Journal article
Histological aging signatures for monitoring tissue-specific aging and disease
Nature Medicine, Vol.Advanced access
14-Aug-2026
PMID: 42601488
Appears in Cancer Research Cluster Research Collection
Abstract
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.
Details
- Title
- Histological aging signatures for monitoring tissue-specific aging and disease
- Authors
- Ernesto Abila - Austrian Academy of SciencesIva Buljan - Austrian Academy of SciencesYimin Zheng - Austrian Academy of SciencesLisa Kleissl - Medical University of ViennaSigrid Klotz - Medical University of ViennaTamas Veres - Austrian Academy of SciencesZhilong Weng - University Hospital CologneMaja Nackenhorst - Medical University of ViennaRizqah Kamies - Helmholtz MunichAnja Michl - Helmholtz MunichSafwen Kadri - Helmholtz MunichSamir Moustafa - University of ViennaWolfgang Hulla - Fachhochschule Wiener NeustadtMatthias Perkonigg - Innsbruck Medical UniversityMathias Drach - Medical University of ViennaPhilipp Tschandl - Medical University of ViennaBarbara Sterniczky - Medical University of ViennaMatthias Heinig - Helmholtz MunichLaurens J De Sadeleer - KU LeuvenWim Wuyts - KU LeuvenBart Vanaudenaerde - KU LeuvenLaurens J Ceulemans - Universitair Ziekenhuis LeuvenDaniel D Buchanan - The University of MelbourneLochlan J Fennell - University of the Sunshine CoastGeorg Stary - Austrian Academy of SciencesYuri Tolkach - University Hospital CologneAdelheid Wöhrer - Innsbruck Medical UniversityHerbert B Schiller - Helmholtz MunichAndré F Rendeiro (Corresponding Author) - Ludwig Boltzmann Institute for Age Research
- Publication details
- Nature Medicine, Vol.Advanced access
- Publisher
- Nature Publishing Group
- DOI
- 10.1038/s41591-026-04566-5
- ISSN
- 1546-170X
- PMID
- 42601488
- Copyright note
- This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
- Data Availability
- See article for data availability.
- Grant note
- The A.F.R. group was supported by Angelini Ventures S.p.A. and funded by the European Research Council under the European Union’s Horizon Europe research and innovation program (101220825). The GTEx project was supported by the Common Fund of the Office of the Director of the National Institutes of Health and by the National Cancer Institute; National Human Genome Research Institute; National Heart, Lung and Blood Institute; National Institute on Drug Abuse; National Institute of Mental Health and National Institute of Neurological Disorders and Stroke. Z.W. received financial support through the German Cancer Aid (70116893). H.B.S. received funding from the Helmholtz Association and the German Center for Lung Research (DZL). L.J.C. is a senior clinical investigator for the Research Foundation, Flanders (FWO; 18E2B24N). D.D.B. was supported by a University of Melbourne Dame Kate Campbell fellowship. L.J.F. was supported by Cure Cancer Australia (CCAF-2024 Fennell). G.S. received funding from the FWF Austrian Science Fund (PAT 8019123) and LEO Foundation (LF-OC-24-001518). Y.T. received financial support through the German Cancer Aid (70116893) and the Germany Research Society (DFG; 1316/1-1). A.W. received financial support through the Vienna Science and Technology Fund (WWTF; LS20-034) and the Ludwig Boltzmann Clinical Research Group ATTRACT.
- Organisation Unit
- School of Health - Biomedicine; Cancer Research Cluster
- Language
- English
- Record Identifier
- 991250587302621
- Output Type
- Journal article
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