A Multimodal Framework for Organ- and Cell-Resolved Biological Aging and Longevity Intervention Discovery

May 25, 2026medRxiv : the preprint server for health sciences

A combined approach to study aging in organs and cells and find treatments to extend lifespan

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Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

mAge predicts biological age with a test Rand of 0.87 and a mean error of 2.3 years.

Integration of plasma proteomics and wearable data improves age and mortality predictions compared to traditional methods.
mAge reduces mortality prediction error by 21% compared to unimodal baseline approaches.
Organ- and cell type-specific biological clocks highlight the most significant aging signatures in cardiac, immune, and intracellular proteins.
Identified interventions such as GLP-1 receptor agonists and gabapentin are associated with lower proteomic age and mortality risk.
Mapping to FDA-approved drug targets supports the potential for personalized longevity interventions based on continuous monitoring.

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Aging is the primary driver of chronic disease and mortality, requiring comprehensive frameworks for quantification of aging and nomination of longevity interventions. We developed mAge (multimodal age), a biological aging framework that integrates plasma proteomics, wearables, and mortality hazard to predict biological age, intrinsic capacity, and mortality risk. By combining proteomic and wearable data in UK Biobank samples, mAge exceeds unimodal baseline age prediction to 0.87 test Rand 2.3 years mean error, and reduces unimodal baseline mortality prediction error by 21%. We further constructed organ- and cell type-specific biological clocks that quantify aging across 49 distinct subsystems, revealing that cardiac, immune, and intracellular protein signatures benefit most from wearable integration. By mapping data to FDA-approved drug targets, we identified interventions, such as GLP-1 receptor agonists, gabapentin, and ACE inhibitors, that are associated with lower overall and subsystem-specific proteomic age and mortality risk or are associated with longer time-to-death and later age-at-death in longitudinal and deceased cohorts. mAge establishes a scalable framework for nominating and validating personalized longevity interventions, bridging continuous digital monitoring with molecular aging diagnostics. 2