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Publications

Journal Article Ppublish 2 citations

PubMed: 39478346 DOI: 10.1111/acel.14388

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

Aging Cell 24(2):e14388

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 D'Alessandro

Affiliations

  • Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
  • RTI International, Atlanta, Georgia, USA.
  • Omix Technologies Inc, Aurora, Colorado, USA.
  • Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York City, New York, USA.
  • University of British Columbia, Victoria, British Columbia, Canada.
  • Vitalant Research Institute, San Francisco, California, USA.
  • Kaiser Permanente Northern California Division of Research, Pleasanton, California, USA.
  • Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
  • Department of Medicine, University of Maryland School of Medicine, University of Maryland, Baltimore, Maryland, USA.
  • Department of Pathology, University of Virginia, Charlottesville, Virginia, USA.
  • The Jackson Laboratory, Bar Harbor, Maine, USA.

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.

MeSH

Cells, Erythrocytes, Blood, Anemia, Sickle Cell, Arginine, Aging, Biomarkers, Citrulline, Blood Cells, Quantitative Trait Loci

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