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Abila, E.* ; Buljan, I.* ; Zheng, Y.* ; Kleißl, L.* ; Klotz, S.* ; Veres, T.* ; Weng, Z.* ; Nackenhorst, M.* ; Kamies, R. ; Michl, A. ; Kadri, S. ; Moustafa, S.* ; Hulla, W.* ; Perkonigg, M.* ; Drach, M.* ; Tschandl, P.* ; Sterniczky, B.* ; Heinig, M. ; Desadeleer, L.* ; WUYTS, W.* ; Vanaudenaerde, B.* ; Ceulemans, L.* ; Buchanan, D.* ; Fennell, L.* ; Stary, G.* ; Tolkach, Y.* ; Wöhrer, A.* ; Schiller, H.B. ; Rendeiro, A.*

Histological aging signatures for monitoring tissue-specific aging and disease.

Nat. Med., DOI: 10.1038/s41591-026-04566-5 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Aging is the primary risk factor for chronic disease and is characterized by profound structural and architectural remodeling of human tissues. Here, we present a comprehensive assessment of these changes using 25,712 whole-slide histopathological images from 40 tissue types across 983 individuals in the Genotype-Tissue Expression cohort. By leveraging deep learning, we quantified nuanced morphological alterations to develop 'tissue clocks', predictors of biological age that reflect tissue structural integrity and physiological fitness. These clocks correlate with established aging markers, such as telomere attrition, subclinical pathologies and comorbidities. Through a systematic evaluation of biological aging rates across organs, we identified associations of tissue-specific age acceleration with demographic, lifestyle and medical factors, highlighting potentially modifiable risk factors that affect tissue aging. Furthermore, by integrating paired histology and transcriptomic data, we developed a strategy to predict tissue-specific age gaps directly from blood samples. We validated this approach by identifying disease-relevant organ aging across independent cohorts for eight prevalent diseases, including Alzheimer's disease, stroke and Crohn's disease. This work positions tissue architecture as a critical integrator of molecular and cellular changes over the course of aging, demonstrates that histopathological imaging provides a robust framework for monitoring tissue-specific aging and offers a scalable foundation for understanding organ-level physiological decline in health and disease.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Biorepository ; Disease ; Identification (biology) ; Dna Methylation ; License ; Pipeline (software) ; Inference ; Medline; Foundation Model; Epigenetic Age; Hypertension
ISSN (print) / ISBN 1078-8956
e-ISSN 1546-170X
Journal Nature medicine
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Research Unit Precision Regenerative Medicine (PRM)
Institute of Computational Biology (ICB)
Grants Cure Cancer Australia Foundation (CCAF)
Deutsche Krebshilfe (German Cancer Aid)
Deutsche Forschungsgemeinschaft (German Research Foundation)
Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
LEO Pharma Research Foundation
Department of Health | National Health and Medical Research Council (NHMRC)
University of Melbourne (Melbourne University)
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)