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Longevity Bites: Diluting Blood Plasma Reverses Ageing in Mice | Prof. Michael Conboy

23 June 2021

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Longevity bites provides short highlights from our incredible talks with some of the world’s leading scientists, researchers, and thinkers about human ageing and longevity.

A few months ago, we had the opportunity to sit down with the husband and wife team of Professor Michael and Professor Irina Conboy.

Both are Professors at the University of California, Berkeley in the Department of Bioengineering. Their discovery of the rejuvenating effects of young blood through parabiosis in a seminal paper published in Nature in 2005 paved the way for a thriving field of rejuvenation biology.

The Conboy lab currently focuses on broad rejuvenation of tissue maintenance and repair, stem cell niche engineering, elucidating the mechanisms underlying muscle stem cell ageing and making CRISPR a therapeutic reality.

In the full talk, we discussed their most recent paper “Diluting blood plasma rejuvenates tissue, reverses ageing in mice”.

Here’s what was said:

Chris: Could you please explain the methodology, and the results, of your recent research?

Michael: So parabiosis is like a Siamese twinning of the young and the old animal, and they share blood. But they also, because they’re connected for a very long time, I mean a relatively long time, they share the tissue and organ systems of the partner. So the young animal suffers half its mass, or more than half its mass, being old, and having old liver or kidneys, blah, blah, blah. The old partner gets access to a young set of liver, and kidneys, and pancreas, and insulin regulation, and digestive system, and whatever. So we didn’t know for sure if it was the effects that we saw were because of the blood or because of the other systems that kind of communicate through the blood.

The next experiment we did was that it was a blood exchange. So we just took two animals and transfused blood back and forth back and forth between them. And then after several exchanges, you approach homogeneity between them -so there’s about 50/50 – and then disconnect them. And because the only thing that was transferred was the blood, we could rule out the effects of workings and regulatory systems.

So from that work, we found that the liver was improved in the old animal, the muscle regeneration was improved, the brain wasn’t really all that improved, and the young partner that got old blood, the muscle regeneration was a little worse.The liver couldn’t really see much of a defect that the things that we looked at but their brains look like they got stupider.

So then at the end of that, we said ‘Okay, now did this happen because the old animal got an infusion of young factors, young, pro-youth factors? Or, did it see improvement because it got rid of half of its old bad factors?’

And conversely, the young animal did it get worse because it got these old factors or because it got rid of half of its good factors? So what if we could do a blood exchange like we did between the young and the old animals, but with each of them have them exchange with something that was neutral.
And we tried to figure out what age of mouse could be neutral, but it’s difficult to point to a particular age. So we said what if we just hypothesised: let’s say it’s not the red blood cells and it’s not the white blood cell – that leaves plasma. So, what if we had some blood that we throw out the plasma and replace it with purified saline and purified albumin, which is like the major ingredient in plasma, but it doesn’t have any factors in it, so it’s just devoid of factors – doesn’t have any old factors doesn’t have young factors – and do the exchange with that. Would the old animal look a little younger and would the young animal look a little older?

So that was the basis for the experiment that we did. We took old mouse blood and pelleted the red blood cells and the white blood cells and threw away the platelet rich plasma. So it’s got albumin in there, it’s got antibodies in there, it’s got platelets for clotting, and it’s got all the old factors that would be in old blood. And replace that with saline mixed in with the major purified component of blood, this albumin.

And then we did the exchange with the old mouse with that, and we did some with young mice too, so that, at the end, the old animal has all its red blood cells, and has all its white blood cells and has half of its platelets, and it has its plasma diluted in half by this purified plasma, basically.

So that technically what the experiment is and then what we found was rather surprising. I didn’t expect the old animal to be really all that much improved. I figured some things might change, but in other ways it would get worse, but it didn’t seem to get worse and pretty much everything we looked at.

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