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PubMed · 42642518

Sex-specific aging clocks from a large-scale human phenome reveal distinct aging transitions and circulating signatures.

Jiaming Li·Dan-Dan Gao·Jing Li·Lei Cao·Yuanyuan Du·Muzhao Xiong·Xi Chu·Wan Lei·Wei-Dong Ye·Gang Xu·Lina Ma·Jiazhen Tang·Qing Fu·Zikai Zheng·Hongkai Zhao·Ming Yi·Chunyu Lan·Liu-Jun Xu·Yanling Fan·Guohua Zhu·Liwen Xiao·Quan Zheng·Sicong Si·Huabiao Cheng·Beier Jiang·Shuhui Sun·Wenjian Jiang·Shuai Ma·Hongjia Zhang·Si Wang·Yun-Gui Yang·Jiayin Yang·Jing Qu·Feng Zhang·Zhili Liu·Guoguang Zhao·Guang-Hui Liu·Weiqi Zhang
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Abstract

Aging is a primary risk factor for chronic diseases, yet its progression varies among individuals and between sexes. Here, under the X-Age Project, we profiled the clinical aging phenome of the Multicentric Chinese Aging Study (mCAS) through a cross-sectional analysis of 172 clinical measures from more than 100,000 participants aged 18-98 years across three centers. These profiles enabled sex-specific clinical aging clocks that revealed divergent aging trajectories between women and men during midlife that converged in later life. Phenome-wide analyses revealed age-related accumulation of metabolic factors, including low-density lipoprotein, triglycerides, glucose and uric acid, and tumor markers, such as carcinoembryonic antigen and human epithelial protein 4. These age-accumulating factors induced senescence-related phenotypes in human endothelial cells. Furthermore, a high-fat diet mouse model with dietary reversal supported the modifiability of metabolic burden-induced aging. Together, this work establishes metabolic and tumor marker accumulation as actionable drivers of human aging, paving the way for personalized, sex-stratified geroprotective interventions.

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HumansFemaleAgingAgedMiddle AgedAged, 80 and overAnimalsAdultMalePhenotypeAdolescentMiceYoung AdultCross-Sectional StudiesBiomarkersSex FactorsUric AcidDiet, High-FatJournal Article

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Jiaming Li, Dan-Dan Gao, Jing Li, Lei Cao, Yuanyuan Du, Muzhao Xiong, Xi Chu, Wan Lei, Wei-Dong Ye, Gang Xu, Lina Ma, Jiazhen Tang, Qing Fu, Zikai Zheng, Hongkai Zhao, Ming Yi, Chunyu Lan, Liu-Jun Xu, Yanling Fan, Guohua Zhu, Liwen Xiao, Quan Zheng, Sicong Si, Huabiao Cheng, Beier Jiang, Shuhui Sun, Wenjian Jiang, Shuai Ma, Hongjia Zhang, Si Wang, Yun-Gui Yang, Jiayin Yang, Jing Qu, Feng Zhang, Zhili Liu, Guoguang Zhao, Guang-Hui Liu, Weiqi Zhang. 2026-08-25. Sex-specific aging clocks from a large-scale human phenome reveal distinct aging transitions and circulating signatures.. https://doi.org/10.1038/s43587-026-01180-5

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