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Genetic determinants of proteomic aging
Alexander Mörseburg1,2, Yajie Zhao3, Katherine A Kentistou3
1MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK. am2037@cam.ac.uk.
Npj Aging
|April 26, 2025
Summary
A new proteomic aging metric derived from plasma proteins is linked to age-related diseases and mortality. This proteomic age acceleration is influenced by genetics and metabolic factors like obesity and type 2 diabetes.
Area of Science:
- Proteomics
- Genetics
- Aging Research
Background:
- Proteomic changes and dysregulation are key indicators of aging.
- Existing aging biomarkers often require invasive methods or are limited in scope.
Purpose of the Study:
- To develop and validate a novel proteomic aging metric using plasma proteins.
- To investigate the association of this metric with age-related diseases and mortality.
- To identify genetic and lifestyle factors influencing proteomic aging.
Main Methods:
- Utilized plasma proteomic data from 44,435 UK Biobank participants.
- Developed a proteomic aging trait based on 1459 plasma proteins.
- Performed survival analysis, genome-wide association studies (GWAS), and Mendelian randomization (MR).
Main Results:
- The proteomic aging metric strongly correlates with age-related diseases and increases all-cause mortality risk.
- GWAS identified three key genetic loci (BRCA1, POLR2A, TET2) associated with proteomic age acceleration.
- MR analysis revealed causal links between higher BMI, type 2 diabetes, and accelerated proteomic aging.
Conclusions:
- A plasma-based proteomic aging metric serves as a robust indicator of biological aging and disease risk.
- Specific genetic variations and metabolic syndrome components significantly impact the rate of proteomic aging.
- This research provides insights into the molecular mechanisms underlying aging and age-related diseases.
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