Therapeutic plasma exchange holds promise for the treatment of age-associated diseases
A recent study shows that diluting “old” blood reverses signs of aging and rejuvenates muscle, brain, and liver tissues in old mice.
A research team at the Department of Bioengineering, University of California, Berkeley, was led to the exciting discovery that exchanging old blood plasma with saline-albumin rejuvenated the tissues of old mice. This conclusion was supported by findings using a recently developed small animal blood exchange technique to replace half of the plasma in mice with saline containing albumin. The study was led by Melod Mehdipour and overseen by Professor Irina M. Conboy; the manuscript was published on May 30, 2020, in the journal Aging .
The same research team in a 2005 study used young and old mice to make conjoined twins that shared the same blood, also known as parabiosis. Their findings suggested that the young blood rejuvenated tissues and reversed aging in the old mice . Their findings sparked numerous follow-up studies aiming to identify molecules in young blood that could reverse aging.
“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,” says Professor Irina Conboy, first author of the 2005 study and corresponding author of the 2020 study .
However, this new study shows that diluting the blood of old mice had similar age-reversing effects as young blood exchange.
In this study, the researchers diluted the blood of old mice by replacing half of the blood plasma with a mixture of saline and albumin to replace the lost liquid and protein. The diluted blood enhanced muscle repair, reduced liver adiposity and fibrosis, and rejuvenated the brain in old mice, bypassing the need for young blood transfusion .
Importantly, diluting the plasma of young mice did not impair their health, suggesting it to be a safe method to reverse aging .
“There are two main interpretations of our original experiments: 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,” says Professor Irina Conboy .
Proteomic analysis on human serum from therapeutic plasma exchange (also known as plasmapheresis), an FDA-approved intervention involving plasma replacement with a substitute similar to the plasma exchange procedure used in mice, revealed elevated levels of proteins involved in tissue maintenance and repair, as well as molecules regulating immune responses.
“I think it will take some time for people to really give up the idea that that young plasma contains rejuvenation molecules, or silver bullets, for aging,” says Dr. Dobri Kiprov, a medical director of Apheresis Care Group and a co-author of the paper. “I hope our results open the door for further research into using plasma exchange — not just for aging, but also for immunomodulation.” 
These discoveries provide strong evidence supporting that the rejuvenation potential of diluting blood is likely due to reducing the levels of age-related and potentially harmful molecules found in old blood rather than anti-aging factors in young blood. Future clinical studies are warranted to assess the ability of therapeutic plasma exchange to treat age-associated diseases and promote healthy aging in humans.