylation, metabolomics, microbiome, and immune profiling, alongside skin histology, barrier measurements, and rich clinical metadata. We demonstrate the utility of this dataset through: (i) multi-omics-wide association studies linking traits to molecular features; (ii) integrative factor modelling revealing coordinated cross-tissue signatures; (iii) epigenetic-biomarker cross-omic associations, and (iv) CpG-level variance decomposition mapping stable, individual-specific, tissue-restricted, and intervention-responsive methylation patterns. We further show that ageing-linked features are selectively malleable: highly compliant intermittent fasting participants exhibited attenuated or even age-opposing molecular trajectories within six months. The atlas enables unprecedented within-cohort comparisons across omic layers and tissues, supporting discovery of context-dependent biomarkers, cross-system coordination, and intervention responsiveness. Data are available via an interactive portal, with sensitive data under controlled access (https://eutops.github.io/lifestyle-atlas/). This resource provides a foundation for exploring biomarker association and multi-tissue epigenetics, enabling hypothesis generation and benchmarking for systems biology and human healthspan research. Multi-tissue multi-modal profiling of two clinically-relevant lifestyle interventions in 156 women aged 30-60 Intermittent fasting modifies ageing-linked molecular features in an age-opposing direction Cross-tissue epigenetic biomarker mapping links immunity, metabolism, and microbiome Tissue-specific epigenetic plasticity maps reveal candidate meQTLs, Data sharing and interactive portal enable broad reuse for hypothesis generation and exploration
Systems epigenetic approach towards non-invasive breast cancer detection
Chiara Herzog, Bente Theeuwes, Allison Jones, and 8 more authors
No study has systematically compared the suitability of DNA methylation (DNAme) profiles in non-invasive samples for the detection of breast cancer (BC). We assess non-tumour DNAme in 1,100 cervical, buccal, and blood samples from BC cases and controls and find that cervical samples exhibit the largest nuber of differentially methylated sites, followed by buccal samples. No sites were significant in blood after FDR adjustment. Deriving DNAme-based classifiers for BC detection in each sample type (WID-buccal-, cervical-, or blood-BC), we achieve validation AUCs of 0.75, 0.66, and 0.51, respectively. Buccal and cervical BC-associated DNAme alterations distinguish between BC cases and controls in both surrogate and breast tissue (AUC > 0.88), yet individual sites and the directionality of methylation changes are not identical between these two sample types, and buccal sample DNAme aligns with breast methylation changes more closely. Pending additional validation, these insights may have the potential to improve non-invasive personalized BC prevention.
2024
Challenges and recommendations for the translation of biomarkers of aging
Chiara Herzog*, Ludger J E Goeminne*, Jesse R Poganik*, and 31 more authors
Biomarkers of aging (BOA) are quantitative parameters that predict biological age and ideally its changes in response to interventions. In recent years, many promising molecular and omic BOA have emerged with an enormous potential for translational geroscience and improving healthspan. However, clinical translation remains limited, in part due to the gap between preclinical research and the application of BOA in clinical research and other translational settings. We surveyed experts in these areas to better understand current challenges for the translation of aging biomarkers. We identified six key barriers to clinical translation and developed guidance for the field to overcome them. Core recommendations include linking BOA to clinically actionable insights, improving affordability and availability to broad populations and validation of biomarkers that are robust and responsive at the level of individuals. Our work provides key insights and practical recommendations to overcome barriers impeding clinical translation of BOA. Biomarkers of aging have potential to accelerate the clinical translation of interventions that promote healthy aging but are currently limited to research. The authors identify six barriers to be overcome to enable biomarker translation, providing a roadmap to clinical implementation.
