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A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
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Ticking Differently: Elucidating Sexual Dimorphism in Human Aging through Metabolomics, Proteomics and Genomics
Sihao Xiao1,2,3, Pallavi Kaushik1, Gaoyu Du4
1Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Medrxiv : the Preprint Server for Health Sciences
|November 24, 2025
Summary
This study created a sex-specific metabolic aging clock, revealing distinct aging mechanisms in males and females. Understanding these differences is crucial for personalized health strategies and public health policies.
Area of Science:
- Gerontology
- Metabolomics
- Genetics
Background:
- Aging clocks often overlook sex-specific differences.
- Metabolic aging mechanisms vary between males and females.
Purpose of the Study:
- Develop a sex-specific metabolic aging clock.
- Identify mechanisms accelerating or decelerating metabolic aging in both sexes.
- Investigate the link between accelerated metabolic age and health outcomes.
Main Methods:
- Utilized UK Biobank data from 390,941 individuals.
- Integrated genetic, proteomic, and epidemiological data.
- Developed a sex-specific metabolic aging clock.
Main Results:
- Identified common and sex-specific metabolic aging mechanisms.
- Dysregulation in cholesterol, immunity, and cell processes accelerate aging.
- Oxidative stress, resilience, and tissue integrity decelerate aging.
- Reproductive factors like parity and age at childbirth show protective effects.
- Accelerated metabolic age predicts morbidity and mortality, with stronger associations in males.
- Obesity differentially impacts metabolic aging and disease risk between sexes.
- Accelerated metabolic aging predicts cancer in males but not females.
Conclusions:
- Metabolic aging processes exhibit significant sex differences.
- Sex-specific aging clocks are essential for understanding disease susceptibility.
- Findings highlight the need for sex-informed healthcare strategies and public health policies.
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