Blood plasma dilution

In 2005, UC Berkeley researchers discovered that conjoining young and old mice, allowing them to share blood and organs, rejuvenated tissues and reversed signs of aging in the older mice. This led to a surge in research to find "fountain of youth" proteins or molecules in young blood. However, a new study by the same team has found that simply diluting the blood plasma of old mice has similar age-reversing effects without the need for young blood.

The researchers replaced half of the old mice's blood plasma with a saline and albumin mixture. Albumin was used to replace lost proteins from the original blood plasma. This dilution method resulted in rejuvenation effects on the brain, liver, and muscle, similar to or stronger than those observed when old mice were paired with young mice or when young blood was exchanged. The procedure had no detrimental effects on young mice.

This discovery changes the dominant model of rejuvenation from focusing on young blood to the benefits of removing age-elevated and potentially harmful factors in old blood. The research supports the idea that detrimental proteins in blood elevate with age, and these proteins can be removed or neutralized by dilution.

Therapeutic plasma exchange, or plasmapheresis, a procedure that alters blood plasma composition, is already FDA-approved for treating various autoimmune diseases in the US. The research team is finalizing clinical trials to determine if a modified plasma exchange could be used to improve overall health in older people and treat age-associated diseases, such as muscle wasting, neuro-degeneration, Type 2 diabetes, and immune deregulation.

The Conboys, the researchers behind the study, initially hypothesized that the body's ability to regenerate damaged tissue through stem cells remains with us in old age but becomes dormant due to biochemical changes. Their 2005 work on conjoined mice led many researchers to believe that specific proteins in young blood were the key to unlocking latent regeneration abilities.

However, further experiments showed that young blood could not compete with old blood, leading the Conboys to explore the idea that diluting age-elevated proteins could rejuvenate tissues. Their "neutral" blood exchange experiment, which involved diluting blood plasma with saline and albumin, significantly improved the health of old mice. Proteomic analysis of the blood plasma revealed that the plasma exchange acted like a molecular reset button, lowering pro-inflammatory proteins and increasing beneficial proteins.

Therapeutic plasma exchange in humans takes about two to three hours and usually has no or mild side effects. The research team is now preparing to conduct clinical trials to better understand how therapeutic blood exchange might be applied to treat human aging-related ailments.