Genetic determinants of proteomic aging.

Alexander Mörseburg, Yajie Zhao, Katherine A Kentistou, John R B Perry, Ken K Ong, Felix R Day

MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK. [email protected] Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK. [email protected]. · pubmed

Paper

Abstract

Changes in the proteome and its dysregulation have long been known to be a hallmark of aging. We derived a proteomic aging trait using data on 1459 plasma proteins from 44,435 UK Biobank individuals measured using an antibody-based assay. This metric is strongly associated with four age-related disease outcomes, even after adjusting for chronological age. Survival analysis showed that one-year older proteomic age, relative to chronological age, increases all-cause mortality hazard by 13 percent. We performed a genome-wide association analysis of proteomic age acceleration (proteomic aging trait minus chronological age) to identify its biological determinants. Proteomic age acceleration showed modest genetic correlations with four epigenetic clocks (R

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Research summary

The paper claims that proteomic age acceleration is genetically determined and correlates with increased mortality risk. This research is relevant as it investigates biological determinants of aging, contributing to the understanding of aging mechanisms and potential interventions.

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