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

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 D'Alessandro

Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. · pubmed

Paper

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.

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Research summary

The paper investigates age-associated changes in red blood cell metabolism, specifically focusing on arginine metabolism as a potential biomarker of aging. This aligns with the exploration of molecular mechanisms underlying aging and age-related diseases, which is relevant to longevity research. However, while the findings are solid and contribute to understanding the metabolic changes associated with aging, they do not present a major breakthrough or transformative implications for the field, thus warranting a moderate impact score.

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