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The human pathome shows sex specific aging patterns post-development

Michael Ben Ezra, Jonas Bach Garbrecht, Nasya Rasmussen, Indra Heckenbach, Michael A. Petr, Daniela Bakula, Laust Mortensen, Morten Scheibye-Knudsen
doi: https://doi.org/10.1101/2023.02.27.530179
Michael Ben Ezra
1Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen
2Methods and Analysis, Statistics Denmark
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  • For correspondence: mbenezra@sund.ku.dk mscheibye@sund.ku.dk
Jonas Bach Garbrecht
1Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen
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Nasya Rasmussen
1Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen
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Indra Heckenbach
1Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen
3Tracked.bio
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Michael A. Petr
1Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen
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Daniela Bakula
1Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen
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Laust Mortensen
2Methods and Analysis, Statistics Denmark
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Morten Scheibye-Knudsen
1Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen
3Tracked.bio
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  • For correspondence: mbenezra@sund.ku.dk mscheibye@sund.ku.dk
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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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://pathoage.com/

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 27, 2023.
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The human pathome shows sex specific aging patterns post-development
Michael Ben Ezra, Jonas Bach Garbrecht, Nasya Rasmussen, Indra Heckenbach, Michael A. Petr, Daniela Bakula, Laust Mortensen, Morten Scheibye-Knudsen
bioRxiv 2023.02.27.530179; doi: https://doi.org/10.1101/2023.02.27.530179
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The human pathome shows sex specific aging patterns post-development
Michael Ben Ezra, Jonas Bach Garbrecht, Nasya Rasmussen, Indra Heckenbach, Michael A. Petr, Daniela Bakula, Laust Mortensen, Morten Scheibye-Knudsen
bioRxiv 2023.02.27.530179; doi: https://doi.org/10.1101/2023.02.27.530179

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