A new study by bioengineers at the University of California (UC), Berkeley has revealed an interesting new pathway in efforts to fight off the effects of aging. The team’s research has shown how diluting the blood plasma of older mice can have a strong rejuvenation effect on tissues and organs, by reducing the concentration of inflammatory proteins that typically increase with age.
The new research builds on a study published 15 years ago, where UC Berkeley scientists Irina and Michael Conboy found that when making conjoined twins of old and young mice so they shared blood and organs, they could reverse some of the effects of aging in the older animal. This prompted a lot of research into the proteins and molecules that could be contained in the younger mouse’s blood that might function as a “fountain of youth” and might possibly be harnessed to slow or reverse aging.
All these years later, the pair are still probing the mysteries of aging and the repercussions of their groundbreaking study, but are looking at it from a slightly different angle. The researchers have been investigating the idea that rather than using the proteins and molecules from young blood, perhaps the process of aging could be slowed by cleansing the old blood of its harmful proteins and molecules.
“We thought, ‘What if we had some neutral age blood, some blood that was not young or not old?’” says Michael Conboy. “We’ll do the exchange with that, and see if it still improves the old animal. That would mean that by diluting the bad stuff in the old blood, it made the animal better. And if the young animal got worse, then that would mean that that diluting the good stuff in the young animal made the young animal worse.”
The scientists explored this idea through experiments involving treated blood plasma, where part of the animal’s blood was substituted for a special solution made of basic ingredients in saline and the protein albumin, which replaces the lost albumin proteins in the extracted blood.
This neutral blood exchange, where half of the blood plasma in older mice was swapped out for the solution, was found to significantly improve their health. The rejuvenation effects on the brain, liver and muscles were the same or stronger than in the original experiments in 2005, while the procedure was found to have no ill health effects on younger mice.
Using proteomic analysis to study the blood plasma and its contents of proteins, the team found that the process acts like a “molecular reset button.” Following the exchange, the team observed lower concentrations of pro-inflammatory proteins that increase with age, while beneficial proteins including those that promote vascularization, where able to flourish.
“There are two main interpretations of our original experiments," says Irina Conboy. "The first is that, in the mouse joining experiments, rejuvenation was due to young blood and young proteins or factors that become diminished with aging, but an equally possible alternative is that, with age, you have an elevation of certain proteins in the blood that become detrimental, and these were removed or neutralized by the young partners. As our science shows, the second interpretation turns out to be correct. Young blood or factors are not needed for the rejuvenating effect; dilution of old blood is sufficient.”
The exchange of plasma in humans is already approved in the US for treatment of some autoimmune diseases, taking two to three hours and producing mild or zero side effects. The team is now in the process of drawing up clinical trials to explore the potential of these neutral blood exchanges in older people.
“A few of these proteins are of particular interest, and in the future, we may look at them as additional therapeutic and drug candidates,” Michael Conboy says. “But I would warn against silver bullets. It is very unlikely that aging could be reversed by changes in any one protein. In our experiment, we found that we can do one procedure that is relatively simple and FDA-approved, yet it simultaneously changed levels of numerous proteins in the right direction.”
The research was published in the journal Aging.
