Integrative Biomedical Research

Integrative Biomedical Research (Journal of Angiotherapy) | Online ISSN  3068-6326
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Integrative Biomedical Research 10 (1) 1-8 https://doi.org/10.25163/biomedical.10110885

Submitted: 19 February 2026 Revised: 07 April 2026  Accepted: 16 April 2026  Published: 18 April 2026 


Abstract

Chronological age is a poor proxy for the true physiological state of an individual, and this mismatch has driven a decade-long search for molecular biomarkers capable of tracking biological age directly. Among the candidates that have emerged from genomics, transcriptomics, proteomics and metabolomics, biomarkers derived from DNA methylation—so-called epigenetic clocks—have proved the most reproducible and the most clinically informative. Here we trace their evolution from first-generation estimators trained to predict chronological age, through second-generation clocks trained on clinical morbidity and mortality outcomes, to third-generation “pace of ageing” metrics and, most recently, resilience-oriented multi-omics frameworks such as EpiAge-R that attempt to separate degenerative methylation noise from active repair signal. We show how epigenetic age acceleration tracks mortality, cardiovascular disease, cancer, neurodegeneration and frailty across large cohorts, how minimalist targeted-CpG assays are beginning to make biological age screening scalable outside specialist laboratories, and how randomized and pilot trials of multidomain lifestyle, dietary and micronutrient interventions have repeatedly demonstrated measurable deceleration—and in some cohorts apparent reversal—of biological age. We argue that epigenetic clocks are best understood not as static descriptive biomarkers but as dynamic, intervention-sensitive endpoints, and we outline the technical noise, tissue specificity and population-reference biases that currently stand between this promise and its responsible use in individual patients.

Keywords: epigenetic clocks; DNA methylation; biological age; geroscience; epigenetic age acceleration; longevity intervention; EpiAge-R

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