Anti-aging Protein in Blood Cells Helps Slow Cognitive Decline

As life expectancies around the world increase, so are the number of people who will experience age-related cognitive decline. The amount of oxygen in the blood declines with age. Aging in the brain might be naturally held at bay by adenosine receptor A2B (ADORA2B), a protein on the membrane of red blood cells which is known to help release oxygen from the blood cells so it can be used by the body.

Aging in the brain is naturally reduced by ADORA2B, which helps get oxygen to the brain when needed. Further testing will be needed to determine whether ADORA2B levels naturally decline with age and whether treatment with drugs that activate ADORA2B can reduce cognitive decline in normal mice.

PLOS Biology – Erythrocyte adenosine A2B receptor prevents cognitive and auditory dysfunction by promoting hypoxic and metabolic reprogramming

Hypoxia drives aging and promotes age-related cognition and hearing functional decline. Despite the role of erythrocytes in oxygen (O2) transport, their role in the onset of aging and age-related cognitive decline and hearing loss (HL) remains undetermined. Recent studies revealed that signaling through the erythrocyte adenosine A2B receptor (ADORA2B) promotes O2 release to counteract hypoxia at high altitude. However, nothing is known about a role for erythrocyte ADORA2B in age-related functional decline. Here, we report that loss of murine erythrocyte–specific ADORA2B (eAdora2b−/−) accelerates early onset of age-related impairments in spatial learning, memory, and hearing ability. eAdora2b-/- mice display the early aging-like cellular and molecular features including the proliferation and activation of microglia and macrophages, elevation of pro-inflammatory cytokines, and attenuation of hypoxia-induced glycolytic gene expression to counteract hypoxia in the hippocampus (HIP), cortex, or cochlea. Hypoxia sufficiently accelerates early onset of cognitive and cochlear functional decline and inflammatory response in eAdora2b−/− mice. Mechanistically, erythrocyte ADORA2B-mediated activation of AMP-activated protein kinase (AMPK) and bisphosphoglycerate mutase (BPGM) promotes hypoxic and metabolic reprogramming to enhance production of 2,3-bisphosphoglycerate (2,3-BPG), an erythrocyte-specific metabolite triggering O2 delivery. Significantly, this finding led us to further discover that murine erythroblast ADORA2B and BPGM mRNA levels and erythrocyte BPGM activity are reduced during normal aging. Overall, we determined that erythrocyte ADORA2B–BPGM axis is a key component for anti-aging and anti-age–related functional decline.

Artificial Red Blood Cells

Nextbigfuture notes that Robert Freitas proposed the artificial red blood cell in 1998. There has been recent work creating artificial red blood cells. Respirocytes are hypothetical, microscopic, artificial red blood cells that are intended to emulate the function of their organic counterparts, so as to supplement or replace the function of much of the human body’s normal respiratory system. Respirocytes were proposed by Robert A. Freitas Jr in his 1998 paper “A Mechanical Artificial Red Blood Cell: Exploratory Design in Medical Nanotechnology.

Freitas proposed a spherical robot made up of 18 billion atoms arranged as a tiny pressure tank, which would be filled up with oxygen and carbon dioxide.

Hypothesized Structure of a Respirocyte

In Freitas’ proposal, each respirocyte could store and transport 236 times more oxygen than a natural red blood cell, and could release it in a more controlled manner. Freitas has also proposed “microbivore” robots that would attack pathogens in the manner of white blood cells.

Recent Artificial Red Blood Cell Work

ACS Nano (2020)“Biomimetic Rebuilding of Multifunctional Red Blood Cells: Modular Design Using Functional Components”.

Researchers reporting in ACS Nano have made synthetic red blood cells that have all of the cells’ natural abilities, plus a few new ones.

The researchers made the synthetic cells by first coating donated human RBCs with a thin layer of silica. They layered positively and negatively charged polymers over the silica-RBCs, and then etched away the silica, producing flexible replicas. Finally, the team coated the surface of the replicas with natural RBC membranes. The artificial cells were similar in size, shape, charge and surface proteins to natural cells, and they could squeeze through model capillaries without losing their shape. In mice, the synthetic RBCs lasted for more than 48 hours, with no observable toxicity. The researchers loaded the artificial cells with either hemoglobin, an anticancer drug, a toxin sensor or magnetic nanoparticles to demonstrate that they could carry cargoes. The team also showed that the new RBCs could act as decoys for a bacterial toxin. Future studies will explore the potential of artificial cells in medical applications, such as cancer therapy and toxin biosensing.

People With Advanced Leukemia Need 1-3 Units of Blood Every Week

There should be constant monitoring of oxygenation levels for all people over the age of 50 and mass production of artificial red blood cells. There should be a higher standard of acceptable oxygenation levels in order to prevent and slow cognitive decline.

Advanced aging causes reduced oxygenation levels and accelerate the body’s decline. Reduced oxygenation and reduced red blood cell functions could be classified as pre-leukemia. Pre-leukemia should be treated as a medical condition.

