Saturday, April 10, 2021

Tissue Rejuvenation Via Plasma Dilution

lifespan  |  Back in 2005, Drs. Irina and Michael Conboy showed that joining the circulatory systems of young and old mice together in a procedure called parabiosis could rejuvenate aged tissues and reverse some aspects of aging in old mice.

Following this discovery, many researchers concluded that there must be something special in young blood that was able to spur rejuvenation in aged animals, and various companies have been trying to find out what. Indeed, we recently reported that researchers were apparently successful in halving the epigenetic age of old rats by treating them with Elixir, a proprietary mix of pro-youthful factors normally found in young blood.

However, a question still remains: was the rejuvenation the result of there being something beneficial in the young blood, or is it more a case of dilution of the harmful factors present in old blood?

Today, we want to spotlight a new study by Drs. Irina and Michael Conboy, which again lends more weight to the idea that the rejuvenation is most likely due to a dilution of pro-aging factors in old blood rather than there being any special sauce in young blood [1].

During the study, the research team discovered that by replacing half of the blood plasma in old mice with a saline and albumin mixture, the albumin replacing the lost protein that was removed when the original old blood plasma was taken, they could achieve a similar or even greater rejuvenation effect in brain, liver, and muscle tissues as joining two mice together through parabiosis or giving old mice young blood.

We had the opportunity to interview Drs. Irina and Michael Conboy about this new discovery and to see if we could get to the bottom of the mystery surrounding aged blood rejuvenation.

Steve: This recent paper builds on the 2015 paper of TGF beta, but it goes even further back to the days when you guys had a lab next door to Amy Wagers and Tony Wyss-Coray and you all shared the techniques, including the parabiosis technique.

Irina: Yes. Actually, I would like also to thank you, Elena, and the whole organization for highlighting our work and giving us an opportunity to speak in interviews.

Steve: You are very welcome. So, is this dilution? Is it what you put in that’s more important, is it what you take out, or is it both? I personally think that the evidence strongly suggests that it’s more what you take out, but that doesn’t necessarily mean that there isn’t good stuff in young blood.

Irina: Since our 2005 heterochronic parabiosis paper, many people jumped into this boat of young blood, thinking that the reason for rejuvenation is that there are less young factors in an old animal and we provided them. Meanwhile, all our work even leading to that paper suggested the opposite outcome: that there are excessive factors in old blood that are actually good proteins; for example, TGF beta. You cannot live without TGF beta. But, when people age, the levels of this protein become elevated, and they start doing counterproductive things for tissue repair, induce inflammation, increase fibrosis, and prevent proliferation of tissue stem cells. That was our point of view for the past 15 years, and every single paper that we published since was putting forward the general idea that it is not the young blood, it is the old blood that needs thought and attention.