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From ageing clocks to organ networks: Biological age-driven organ asynchrony and inter-organ interactions shaping
Zhenyu Li1, Jiahao Liu1, Yaoyao Dai1
1Department of Epidemiology, Institute for Applied Research in Public Health, Key Laboratory of Jiangsu Higher Education Institutions for Advanced Medical Analytics and Public Health, School of Public Health, Nantong University, Nantong, Jiangsu, China.
Abstract:
Ageing is a multidimensional and heterogeneous process that progresses asynchronously across organ systems. Advances in multi-omics technologies have led to the development of diverse ageing clocks, including epigenetic, proteomic, metabolomic, and imaging-based models, which extend beyond estimating crude biological age to more precisely capture organ-specific ageing trajectories and predict age-related diseases and mortality risk. Population-scale studies demonstrate substantial within-individual variation in organ-ageing rates, showing that accelerated ageing in specific organs and increased numbers of aged organs markedly contribute to systemic dysregulation and elevated mortality risk. Multi-organ-ageing clocks further highlight the role of organ crosstalk networks, such as cardiovascular-pulmonary-cerebral interactions, in shaping healthspan and survival. Building on these insights, we propose a conceptual artificial intelligence (AI)-driven multi-omics health platform that integrates clinical data, imaging, wearable sensors, and organ-specific ageing clocks to enable continuous monitoring of biological age and early risk detection. This platform supports stratified management, whereby individuals with mild ageing may benefit from lifestyle-based interventions, while those with accelerated or multi-organ ageing receive personalised pharmacological and clinical strategies. Together, multi-omics ageing clocks and AI-enabled analytics provide a transformative framework for understanding human ageing, shifting from single-organ assessment to network-level evaluation and precision anti-ageing interventions. These advances lay the groundwork for a scalable national health ecosystem aimed at extending healthy lifespan and reducing population-wide mortality risk.
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