Document Type
Article
Publication Date
2-1-2025
Original Citation
Reisz J,
Earley E,
Nemkov T,
Key A,
Stephenson D,
Keele G,
Dzieciatkowska M,
Spitalnik S,
Hod E,
Kleinman S,
Roubinian N,
Gladwin M,
Hansen K,
Norris P,
Busch M,
Zimring J,
Churchill G,
Page G,
D'Alessandro A.
Arginine metabolism is a biomarker of red blood cell and human aging. Aging Cell. 2025;24(2):e14388.
Keywords
JMG, Humans, Arginine, Erythrocytes, Male, Biomarkers, Animals, Female, Aging, Mice, Middle Aged, Adult, Aged, Anemia, Sickle Cell
JAX Source
Aging Cell. 2025;24(2):e14388.
ISSN
1474-9726
PMID
39478346
DOI
https://doi.org/10.1111/acel.14388
Grant
National Institute of Aging P30AG038070 (GAC)
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.