Cigarette smoking and e-cigarette use induce shared DNA methylation changes linked to carcinogenesis
Chiara Herzog, Allison Jones, Iona Evans, and 7 more authors
Tobacco use is a major modifiable risk factor for adverse health outcomes, including cancer, and elicits profound epigenetic changes thought to be associated with long-term cancer risk. While electronic cigarettes (e-cigarettes) have been advocated as harm reduction alternatives to tobacco products, recent studies have revealed potential detrimental effects, highlighting the urgent need for further research into the molecular and health impacts of e-cigarettes. Here, we applied computational deconvolution methods to dissect the cell- and tissue-specific epigenetic effects of tobacco or e-cigarette use on DNA methylation (DNAme) in over 3,500 buccal/saliva, cervical, or blood samples, spanning epithelial and immune cells at directly and indirectly exposed sites. The 535 identified smoking-related DNAme loci (CpGs) clustered into four functional groups, including detoxification or growth signaling, based on cell type and anatomical site. Loci hypermethylated in buccal epithelial cells of smokers associated with NOTCH1/RUNX3/growth factor receptor signaling also exhibited elevated methylation in cancer tissue and progressing lung carcinoma in situ lesions, and hypermethylation of these sites predicted lung cancer development in buccal samples collected from smokers up to 22 years prior to diagnosis, suggesting a potential role in driving carcinogenesis. Alarmingly, these CpGs were also hypermethylated in e-cigarette users with a limited smoking history. This study sheds light on the cell type-specific changes to the epigenetic landscape induced by smoking-related products.
2023
Biomarkers of aging for the identification and evaluation of longevity interventions
Mahdi Moqri*, Chiara Herzog*, Jesse R. Poganik*, and 25 more authors
With the rapid expansion of aging biology research, the identification and evaluation of longevity interventions in humans have become key goals of this field. Biomarkers of aging are critically important tools in achieving these objectives over realistic time frames. However, the current lack of standards and consensus on the properties of a reliable aging biomarker hinders their further development and validation for clinical applications. Here, we advance a framework for the terminology and characterization of biomarkers of aging, including classification and potential clinical use cases. We discuss validation steps and highlight ongoing challenges as potential areas in need of future research. This framework sets the stage for the development of valid biomarkers of aging and their ultimate utilization in clinical trials and practice.
2022
A Simple Cervicovaginal Epigenetic Test for Screening and Rapid Triage of Women With Suspected Endometrial Cancer: Validation in Several Cohort and Case/Control Sets
Chiara Herzog*, Fátima Marín*, Allison Jones, and 28 more authors
PURPOSE: Endometrial cancer (EC) incidence has been rising over the past 10 years. Delays in diagnosis reduce survival and necessitate more aggressive treatment. We aimed to develop and validate a simple, noninvasive, and reliable triage test for EC to reduce the number of invasive diagnostic procedures and improve patient survival. METHODS: We developed a test to screen and triage women with suspected EC using 726 cervical smear samples from women with and without EC, and validated the test in 562 cervicovaginal samples using three different collection methods (cervical smear: n = 248; vaginal swab: n = 63; and self-collection: n = 251) and four different settings (case/control: n = 388; cohort of women presenting with postmenopausal bleeding: n = 63; a cohort of high-risk women with Lynch syndrome: n = 25; and a nested case/control setting from a screening cohort and samples taken up to 3 years before EC diagnosis: n = 86). RESULTS: We describe the Women’s cancer risk IDentification – quantitative polymerase chain reaction test for Endometrial Cancer (WID-qEC), a three-marker test that evaluates DNA methylation in gene regions of GYPC and ZSCAN12. In cervical, self-collected, and vaginal swab samples derived from symptomatic patients, it detected EC with sensitivities of 97.2% (95% CI, 90.2 to 99.7), 90.1% (83.6 to 94.6), and 100% (63.1 to 100), respectively, and specificities of 75.8% (63.6 to 85.5), 86.7% (79.3 to 92.2), and 89.1% (77.8 to 95.9), respectively. The WID-qEC identified 90.9% (95% CI, 70.8 to 98.9) of EC cases in samples predating diagnosis up to 1 year. Test performance was similar across menopausal status, age, stage, grade, ethnicity, and histology. CONCLUSION: The WID-qEC is a noninvasive reliable test for triage of women with symptoms suggestive of ECs. Because of the potential for self-collection, it could improve early diagnosis and reduce the reliance for in-person visits.
