Age-related cognitive decline may be linked to key blood cell protein


New research published in the journal PLOS Biology is describing the discovery of a link between cognitive decline and a protein in red blood cells. The research found mice depleted of this protein suffered from rapid cognitive decline, and a potential new anti-aging therapeutic target could be possible if the same observation can be validated in humans.

“Red blood cells have an irreplaceable function to deliver oxygen to maintain bioenergetics of every single cell within our body,” explains lead author on the new study, Yang Xia. “However, their function in age-related cognition and hearing function remains largely unknown.”

The new research is based on the hypothesis that a progressive decrease in oxygen supply to tissues is a key factor in aging. Adenosine receptor A2B (ADORA2B) is a protein that aids the release of oxygen from red blood cells, and to test what effect reduced levels of this protein has on cognition, the researchers developed mouse models engineered to lack this vital protein.

Using a number of cognitive and physiological tests the animals were compared healthy mice. The mice lacking ADORA2B displayed faster declines in memory and hearing as they aged compared the control animals, and when the animals were deprived of oxygen in a simulated hypoxia scenario, this age-related cognitive decline accelerated even more rapidly.

The researchers hypothesize ADORA2B is vitally important at maintaining tissue oxygenation in the brain and as we age levels of the key protein decline. This means brain aging could potentially be slowed by finding ways to maintain levels of this protein.

The idea that decreasing tissue oxygenation plays a role in the onset of brain aging and cognitive decline is still unproven. However, this new research does offer some mechanism to explain prior studies finding transplanting blood from young mice into old mice improves cognition. The research also offers clues to explain how hyperbaric oxygen treatments can generate anti-aging effects.

“Our findings reveal that the red blood cell ADORA2B signaling cascade combats early onset of age-related decline in cognition, memory and hearing by promoting oxygen delivery in mice and immediately highlight multiple new rejuvenating targets,” adds Xia.

It is still very early days for this research avenue so don’t expect a novel anti-aging treatment to stem from these findings any time soon. There are clues that very mild oxygen deprivation occurs with aging in human brains but much more work will be needed to explore how much of a role this plays in age-related cognitive decline. It is also unclear whether modulating ADORA2B in humans is a safe or effective anti-aging therapy. But nevertheless, this new discovery offers researchers a novel pathway to explore potential anti-aging treatments in the future.

The new study was published in the journal PLOS Biology., 20 June 2021