YOUNG BLOOD TRANSFUSIONS — THE ELIXIR OF YOUTH?

“Young blood” transfusions are one of the current trends in regenerative medicine. According to the latest scientific discoveries, young blood might have rejuvenating properties and it could be a promising way to overcome aging.

Many researchers are trying to elucidate what are the aging factors are and how we can predict and eventually prevent age-related diseases. The decline of tissue regenerative potential is a hallmark of ageing and may be due to age-related changes in our blood. Blood not only caries cells, that transport oxygen or fight diseases, but also carries messenger factors that transport information from one cell to another, from one tissue to another. As we get older the blood changes as well, so factors that are required for the development and maintenance of tissues start to decrease, while factors involved in injuries and inflammation increase. Therefore, “young blood transfusions” might seem like an attractive treatment strategy to prevent these age-related side effects.

The term “Young blood” transfusion refers to the technique called parabiosis, in which two organisms are sutured together in such a way that they share a circulatory system [1]. The idea of refreshing old blood with new blood was pioneered by Clive McCay of Cornell University (Ithaca, New York) and dates back to the 1950s, when he stitched together the circulatory systems of an old and young mouse and found that the cartilage of the old mouse soon appeared much younger than expected [2].

It wasn’t until recently, however, that the mechanisms behind Clive McCay’s experiment were more clearly understood. Studies were not only able to confirm McCay’s findings, but also show that a transfusion of young mouse blood can improve cognition and the health of several organs in older mice [3–4].

In 2005, Thomas Rando at Stanford University, California and his team found that young blood rejuvenated the liver and skeletal stem cells of old mice, which were able to repair injured muscles as well as young mice [3].

Further progress was made into this direction, when in 2012, Amy Wagers at Harvard University showed that young blood can reverse heart decline in old mice. Her team connected the circulatory system of healthy young mice with old mice that had cardiac hypertrophy — a condition that makes the heart swell and work harder than normal to pump blood to your body. After only four weeks, the old mouse’s heart had shrunk to the same size as its younger partner. It seems that in the opposite direction-when young organisms are exposed to old blood-things don’t look that good. Studies show that the compounds in old blood appear to have a negative impact on aging. However, in this experiment, the young mouse was seemingly unaffected by the old blood, its heart not changing in size [5].

The same team has identified a protein in the blood plasma called growth differentiation factor 11 (GDF11) that appeared to fall with age. In order to prove its rejuvenating effects, old mice with enlarged hearts were treated with daily injections of GDF11 for 30 days. Their hearts decreased in size almost as much as they had in the parabiosis experiments. Moreover, GDF11 seemed to also increase the number of blood vessels and the number of stem cells in the brain [5].

Nowadays, what scientists are most excited about, is the miraculous effects that young blood seems to have on cognitive and neurological impairments. In 2014, researchers at Stanford University demonstrated that an old mouse exposed to a young environment in this revolutionary model called parabiosis, shows a younger brain that functions better. This translates into more neural stem cells, higher activity of synapses, less inflammation in the brain and improved memory [6].

These findings may have profound implications, if they can be replicated in humans. Nowadays, life expectancy has increased, however the burden of age-related cognitive decline and neurodegenerative diseases such as Alzheimer’s still represents a public health problem. Tony Wyss-Coray and his team are already investigating into replicating these results in humans, so in a few years we might be looking at improved brain abilities for older people, a decreased loss in cognition along with a better spatial orientation and increased perceptual speed [6].

Now, the final step-giving young human blood plasma to older people with a medical condition-has already begun. In October 2014, researchers at Stanford gave young blood injections to real patients with mild/moderate Alzheimer, however the results have not been published yet, as patients need to be monitored for a long period of time. Getting approval to perform this experiment in humans is relatively simple, due to the long safety record of blood transfusions, therefore we can expect more of these studies to be conducted in the years to come. Ambrosia, a start-up based in San Fransisco, is the biggest and most ambitious research undertaking to date, which offers plasma infusions at $8000 for just two litres, to anyone aged over 35 [7].

As for what the future holds, scientists are now looking into the possibility to administer GDF 11, the compound identified in young blood and thought to have rejuvenating properties, either alone or in a potentiating cocktail, to patients with coronary or neurodegenerative diseases. A non-invasive targeted delivery of the GDF11 gene to the heart using ultrasounds has already been reported, and proved to rejuvenate the aged mouse heart and protect it from ischemic events [8]. The next step would be to administer it to humans and determine whether the same effects can be achieved. Moreover, scientists believe that GDF11 is unlikely to be the only factor that keeps organs youthful, and are optimistic about identifying other factors that exert these effects.

These experiments raise the fascinating possibility that transfusion of blood or specific bloodborne factors, such as GDF11 from young humans might rejuvenate the aged human brain and heart. Taking into consideration the progress of today’s technology and the intensive research effort to extend longevity, we might be just a step away from eternal youth.

References:

1. Kamran, P., Sereti, K.-I., Zhao, P., Ali, S. R., Weissman, I. L., & Ardehali, R. (2013). Parabiosis in Mice: A Detailed Protocol. Journal of Visualized Experiments, (80). https://doi.org/10.3791/50556 
2. Clive McCay papers, #21–14–1087. Division of Rare and Manuscript Collections, Cornell University Library. Available from: http://rmc.library.cornell.edu/EAD/htmldocs/RMA01087.html (accessed on 14.10.2017). 
3. 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. https://doi.org/10.1038/nature03260 
4. Kaiser, J. (2014). Rejuvenation Factor in Blood Turns Back the Clock in Old Mice. Science, 344(6184), 570–571. https://doi.org/10.1126/science.344.6184.570 
5. Loffredo, F. S., Steinhauser, M. L., Jay, S. M., Gannon, J., Pancoast, J. R., Yalamanchi, P., et al. (2013). Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell, 153(4), 828–839. https://doi.org/10.1016/j.cell.2013.04.015 
6. Villeda, S. A., Plambeck, K. E., Middeldorp, J., Castellano, J. M., Mosher, K. I., Luo, J., Wyss-Coray, T. (2014). Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nature Medicine, 20(6), 659–663. https://doi.org/10.1038/nm.3569 
7. Silicon Valley executives are getting $8,000 BLOOD transfusions from the young in an effort to turn the clock back on ageing. Available from: http://www.dailymail.co.uk/sciencetech/article-4851074/Silicon-Valley-executives-getting-6-000-BLOOD-transfusion.html#ixzz4vUPgilmQ (accessed on 14.10.2017). 
8. Du, GQ., Shao, ZB., Wu, J. et al. (2017). Targeted myocardial delivery of GDF11 gene rejuvenates the aged mouse heart and enhances myocardial regeneration after ischemia-reperfusion injury. Basic Research in Cardiology, 112, 7. https://doi.org/10.1007/s00395-016-0593-y