A new study from the University of California, Berkeley, found that older mice developed new muscle fibers and began to reverse aging after undergoing a plasma-thinning procedure.
At Berkeley, researchers have shown in a new study that age-reversal effects can be achieved by diluting the blood plasma of old mice, without the need for young blood (which has produced similar effects in previous studies).
In the study, the team began diluting the blood plasma of aged mice by replacing it 50% with a mixture of saline and alumina. The albumin simply replaced the proteins lost with the removal of the plasma. The result? Rejuvenation with effects on the brain, liver and muscles.
This discovery moves i dominant models to reverse aging from using young blood to removing potentially harmful aging factors from the blood.
Two hypotheses from the discovery that diluting blood rejuvenates mice
The first is that, in the mouse, rejuvenation is due to young blood carrying proteins and factors that decline with aging. The second, equally possible, is that with age some proteins in the blood become harmful. Irina Conboy, professor of bioengineering at UC Berkeley and lead author of the study, is certain. “As our science shows, the second interpretation is correct. Young blood is not needed for the rejuvenating effect: it is enough to dilute the plasma.”
Two words about plasma
In humans, the composition of blood plasma can be changed in a clinical procedure called therapeutic plasma exchange or plasmapheresis. It is a procedure currently approved by the FDA in the United States for the treatment of a variety of autoimmune diseases.
The research team is currently finalizing clinical trials to determine whether a modified plasma exchange in humans can be used to improve the overall health of older people and to treat age-associated diseases including loss of muscle mass, neurodegeneration, type diabetes 2 and immune imbalances.
The results of the study (which appears online in Aging magazine) may open the door to further research into the use of plasma exchange for both anti-aging and immunomodulation.
Aging? Transient and reversible
In the early 2000s Irina Conboy and her husband and research partner Michael Conboy had the feeling that our body's ability to regenerate damaged tissue remained alive even in old age with stem cells. Somehow, however, these cells would "turn off" with the biochemical changes due to aging.
“We had the idea that aging might be much more dynamic than people think,” Conboy said. “We thought it might be characterized by a transient and very reversible decline in regeneration. In short, a state that can be reversed by replacing deteriorated cells and tissues with healthy ones."
After the Conboys published their first, groundbreaking work in 2005, many researchers seized on the idea that specific proteins in young blood might be the key to unlocking the body's latent regenerative capabilities.
However, in the original report and in a more recent study, when blood was exchanged between young and old animals without physically joining them together, the young animals showed signs of aging. These results indicated that the “young” blood could not compete with the old blood.
Dilute the plasma to reduce harmful proteins
As a result, the Conboys pursued the idea that a accumulation of certain proteins with age was the main inhibitor of tissue maintenance and repair, and that diluting these proteins with blood exchange could be a solution.
In short, an alternative and safer path: instead of adding proteins from young blood, dilute the old plasma.
To test this hypothesis, the Conboys and their colleagues came up with the idea of performing a “neutral” blood exchange. Instead of swapping a mouse's blood for that of a younger animal, they would simply begin diluting the blood plasma with a solution containing its most basic ingredients: saline and a protein called albumin.
“We thought, 'What if we had age-neutral blood, blood that's neither young nor old?'” he says Michael Conboy. Bingo.
After finding that the neutral blood exchange significantly improved the health of the old mice, the team conducted a proteomic analysis of the animals' blood plasma to find out how the proteins in their blood changed following the procedure.
And dilute plasma in humans?
The researchers performed a similar analysis on blood plasma from humans undergoing therapeutic plasma exchange.
They found that the plasma exchange process acts almost like a molecular reset button. A “reset” button that lowers the concentration of pro-inflammatory proteins that increase with age, while allowing more beneficial proteins, such as those that promote vascularization, to rise back in numbers.
“Some of these proteins are of particular interest and, in the future, we may consider them as additional therapeutic and drug candidates,” Conboy said. “But I would like to warn against illusions of having found an elixir of life. It is very unlikely that aging can be reversed by changes in any one protein alone. In our experiment, meanwhile, we found that we can do a simple, FDA-approved procedure that steers the levels of numerous proteins in the right direction."
Therapeutic plasma exchange in humans lasts approximately 2-3 hours and has no or mild side effects.
