Sex-specific biological aging clocks across organs and omics

Z. Song, D. Feng, N. A. Rahman, M. R. Duggan, Q. Tian, J. Zeng, X. Zhou

1. 01

   38 sex-specific biological aging clocks developed across 15 organ systems

2. 02

   Sex-stratified training is required to build sex-appropriate healthy normative references

3. 03

   Mendelian randomization shows organ-specific aging liability is configured differently in females and males

4. 04

   Proteomics identifies distinct organ-resolved synaptic, immune, vascular and metabolic networks by sex

5. 05

   Clocks predict systemic disease and all-cause mortality in a sex- and organ-dependent manner

6. 06

   Brain aging clock shows sex-dependent association with cognitive decline trajectory in a preclinical AD trial

Study Design

Cohort Study

Sample Size

Not reported

Study Duration

Longitudinal survival follow-up across contributing cohorts

Methodology

Development of 38 sex-stratified AI-based biological aging clocks (predicted age minus chronological age) spanning 15 organ systems, with genetic parameter estimation, Mendelian randomization, organ-resolved proteomic network analysis and longitudinal survival analysis; validated against cognitive decline trajectory in a preclinical Alzheimer disease clinical trial.

Limitations

Observational; the clocks are risk-stratification tools, not validated intervention endpoints. Normative references are cohort-specific and may not transfer to other populations. Not a clinically available test. The authors note sex-pooled and sex-interaction models retain value, so this does not invalidate existing pooled clocks - it shows they obscure sex-dependent signal.