bioRxivPhysiologyPreprint
The human pathome shows sex specific aging patterns post-development
M. Ben Ezra, J. B. Garbrecht, N. Rasmussen, I. Heckenbach, M. A. Petr, D. J. Bakula, L. H. Mortensen, M. Scheibye-Knudsen
Abstract
Little is known about tissue specific changes that occur with aging in humans. Using the description of 33 million histological samples we extract thousands of age- and mortality-associated features from text narratives that we call The Human Pathome (pathoage.com). Notably, we can broadly determine when pathological aging starts, indicating a sexual dimorphism with females aging earlier but slower and males aging later but faster. Using machine learning, we employ unsupervised topic-modelling to identify terms and themes that predict age and mortality. As a proof of principle, we cross reference these terms in PubMed to identify nintedanib as a potential aging intervention and show that nintedanib reduces markers of cellular senescence, reduces pro-fibrotic gene pathways in senescent cells and extends the lifespan of fruit flies. Our findings pave the way for expanded exploitation of population datasets towards discovery of novel aging interventions.
- organism: human
- assay: bulk RNA-seq
- research focus: cell type annotation
- research focus: differential expression
- approach: machine learning (classical)
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Mapping Structural Aging of Human Tissue reveals tissue-specific trajectories and coordinated deterioration
Anamika Yadav, Kyle Alvarez, … Sanju Sinha·bioRxiv·Sep 29, 2025
- Rethinking mortality rates in men and women: do men age faster?
P. Lenart, D. Kuruczova, … J. Bienertova Vasku·bioRxiv·Nov 29, 2018
- Global patterns of human ageing
Saul Newman, Simon Easteal·bioRxiv·Apr 5, 2017
- Evolution favors aging in populations with assortative mating and strong pathogen pressure
P. Lenart, J. Bienertova-Vasku, L. Berec·bioRxiv·Mar 23, 2018
- Sex- and age-differences in cellular hallmarks of aging in a species with female-biased longevity and environmental sex determination
Jamie R. Marks, Fredric J. Janzen, … Anne M. Bronikowski·bioRxiv·Dec 13, 2025
- Pan-tissue Transcriptome Analysis Reveals Sex-dimorphic Human Aging
Siqi Wang, Danyue Dong, … Zefeng Wang·eLifePeer-reviewed·Oct 3, 2025