Next-generation biomarkers of aging: multi-omics clocks, robustness, and mechanism

The field of aging research is rapidly evolving, driven by the quest to accurately and reliably quantify biological aging across diverse populations. Traditional chronological measures often miss the nuanced trajectories and vast individual variability in aging, fueling the emergence of molecular biomarkers- particularly multi-omics “aging clocks.” Recent progress in omics technologies has led to the proliferation of clocks based on epigenomic, transcriptomic, proteomic, and metabolomic signatures, offering unprecedented resolution for estimating biological age. However, several unresolved questions remain, including how robust these clocks are across populations, how distinct molecular layers interact, and the extent to which these measures reflect underlying aging mechanisms rather than mere statistical associations. Furthermore, ongoing debates persist around the interpretability, fairness, and ultimate clinical utility of such biomarkers.This Research Topic aims to catalyze advances in next-generation biomarkers of aging by fostering interdisciplinary dialogue and methodological innovation. Key objectives include enhancing the robustness and generalizability of multi-omics aging clocks, elucidating their connection to core biological processes of aging, and clarifying how these biomarkers respond to interventions that target healthspan or age-related disease. We seek to answer critical questions such as: How do integrated omics clocks perform across different demographic groups and environmental contexts? What are the computational and statistical strategies best suited for building interpretable yet robust clocks? To what extent do these metrics reflect biological mechanisms of aging and provide mechanistic insights beyond statistical prediction, and how can they inform the design or assessment of anti-aging interventions?This Research Topic encompasses research that develops, compares, or challenges multi-omics clocks of aging, with a focus on expanding explanatory power and utility. The scope includes, but is not limited to, studies that address the following themes:o Methodological advances in multi-omics clock construction and validationo Assessment of clock robustness, reproducibility, cross-platform comparability, and generalizability across independent cohorts o Integrative analyses linking multi-layered omics datao Circulating biomarkers of aging, including plasma proteomics and metabolomics signatures, and their translational potentialo Mechanistic studies connecting clock measures with aging processes (e.g., senescence, inflammation, mitochondrial function)o Evaluation of biomarker sensitivity to lifestyle, pharmacological, or regenerative interventionso Harmonization of multi-omics clocks with clinical, functional, or imaging assessments of agingo Translation of aging biomarkers into clinical research, including risk prediction, disease stratification, therapeutic monitoring, and intervention studies.o Application of artificial intelligence and machine learning for interpretable, scalable aging biomarker discoveryThis Topic especially encourages original research, reviews, methods, and theoretical perspectives that push the boundaries of current understanding and set the stage for actionable, interpretable aging biomarkers. Topic editors: Yumin Ma, Sara Ahadi, Ming-Feng Hsueh Source: https://www.frontiersin.org/research-topics/83638/next-generation-biomarkers-of-aging-multi-omics-clocks-robustness-and-mechanism