Arginine Metabolism is a Biomarker of Red Blood Cell and Human Aging

Overview

Journal Aging Cell

Specialties Cell Biology
Geriatrics

Date 2024 Oct 31

PMID 39478346

Authors

Julie A Reisz

Eric J Earley

Travis Nemkov

Alicia Key

Daniel Stephenson

Gregory R Keele

Monika Dzieciatkowska

Steven L Spitalnik

Eldad A Hod

Steven Kleinman

Nareg H Roubinian

Mark T Gladwin

Kirk C Hansen

Philip J Norris

Michael P Busch

James C Zimring

Gary A Churchill

Grier P Page

Angelo DAlessandro

Affiliations

Soon will be listed here.

Abstract

Increasing global life expectancy motivates investigations of molecular mechanisms of aging and age-related diseases. This study examines age-associated changes in red blood cells (RBCs), the most numerous host cell in humans. Four cohorts, including healthy individuals and patients with sickle cell disease, were analyzed to define age-dependent changes in RBC metabolism. Over 15,700 specimens from 13,757 humans were examined, a major expansion over previous studies of RBCs in aging. Multi-omics approaches identified chronological age-related alterations in the arginine pathway with increased arginine utilization in RBCs from older individuals. These changes were consistent across healthy and sickle cell disease cohorts and were influenced by genetic variation, sex, and body mass index. Integrating multi-omics data and metabolite quantitative trait loci (mQTL) in humans and 525 diversity outbred mice functionally linked metabolism of arginine during RBC storage to increased vesiculation-a hallmark of RBC aging-and lower post-transfusion hemoglobin increments. Thus, arginine metabolism is a biomarker of RBC and organismal aging, suggesting potential new targets for addressing sequelae of aging.

Citing Articles

Arginine metabolism is a biomarker of red blood cell and human aging.

Reisz J, Earley E, Nemkov T, Key A, Stephenson D, Keele G Aging Cell. 2024; 24(2):e14388.

PMID: 39478346 PMC: 11822668. DOI: 10.1111/acel.14388.

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