On August 16, Keck Graduate Institute (KGI) Associate Professor Dr. Kiana Aran and her team published a paper, "Erythrocytes, a New Contributor to Age-Associated Loss of Blood–Brain Barrier Integrity," in Advanced Science.
This article is one of the team's major papers on aging research and describes how old red blood cells from both mice and humans resulted in a leaky blood-brain barrier and allowed the passage of test molecules across the brain.
"As we age, our red blood cells morphology changes," Aran said. "They become stiffer, and it is harder for them to deform as they pass the small lumen of our capillaries. This lack of flexibility makes them experience more forces from shear stress."
Aran and her team hypothesized that this enhanced shear stress activates the nitric oxide synthase on the surface of red blood cells, generating more nitric oxide and making the blood-brain barrier leaky.
The research team also showed that inhibiting nitric oxide synthase reduced the red blood cells adverse effects on the brain's age. This was done using a unique Brain-on-a-chip device that Aran and her team developed with integrated electronics to measure the blood-brain barrier integrity.
“This is a very important finding given that red blood cells are the most prevalent cell in the blood,” said Aran. “Previously, red blood cells have not been identified as contributors to age-associated decline. With this study, we show that red blood cells may be used as a valuable therapeutic target to mitigate the effects of aging.”
These studies have paved the way for an extensive collaborative study with the UCSF Memory and Aging Center. Two of KGI’s PhD in Applied Life Sciences students, Jonalyn Herce and Payam Amiri, will be testing samples from Alzheimer’s patients to quantitatively monitor the impact of their red blood cells and other blood factors on blood-brain barrier integrity and brain health.