Artificial blood production levels need to be increased to around two to ten billion units of blood per day. This level could be reduced if the artificial blood could remain in the human body for longer periods and based on how long oxygenation levels can be supported.

Maintaining oxygenation levels also improves the energy level of older people.

Oxygenation Levels

Blood oxygen levels (arterial oxygen) indicate the oxygen levels present in the blood that flows through the arteries of the body. An ABG test uses blood drawn from an artery, where the oxygen and carbon dioxide levels can be measured before they enter body tissues.

Hyperoxemia is generally detected using ABG testing and is defined as blood oxygen levels above 120 mmHg.
* Normal arterial oxygen pressure (PaO2) measured using the arterial blood gas (ABG) test is approximately 75 to 100 millimeters of mercury (75-100 mmHg).
* When the level goes below 75 mmHg, the condition is generally termed as hypoxemia.
* Levels under 60 mmHg are considered very low and indicate the need for supplemental oxygen. Supplemental oxygen is provided through an oxygen cylinder that is connected to the nose via a tube, with or without a mask.

What should oxygen levels be?

Blood oxygen levels can also be measured using an instrument known as a pulse oximeter.

The normal oxygen levels in a pulse oximeter usually range from 95% to 100%. Blood oxygen levels below 90% are considered low (hypoxemia).

SOURCES -ACS Nano, Wikipedia -Freitas, PLOS Biology
Written By Brian Wang,

14 thoughts on “Anti-aging Protein in Blood Cells Helps Slow Cognitive Decline”

  1. I was thinking it was more of a mechanical thing going on with the heart, arteries and lungs rather than anything the red blood cells do themselves. What I was thinking is that the lungs don't fully fill with air when we don't feel we need to but the blood is still pumping through our lungs.
    If we don't get more oxygen by breathing more deeply, why would we breathe more deeply when exercising?
    Yes, I am just reasoning…and that can certainly result in error.
    Maybe we are breathing more because more blood is moving faster.
    I guess we are in need of the opinion of an expert.
    I searched around for an answer, and did not find one. However, I did find this "Because each molecule of hemoglobin contains four globins, it can carry up to four molecules of oxygen." 
    And I also read that each red blood cell has approximately 270 million hemoglobin molecules. That suggests that at least mechanically it is possible for a red blood cell to carry a variable amount of oxygen.

  2. The one that makes me the most envious is the one that lets people get a full rested night's sleep in 5 hours, and they have a good memory function, and are upbeat as well. 2-3 extra hours in each day is like gaining a healthy decade. And it is less time that has to be used doing daily monotony stuff, as each day only has so much of that. It is time you can do what you want with. It is decade that is not decrepit or diminished. It is time you can use to excel in school and get a good job, or a thousand other things…other than running the vacuum, power saw or the mower at 3 AM:

  3. Having more red blood cells does not necessarily help, if this is a receptor issue. 
    In fact, If you have more red blood cells, the amount of oxygen that each carries may be reduced, as less oxygen is being asked for. And if they carry less, it may be more difficult for cells to grab that oxygen from the red blood cells.

  4. There were nootropics that in studies in the 1980s demonstrated reduced brain damage by hypoxia in animals. I think L-Deprenyl was one of the these. Vinpocetine, I think was another. It would be interesting to see if low doses of these or others could prevent some aspects of age related cognitive decline.

    Also, there have been some interesting effects shown with hyperbaric chamber use.

    I have been thinking about making one from a 500/1,000 gallon propane tank.

  5. Agree with concept of micro-artificial components injected and harmlessly discharged for augmenting various respiration, circulation, immune-related functions, etc. Would the FDA regulate this?

  6. To be honest, I have acute injury now, so this *was* to swim underwater as many times as possible, full O2 recharge with heavy breathing each time, the length each time, until exhausted. Running just breathe thru nose, which for me is quite a restriction, for warm up mile or so. edit: And, I would make it a point to eat right before running, unless the supplement I was trying indicated otherwise. Eating before running is *bad* because it puts a dual demand on the blood supply. So, hummmm?

  7. Is that just holding your breath while you exercise? Or do you use something more sophisticated like a restriction mask?

  8. I run and swim with limited breathing, to warm up at least. My red cell count is borderline abnormal high. On a related note, NASA should be interested in birth hypoxemia trauma that may be triggered into some sort of panic attack if the air starts leaking out. Other Space triggers that resemble the birth environment are micr0g/floating in the fluid, bright sunlight/lights at birth, confinement, both psychological and physical, on and on.

  9. So I'm understanding that EPO isn't JUST for high school athletics any more, it's also a nootropic for anyone over 60.

  10. The closest thing to a Jungian archetype is repressed birth hypoxemia, as it is so common and so serious. Nic addiction and other problems ensue, in all likelihood into old age. Without Primal therapy, that is.

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