Researchers at the University of Colorado Anschutz Medical Campus have identified a biomarker of red blood cell (RBC) and human aging that could help tailor better blood storage and transfusion strategies. Also, the discovery could potentially help combat a growing blood shortage crisis (see sidebar).
In the study, published in Aging Cell, researchers examined 15,700 blood specimens from 13,757 individuals – the largest study of how RBCs, the most numerous cells in the body, change as humans age.
Julie Reisz Haines, PhD, assistant research professor at the University of Colorado School of Medicine (SOM), led the study, which was co-authored by SOM biochemistry and molecular genetics colleagues Angelo D’Alessandro, PhD, professor, and Travis Nemkov, PhD, assistant professor.
In the study, four cohorts – including RBCs from healthy blood donors and patients with sickle cell disease – were analyzed to define age-dependent changes in RBC metabolism.
Combating a Crisis: Incentivizing Blood DonationsIn addition to personalized approaches to blood transfusions, a group of CU Anschutz researchers in the Department of Biochemistry and Molecular Genetics hope their ongoing studies into molecular-based signatures of health will help alleviate the U.S. blood shortage crisis. According to the American Red Cross, the number of people donating blood has dropped 40% over the past 20 years, and blood donors continue to skew older.The idea is to incentivize younger people to donate blood by providing useful health information – profiles of their blood’s molecular aging clock – back to the donors. Travis Nemkov, PhD, associate research professor, said, “By providing molecular-based health information to donors, we can attract more, especially younger, donors who might continue donating throughout their lives as they gain valuable insights into their health as a reward for their altruism.” |
“Blood donors are a great resource to study population health because they give us insight into how aging affects otherwise healthy people,” Reisz Haines said. “It’s like looking through a window into how the entire body is aging, rather than focusing solely on one particular illness or organ.”
Specifically, the study identified age-related alterations in the arginine pathway. This pathway involves converting arginine, an amino acid, to nitric oxide and citrulline, another amino acid shown to improve blood flow. In older individuals, arginine levels in RBCs decrease, while its metabolites such as citrulline and ornithine increase. These shifts provide a molecular signature of aging that is consistent across the different investigated cohorts, including the patients with sickle cell disease, suggesting that human aging has universal effects on RBC metabolism.
One of the study’s key discoveries was the connection between aging and the effectiveness of blood transfusions. “We found that higher levels of citrulline in donated blood units correlate to higher increases in hemogloblin (the protein in RBCs that carries oxygen to tissues and organs) in the recipients’ blood 24 hours after transfusion,” Reisz Haines said. “This suggests a better outcome from the transfusion.”
Using multiomics data, including genomics data that the CU Anschutz team and their collaborators linked with metabolite levels and blood donor demographics, researchers linked metabolism of arginine during RBC storage to increased vesiculation – a hallmark of RBC aging – and lower post-transfusion hemoglobin levels.
Additionally, the study offered insights on the potential to tailor donated blood to recipients. “We found specific genetic traits that tell whether arginine metabolism is rerouted,” D’Alessandro said. “We then showed that this metabolic pathway can serve as a marker of storage quality for the blood unit and of healthy aging of the donors.”
Red Blood Cells: Window Into HealthBlood is not only essential for life, but it’s also a powerful window into the health of the body as it ages. Red blood cells (RBC) make up 80% of human cells and every minute they travel from the heart to peripheral capillaries and back.While delivering oxygen to all organs in the body, RBCs also load and release small molecules in the process, a loop they travel 178,000 times during their average lifespan of 120 days in circulation. As a result, RBCs provide a window into the metabolism of the whole body. In addition, as humans live longer, older people are more heavily represented in the populations of blood donors and transfusion recipients. How human aging impacts the cells’ performance after transfusion is crucial for refining practices of blood transfusion and maximizing the best outcomes for recipients. |
Every donation is valuable, he said, especially as blood donations decline globally. This research highlights how understanding metabolic changes in RBCs can help improve transfusion strategies in the future, for example by modifying the solutions in which blood units are stored prior to transfusion.
In the bigger picture, D’Alessandro said, studying RBCs gives scientists greater insight into how healthy aging is a function of metabolism and genetics. “Both potentially impact everything that relies on oxygen – from responses to cancer to cardiovascular disease, from exercise performance to neurodegenerative diseases and so on,” he said.