Arginine Metabolism in Red Blood Cells Changes with Age
Red blood cells are an underrepresented area of study when it comes to omics data, as these cells eject their nucleus and organelles when they are formed from hematopoietic progenitor populations. They do not synthesize proteins and have no gene expression to study. Nonetheless, there is still a lot biochemistry going on in there. Here researchers take a look at some of that red blood cell biochemistry, and find characteristic changes with age in arginine metabolism. Pulling on that thread may lead to a novel measure of biological age, or perhaps a way to influence some of the downstream consequences of aging on red blood cell function.
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.