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There’s been an experimental result that medical science has known about for a long time that has shaken up our basic understanding of biology. It’s called Heterochronic Parabiosis and it’s basically hooking an old animal up to a younger one. Several existing experiments suggested that this made the old animal younger, but new research questions that concept. Given that just a few years ago there was talk that older rich people were getting young blood transfusions, it’s worth diving back into this research.

The Fountain of Youth

Scientists and entrepreneurs have been in search of the fountain of youth as long as civilizations have existed. For example, the Ancient Egyptians were obsessed with youth and an idealized version of themselves, which showed up on their coffins. Meaning you’ll never find an ancient Egyptian sarcophagus for an 80-year-old with anything other than a youthful portrayal of the deceased. In addition, pharaohs were always depicted as young and vital despite their true appearance. Meaning our quest for the old to regain youth has been around a very long time.

What the Heck is Heterochronic Parabiosis?

Parabiosis means that two animals share the same system, usually a circulatory connection. Heterochronic means different aged animals. Hence heterochronic parabiosis is hooking up two different aged animals to the same circulatory system.

This century-old experiment seemed to show that an old mouse got younger. Based on that research, I’ve blogged a few times on the idea that at some point, billionaires would be hooking themselves up to young donors to exchange their blood. For example, in 2014 a company called Ambrosia appeared to sell young blood transfusions to the elderly for $8,000 (1).

The parabiosis field was rekindled in the early 2000s by a series of published studies. For example, in 2005, older mice had better stem cell and liver function when hooked to young mice (2). A 2013 study demonstrated that parabiosis was able to reduce cardiac hypertrophy (a diseased heart) in older mice (3). Finally, a 2014 mouse study suggested that young blood injections into old mice had all sorts of positive effects including better memory and younger behaving stem cells (4).

The Recent Research

With all of this scientific hype around young blood, it was only a matter of time before some scientific team had a turn at trying to replicate these results. After all, if they hold up, then the age-old search for the fountain of youth can be called off, as this treatment is very simple. In addition, you could also see how these treatments could be abused. For example, could we find old billionaires flying into third-world countries only to be hooked up to the circulatory supply of a young person who is promised a year’s wage for their troubles?

The author of the new parabiosis study had previously published showing that this technique didn’t help the immune systems of older mice (5). In their new study, they hooked an old mouse to a young one for 3 months and measured all sorts of hormones that could indicate an improved lifespan for the old mouse (6). These critical markers didn’t change. They also measured lifespans and these didn’t change either. Meaning they could detect no increased lifespan for the older mice receiving young blood. What they did find conclusively was that the young mice paired with elderly mice aged more quickly and died earlier.

What Ever Happened to Ambrosia?

The start-up company that wanted to charge $8,000 for young blood transfusions received a 2019 FDA Warning Letter and statement from the agency that warned consumers not to receive young blood transfusions (7). A business publication later that year stated that the company had shut down operations (8). The founder at that time stated that he was starting a new company called Ivy Plasma which would provide blood plasma that wouldn’t be age-specific since the FDA considered selecting young blood for transfusion as a new drug. At the time of this writing, I could find nothing recent on Ivy Plasma.

There is another company, start-up Alkahest (named after the universal solvent from Alchemy) that is using “proprietary fractions of plasma” and claims to be in multiple phase II FDA trials for treating various diseases of aging (9). IMHO their pipeline lists 7 clinical indications in phase II trials, which is certainly ambitious and well beyond the 50 million USD funding round closed in 2020 (with only 12.5 million USD going to trials) (10). So we’ll see which of these trials are viable and which are hype, as large pharma companies are usually the only ones who can support a half dozen FDA approval trials at once.

The upshot? Will young blood or plasma treatment be a thing in the future? While the newest study didn’t focus on the rejuvenation of the brain or heart or stem cells through parabiosis, it does suggest that young blood won’t help anyone live longer. However, it does suggest that hooking an old patient up to a young person as a treatment could harm the younger individual. Hence, it’s definitely not a good idea to try parabiosis in people!

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References:

1. Science. Young blood antiaging trial raises questions. https://www.science.org/content/article/young-blood-antiaging-trial-raises-questions. Accessed 8/15/2022
2. Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005 Feb 17;433(7027):760-4. doi: 10.1038/nature03260. PMID: 15716955.
3. Loffredo FS, Steinhauser ML, Jay SM, Gannon J, Pancoast JR, Yalamanchi P, Sinha M, Dall’Osso C, Khong D, Shadrach JL, Miller CM, Singer BS, Stewart A, Psychogios N, Gerszten RE, Hartigan AJ, Kim MJ, Serwold T, Wagers AJ, Lee RT. Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell. 2013 May 9;153(4):828-39. doi: 10.1016/j.cell.2013.04.015. PMID: 23663781; PMCID: PMC3677132.
4. Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, Smith LK, Bieri G, Lin K, Berdnik D, Wabl R, Udeochu J, Wheatley EG, Zou B, Simmons DA, Xie XS, Longo FM, Wyss-Coray T. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med. 2014 Jun;20(6):659-63. doi: 10.1038/nm.3569. Epub 2014 May 4. PMID: 24793238; PMCID: PMC4224436.
5. Pishel I, Shytikov D, Orlova T, et al. Accelerated aging versus rejuvenation of the immune system in heterochronic parabiosis. Rejuvenation research 2012;15(2):239–248; doi: 10.1089/rej.2012.1331
6. Three Month Heterochronic Parabiosis Has a Deleterious Effect on the Lifespan of Young Animals, Without a Positive Effect for Old Animals” by Tatiana Yankova, Tatiana Dubiley, Dmytro Shytikov and Iryna Pishel, 22 July 2022, Rejuvenation Research. DOI: 10.1089/rej.2022.0029
7. USFDA. Statement from FDA Commissioner Scott Gottlieb, M.D., and Director of FDA’s Center for Biologics Evaluation and Research Peter Marks, M.D., Ph.D., cautioning consumers against receiving young donor plasma infusions that are promoted as unproven treatment for varying conditions. https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-and-director-fdas-center-biologics-evaluation-and-0 Accessed 8/15/2022.
8. Business Insider. The founder of a startup that charged $8,000 to fill your veins with young blood says he’s shuttered the company and started a new one. https://www.businessinsider.com/young-blood-transfusions-ambrosia-shut-down-2019-6. Accessed 8/15/2022.
9. Alkahest-A Grifols Company. https://www.alkahest.com/pipeline/clinical-progress/ Accessed 8/15/2022.
10. Fierce Biotech. Startup Alkahest inks a $50M deal for anti-aging R&D. https://www.fiercebiotech.com/partnering/startup-alkahest-inks-a-50m-deal-for-anti-aging-r-d Accessed 8/15/2022.

Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications. View Profile