Research spawned by heterochronic parabiosis studies, in which an old and a young animal have their circulatory systems linked, continues to provide surprises. There is considerable debate over whether helpful factors in young blood versus a dilution of harmful factors in old blood provide the majority of the benefits to the older animal, with the evidence favoring the latter at the present time. Dilution of blood plasma has been shown to produce benefits in animal studies, but that involves adding albumin to avoid diluting that essential protein. Researchers recently showed that adding recombinant albumin, and skipping the dilution, still produces benefits to health in animal studies. This may change the understanding of what is going on here yet again.
Last year, two self-described "biohackers" in Russia had themselves hooked up to blood collection machines that replaced approximately half of the plasma coursing through their veins with salty water. Three days later, the men tested their blood for hormones, fats and other indicators of general well-being. The procedure, it seemed, had improved various aspects of immunity, liver function and cholesterol metabolism.
Irina and Michael Conboy initially tried taking the reductionist drug development approach. They identified two biochemical pathways implicated with aging, pharmacologically recalibrated both in old mice, and found that the animals' brains, livers and muscles showed signs of rejuvenation. But a more rudimentary intervention they tried did better still. In a series of experiments that inspired the Russian biohackers, the Conboys simply replaced half of the animals' plasma with saline. (They, like the biohackers, also added back albumin, a protein essential for maintaining the proper fluid balance in the blood.) The dilution of pro-aging factors proved sufficient to activate a series of molecular changes in the mice that unleashed age-defying factors, leading to cognitive improvements and reduced inflammation in the brain.
Although other researchers saw many of the same effects when they administered young blood to mice, Irina Conboy suspects that those benefits had more to do with the dilution of old plasma than any enrichments provided by the young plasma. On balance, her research suggests that the detrimental effects of circulatory proteins in old blood - which include the suppression of youthful factors - are far stronger than any rejuvenating qualities of molecules added via young blood.
Many age-elevated factors have been identified, but finding drugs for each one is a challenge. Plasma dilution, by comparison, knocks them all down - and others as yet unknown - in one fell swoop. The Conboys founded a company to develop the plasma exchange strategy further. Others feel similarly dubious about young blood as a therapeutic. "This approach reminds me of trying to refresh sour milk by pouring fresh milk into it," says Iryna Pishel, who previously tested the anti-aging effects of young plasma on old mice and saw little impact on lifespan or immunological markers of aging.