There’s an idea floating around out there called “young blood” to use donations from young folks to infuse older people to reverse aging. I’m skeptical.
Imagine an old man and a teenager sitting side by side, with blood flowing from the kid to the oldster in a stab at anti-aging. Sort of like a one-way fountain of youth via blood flow…Sci-fi?
People are kind of trying it in the real world.
A self-described ‘clinical trial’ of a sort by a company called Ambrosia essentially lets you buy an infusion of a younger person’s blood in an attempt at anti-aging for $8,000.
The Rich and Famous and blood
Interested? Reportedly tech guru Peter Thiel is:
“I’m not convinced yet we’ve found a single panacea that works. It’s possible there exist single-point things that could work. I’m looking into parabiosis stuff, which I think is really interesting. This is where they did the young blood into older mice and they found that had a massive rejuvenating effect. And so that’s…that is one that…again, it’s one of these very odd things where people had done these studies in the 1950s and then it got dropped altogether. I think there are a lot of these things that have been strangely underexplored.”
The Ambrosia trial is run by Jesse Karmazin down at a clinic in Monterey, CA. It aims to test the idea that young blood can help the old or at least relatively older to fight aging. This effort has been controversial and drawn criticism, in part for the money and in part for the clinical side. For example, Amy Maxmen over at Tech Review wrote, “Several scientists and clinicians say Karmazin’s trial is so poorly designed it cannot hope to provide evidence about the effects of the transfusions.” It is also unusual for an early trial to enroll 600 participants when so little is known about an investigational approach. Why so many?
Young blood principle
The idea behind young blood helping the old fight aging has been around for a long time, recently mostly supported by studies in mice including parabiosis work (where a young and old mouse are literally sewn together so as to share a circulatory system) that reported some anti-aging effects. What about humans? Who knows? I’ve include reference to key papers at the bottom of this post. Overall, I just don’t think the data is there.
There is also concern over charging for clinical trial participation here. By charging a big fee from as many as 600 participants Ambrosia could collect nearly $5 million. My opinion is that by charging for participation, those running trials are often going to find themselves in ethically dicey territory at best. For instance, charging patients to get into stem cell trials has unfortunately become a pretty common practice by clinics selling unapproved offerings with little if any data to back them up. So far the FDA and ClinicalTrials.gov, the website hub for trials, have been unable or unwilling to reign in the problem at all.
Small, carefully controlled studies in this general area of research are justified by the intriguing mouse data. For instance, Maxmen highlights a trial by Stanford’s Tony Wyss-Coray:
“In 2014, Stanford University neuroscientist Tony Wyss-Coray demonstrated that old mice had increased neuron growth and improved memory after about 10 infusions of blood from young mice. That prompted Wyss-Coray to launch a small company, Alkahest, based in Menlo Park, California, to test transfusions of plasma from young people in the treatment of Alzheimer’s disease.”
Alkahest’s trial seeks 18 patients and charges no fee. Overall, I see that as appropriate as an initial approach.
Caution is needed
Even Wyss-Coray is cautious though:
“Like several other researchers and bioethicists, Wyss-Coray worries about the fact that Ambrosia’s trial is funded by participants rather than investors. “People want to believe that young blood restores youth, even though we don’t have evidence that it works in humans and we don’t understand the mechanism of how mice look younger,” Wyss-Coray says. “I think people are just attracted to it because of vampire stories.” He mentions a Hungarian tale of a wealthy woman who bathed in the blood of virgins to retain her youth.”
In a way that Hungarian folk story about the countess Erzsébet Báthory, sometimes referred to as Countess Dracula, resonates today. There have been rumors for years already of the rich including high-tech tycoons in Silicon Valley secretly getting all kinds of anti-aging therapies including stem cell and ‘young blood-based’ infusions. Is it all made up?
There is also debate over how young blood would work at the cellular and molecular level, with some pointing toward a specific molecule called GDF11 as the driver, while others don’t agree. Just Google “GDF11” and you’ll see the debate in the various results that pop up.
The basic science
The idea of using younger or even fetal biologics to fight aging is really catching a wave right now beyond blood too. The recent Nature paper on young brain stem cells and their exosomes specifically fighting aging threw many people into a tizzy of excitement. We should be careful in extrapolating to any possible future clinical benefits. Even more on the edge was the discussion this week of a paper on ‘young’ heart cells potentially helping aging, a finding that the senior author reportedly described using the phrase “fountain of youth”. The idea of young blood and young tissues fighting aging has permeated into pop culture too. Just take a look at this 2012 piece by Perez Hilton.
Overall, there may be some real potential here conceptually with young blood or ‘young cells’ or specific compounds from them having anti-aging properties. The data so far are promising in animals, but this is one of those cases where hype is at risk of taking over an area of translational research and many people getting hurt. Yes, let’s study this concept carefully, but in my view you shouldn’t charge for it nor expose hundreds of people to risks in a single trial with little if any human data to support it.
A link to all “young blood” titled papers in PubMed and a couple key research ones:
- Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. 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. Nat Med. 2014 May 4.
- Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Katsimpardi L, Litterman NK, Schein PA, Miller CM, Loffredo FS, Wojtkiewicz GR, Chen JW, Lee RT, Wagers AJ, Rubin LL. Science. 2014 May 9;344(6184):630-4.
Hi Paul, the scientific literature is (sometimes) better than ‘just google’:
GDF11
http://pubs.acs.org/doi/abs/10.1021/acs.biochem.7b00302
A Prodomain Fragment from the Proteolytic Activation of Growth Differentiation Factor 11 Remains Associated with the Mature Growth Factor and Keeps It Soluble.
Several potential players
http://onlinelibrary.wiley.com/doi/10.1002/pmic.201600232/abstract
A targeted proteomic assay for the measurement of plasma proteoforms related to human aging phenotypes
“Circulating polypeptides and proteins have been implicated in reversing or accelerating aging phenotypes, including growth/differentiation factor 8 (GDF8), GDF11, eotaxin, and oxytocin. These proteoforms, which are defined as the protein products arising from a single gene due to alternative splicing and PTMs, have been challenging to study. Both GDF8 and GDF11 have known antagonists such as follistatin (FST), and WAP, Kazal, immunoglobulin, Kunitz, and NTR domain-containing proteins 1 and 2 (WFIKKN1, WFIKKN2). We developed a novel multiplexed SRM assay using LC-MS/MS to measure five proteins related to GDF8 and GDF11 signaling, and in addition, eotaxin, and oxytocin.”
Thank You George !
Jon, yes, you are right. More to the point, many thousands, perhaps millions, of elderly patients have received blood transfusions from on average younger persons over many decades as a part of general transfusion medicine practice. If any anti-aging benefit of any significance occurs, it might have emerged, even phenomenological, by now. For a medical investigation of a treatment with such a long history and background, a serious investigator would begin by probing the existing medical transfusion data for at least preliminary quantitative evidence supportive of the hypothesis. Of course, such analyses might also support the null hypothesis, that although this topic may have great entertainment value and public interest, it has little if any scientific or medical value. Similarly, it is possible that such studies could prove erroneous because of all sorts of data uncertainty and investigator/subject biases. That being said, it is better science to investigate than to imagine.
Thank you, Dmitry, for the references you provided. The problems with the mouse “aging factor” studies are many, including that 1) surrogate assays for “aging” in mice are inherently biased and, even if they weren’t, might not apply to human aging/longevity; 2) the identification of responsible factors in mouse studies has similar experimental bias leading to selection of factors that, although having related effects, may not be responsible for initial observations; and 3) the factors described so far are not agents that one would want to inject into humans at high dose in pure form.
Also, list among the side effects of multiple blood transfusions iron overload and heart failure. The vampire myth has the most vulnerable organ exactly right.
This seems like it would be such a simple and inexpensive thing to test. How is it that no one has done any valid research? I have a hard time believing in 60+ years no one has followed up on it. Jeepers, what if it worked, even in some minor way!?
Unfortunately we live in a corrupt world … of course there must have been research !
The fact that it is not officially to be found, would reassure me even more that there is extreme research going on, only it’s done underground!
Not to be published !
Well, of course growth hormones, exosomes and factors that can cause accumulation of proteins (aggregates of tau, synuclein, etc) are of major importance and of course, for the latter, the factor that doesn’t allow the accumulation to persist are of profound importance and therefore scientific interest.
If the process is low risk, I don’t see a problem charging for it. Underwhelming results might offer more legitimate researchers a valuable signal that their energies and resources would be better devoted somewhere else. On the other hand, positive outcomes, even from an imperfect trial, could lead to more solid research that might otherwise never take place.
“Injecting protein, called tissue inhibitor of metalloproteases 2, or TIMP2, into elderly mice largely duplicated the beneficial effects of umbilical-cord plasma. It even restored old mice’s nesting capacity: an instinctive penchant, largely lost in old age, for using available materials, such as cotton wads supplied by the researchers, to build nests in which mice typically prefer to sleep. But older mice that were given human cord plasma depleted of TIMP2 derived no learning and memory benefits. And administering TIMP2-neutralizing antibodies to young normal mice, who ordinarily perform well on memory tests, obliterated their prowess.” https://medicalxpress.com/news/2017-04-protein-human-umbilical-cord-blood.html
Yousef has found that the amount of a protein called VCAM1 (vascular cell adhesion molecule 1 or CD106) 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. When the mice were given this antibody to VCAM1 before or at the same time as old blood, they were protected from its harmful effects (https://www.newscientist.com/article/2118105-antibody-can-protect-brains-from-the-ageing-effects-of-old-blood/). Previously, this effect was found for chemokine eotaxin-1 encoded by CCL11 gen (targeting with Bertilimumab or Omalizumab) and β2-microglobulin (B2M), a component of major histocompatibility complex class 1 (MHC I) http://www.nature.com/nm/journal/v21/n8/full/nm.3898.html
Thanks, Dmitry. Helpful points and links.
Thank You Dmitry !