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

Pubmed ID: 39478346

Pubmed Central ID: PMC11822668

Journal: Aging cell

Publication Date: Feb. 1, 2025

MeSH Terms: Humans, Male, Adult, Female, Aged, Aging, Middle Aged, Anemia, Sickle Cell, Animals, Mice, Erythrocytes, Biomarkers, Arginine

Grants: R01 HL126130, R01HL126130, R01 HL146442, P30 AG038070, R01 HL161004, R01HL168775, UH3HL143192, R01HL146442, R01HL098032, R01 HL168775, R01HL149714, R01HL148151, R01HL133049, UH3 HL143192, R21 HL150032, R01 HL149714, R01 HL125886, R01 HL133049, 75N92019D00033, R01 HL098032, R01HL125886, R01 HL148151

Authors: Busch MP, Gladwin MT, Kleinman S, Norris PJ, Page GP, Roubinian NH, Spitalnik SL, Hod EA, Reisz JA, Earley EJ, Nemkov T, Key A, Stephenson D, Keele GR, Dzieciatkowska M, Hansen KC, Zimring JC, Churchill GA, D'Alessandro A

Cite As: Reisz JA, Earley EJ, Nemkov T, Key A, Stephenson D, Keele GR, Dzieciatkowska M, Spitalnik SL, Hod EA, Kleinman S, Roubinian NH, Gladwin MT, Hansen KC, Norris PJ, Busch MP, Zimring JC, Churchill GA, Page GP, D'Alessandro A. Arginine metabolism is a biomarker of red blood cell and human aging. Aging Cell 2025 Feb;24(2):e14388. Epub 2024 Oct 30.

Studies:

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.