There has been a lot of hype and hope over transfusing old people with young blood in an attempt to rejuvenate the body in a similar manner to earlier heterochronic parabiosis experiments, in which the circulatory systems of an old and a young mouse were linked and some level of rejuvenation was observed [1].
Many researchers initially thought that the positive results in these tests were due to there being pro-youthful signals in the young blood. However, more recent research suggests that the possible reason is the dilution of pro-aging factors present in the old blood rather than there being any “secret sauce” in young blood.
Indeed, various studies have shown that pro-aging factors already present in the aged blood are responsible for loss of tissue regeneration and stem cell function, and inhibiting or removing these factors has induced some level of tissue regeneration [2, 3] and cognitive improvement [4]. This has lead some to search for the special ingredient in young blood that was causing the rejuvenating effect, but the solution may be even simpler.
We might be able to filter aged bloodRecent research suggests that it isn’t what you put in that makes the difference; it’s what you remove that counts [5]. Indeed, the team led by Irina Conboy at UC Berkeley is now working on a device that can filter out high levels of pro-aging signals from old human blood and resetting them to more youthful levels.
In The Guardian, Irina Conboy said:
If you can remove key inhibitor molecules from the blood of an old person and then return that blood into them, that could be immediately therapeutic. We are developing ideas for clinical trials to see what happens if you normalize levels of one key protein we think is inhibitory. We hope to start in six months and have results in three years. Right now our health declines after about seven decades. We are pretty much hoping to extend the productive plateau, where you’re not necessarily the world champion in swimming or running marathons, but you can continue for a few more decades without any critical illnesses.
Adding further weight to the dilution effect, recently, Hanadie Yousef at Stanford University in California, who has worked with Irina Conboy in the past, seems to have identified a protein that is causing some of the damage and has developed a way to block it.
The effects of blood on ageing were first discovered in experiments that stitched young and old mice together so that they shared circulating blood. Older mice seem to benefit from such an arrangement, developing healthier organs and becoming protected from age-related disease. But young mice aged prematurely. Such experiments suggest that, while young blood can be restorative, there is something in old blood that is actively harmful. Now researchers seem to have identified a protein that is causing some of the damage, and have developed a way to block it. The researchers found that the amount of a protein called VCAM1 in the blood increases with age. In people over the age of 65, the levels of this protein are 30 per cent higher than in under-25s. To test the effect of VCAM1, researchers injected young mice with blood plasma taken from older mice. Sure enough, they showed signs of ageing: more inflammation in the brain, and fewer new brain cells being generated, which happens in a process called neurogenesis. Blood plasma from old people had the same effect on mice. When researchers injected plasma from people in their late 60s into the bodies of 3-month-old mice – about 20 years in human terms – the mice’s brains showed signs of ageing. These effects were prevented when researchers injected a compound that blocks VCAM1. When the mice were given this antibody before or at the same time as old blood, they were protected from its harmful effects. Some teams have begun giving plasma from young donors to older people, to see if it can improve their health, or even reduce the effect of Alzheimer’s disease. But for the best chances of success, we’ll also need to neutralise the damaging effects of old blood. Other researchers comment that it is “surprising that a single protein seems to have such a huge effect,” but the results need to be replicated by another lab. A drug that protects people from the effects of old blood would be preferable to plasma injections. Should transfusions from young donors turn out to be effective, it would be difficult to scale this up as a treatment for all. Drugs that block harmful proteins in our own blood would be cheaper, safer and more accessible. Source: Newscientist
Conclusion
It seems that filtering out pro-aging factors might be the optimal approach here, and, hopefully, Irina Conboy will get the results we are hoping for, opening up the door for true rejuvenation of aged tissues.
Literature[1] Conboy, I. M., & Rando, T. A. (2012). Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches. Cell Cycle, 11(12), 2260-2267.
[2} Conboy, I. M., Conboy, M. J., Wagers, A. J., Girma, E. R., Weissman, I. L., & Rando, T. A. (2005). Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature, 433(7027), 760-764.
[3] Yousef, H., Conboy, M. J., Morgenthaler, A., Schlesinger, C., Bugaj, L., Paliwal, P., … & Schaffer, D. (2015). Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal. Oncotarget, 6(14), 11959.
[4] Smith, L. K., He, Y., Park, J. S., Bieri, G., Snethlage, C. E., Lin, K., … & Wheatley, E. G. (2015). [beta] 2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis. Nature medicine, 21(8), 932-937.
[5] Rebo, J., Mehdipour, M., Gathwala, R., Causey, K., Liu, Y., Conboy, M. J., & Conboy, I. M. (2016). A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood. Nature Communications, 7.
