Peer-Reviewed Publication
Nat Med2026September 16, 2026Journal Article
Sex-specific biological aging clocks across organs and omics.
, Zhiyuan Song1, Derek Feng1, Naowal Azraf Rahman1, Michael R Duggan2, Qu Tian2, Jian Zeng3, Xia Zhou4, Chunrui Zou1, Michael S Rafii5, Li Shen6, Paul Thompson7, Eleanor M Simonsick2, Keenan A Walker2, Andrew Zalesky8, Christos Davatzikos9, Paul Aisen5, Luigi Ferrucci2, Susan M Resnick2, Junhao Wen10,11,12,13,14
1Laboratory of AI and Biomedical Science (LABS), Columbia University, New York, NY, USA.
2Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
3Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
4Department of Computer Science, Columbia University, New York, NY, USA.
5Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, CA, USA.
6Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
7Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
8Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia.
9Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for AI and Data Science for Integrated Diagnostics (AI2D), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
10Laboratory of AI and Biomedical Science (LABS), Columbia University, New York, NY, USA. junhao.wen89@gmail.com.
11Department of Computer Science, Columbia University, New York, NY, USA. junhao.wen89@gmail.com.
12Department of Radiology, Columbia University, New York, NY, USA. junhao.wen89@gmail.com.
13Department of Biomedical Engineering, Columbia University, New York, NY, USA. junhao.wen89@gmail.com.
14New York Genome Center (NYGC), New York, NY, USA. junhao.wen89@gmail.com.
Abstract
Sex differentially shapes aging, neurodevelopment and neurodegenerative diseases such as Alzheimer's disease (AD). However, most biological aging clocks (artificial intelligence-predicted age minus chronological age) were trained on sex-pooled samples and implicitly assume sex invariance.Here we developed 38 sex-specific biological aging clocks across 15 organ systems. We first demonstrate the imp…
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