Excerpt of HBO's Silicon Valley episode (season 4) 'The Blood Boy'
A new scientific article on the positive effects of Parabiosis created a new fuzz around this already hot topic.
Researchers from the University of California in San Francisco found out improvement in cognition and neurogenesis in parabiosed mice to be connected with the the decrease in expression of a particular enzyme:
"Here we report that the enzyme ten eleven translocation methylcytosine dioxygenase 2 (Tet2), which catalyzes the production of 5-hydroxymethylcytosine (5hmC), rescues age-related decline in adult neurogenesis and enhances cognition in mice. We detected a decrease in Tet2 expression and 5hmC levels in the aged hippocampus associated with adult neurogenesis."
I must say that the first time I heard about Parabiosis, the centenary technique that binds the circulatory system of a young and an old animal, I was shocked. I could not see the point of stitching together veins and arteries of two animals, other than pure random curiosity to see what was going to happen, which is not exactly in accordance with good practices of regulated animal research. What a lack of imagination of me.
It turned out Parabiosis was created by the French Physiologist Paul Bert (1864) with a nobel purpose: study the natural healing powers of organisms (see this short and interesting review on the topic in Nature).
Since then, many, many research has been done on the technique (see the scientific review by Conese et al. (2017) for more detailed information) and you can even find a detailed protocol to operate the procedure
in mice . Experiments in the 1970's already suggested that parabiosis extended life spam, but it was with the advent of stem cells and its research boom that parabiosis came to the highlights in the beginning of the 2000's. Conboy et al (2005) found that "Within five weeks, the young blood restored muscle and liver cells in the older mice, notably by causing aged stem cells to start dividing again". The 'young-blood-gold-rush' had started.
In 2014, Amy Wagers, one of the authors from the early 2000's, announced in Science that they had discovered 'what' in the young blood was inducing the anti-aging effects: a protein growth factor called GDF11. However, nobody, could replicate the results of this one study. Actually, scientists at Novartis with a long history of research in GDF11, published data contradicting Wagers and showing GDF11 counterproductive effects in muscle. Wagers, of course, reaffirmed her previous findings, but not one else seems to believe or being following this lead.
The conflicting results on the active principle of young blood does refrain the interest in parabiosis itself:
"The latest advancement in anti-aging therapies hardly sounds like modern medicine at all. Ambrosia, a startup based in Monterey, California, is launching a clinical trial to inject the blood of young people into just about anyone aged 35 and up—if they’re willing to pay $8,000."
Starts this article in MIT Technology Review. If I had the money, I'd try it.
The new results from Gontier's group lack the same thing that Wagers did: independent replication! Till there, I don't think there is much to celebrate. However, Silicon Valley entrepreneurs (see also the video extract from the HBO's TV show above) are betting on it and I'm curious to see what Ambrosia's clinical trial will conclude.
I'm even more curious, though, to see how society will deal with this delicate ethical question: can we ask for young blood to live more?
Bert, P. J. 1864. Expériences et considérations sur la greffe animale. Anatomie Physiologie 1, 69–87 (1864).
Conese M, Carbone A, Beccia E, Angiolillo A. 2017. The Fountain of Youth: A Tale of Parabiosis, Stem Cells, and Rejuvenation. Open Medicine. 2017;12:376-383. doi:10.1515/med-2017-0053
Kamran P, Sereti K-I, Zhao P, Ali SR, Weissman IL, Ardehali R. 2013. Parabiosis in Mice: A Detailed Protocol. Journal of Visualized Experiments : JoVE. 2013;(80):50556. doi:10.3791/50556.
Sinha M., Jang YC., Oh J., Khong D., Wu EY., Manohar R., Miller C., Regalado SG., Loffredo FS., Pancoast JR., Hirshman MF., Lebowitz J., Shadrach JL., Cerletti M., Kim M-J., Serwold T., Goodyear LJ., Rosner B., Lee RT., Wagers AJ. 2014. Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle. Science. DOI: 10.1126/science.1251152.