We all know the folklore: vampires rejuvenate themselves and retain their vitality by sucking the blood of the living. Is it possible that the undead may have been onto something?
Rejuvenation via “Young Blood”
Rodent studies involving blood transfusions or parabiosis – the surgical joining of two animals such that they share blood circulation – have been generating a lot of hype in the longevity field for as long as I’ve been paying attention. Several researchers over the last decade have demonstrated that exposing geriatric mice to the blood of younger animals – but not the blood of other aged animals – results in a host of health benefits to the recipient, including improvements in cognition, cardiac health, and tissue regeneration. These studies indicate that “young blood” is not only somehow distinct from “old blood,” but it is also capable of inducing rejuvenation effects when transferred to older animals. Touché, Dracula.
Industry entrepreneurs were quick to respond to these findings, and startups emerged promising customers a fountain of youth in the form of plasma transfusions from young donors. Ambrosia, the most infamous of these companies, offered this new-age vampirism at a price of $8000 per treatment before shuttering in 2019, though other startups have come forth to fill the niche.
A Dearth of Human Data
The multitude of ethical problems here are obvious, but even from a pure efficacy perspective, supporting evidence for these treatments in humans is virtually nonexistent. As I’ve discussed on various occasions with Dr. Matt Kaeberlein, mice are not humans, and interventions which work in laboratory animals often fail to yield the desired results when applied to people, especially when it comes to complex processes we have yet to fully understand – such as aging.
The few human studies that have been published on young plasma treatments have thus far been purely exploratory, generally using very small cohorts and short study durations in order to assess the safety and feasibility of such treatments rather than their efficacy. In some cases, these studies lacked placebo controls, further underscoring their preliminary nature and inability to provide meaningful information on potential benefits.
But let’s look instead at perhaps the most rigorous example of such human studies: the “Plasma for Alzheimer Symptom Amelioration” (PLASMA) crossover randomized clinical trial, conducted in collaboration with the plasma startup Alkahest. Published in JAMA Neurology in 2019, the study investigated the use of plasma from young (age 18-30) donors for treating symptoms of Alzheimer’s disease (AD). Eighteen AD patients (ages 50-90) were randomized to receive once-weekly infusions of either young plasma or saline for a period of 4 weeks, followed by a 6-week washout period and subsequent 4 weeks on the alternate treatment. The study showed no significant differences in adverse events between treatments, indicating that plasma therapy was safe and well-tolerated at least under a short-term protocol. The investigators did conduct tests for efficacy as exploratory endpoints as well, though the study had not been adequately powered for these metrics. While most results were not significant, two metrics – the Functional Activities Questionnaire and the Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory – did appear to show significant improvement following plasma treatment, which others have since interpreted as evidence in support of plasma-based treatments. However, a closer look at these results nullifies this interpretation. First, half of the AD patients in this study were not blinded to the treatment they were given, opening the door for substantial placebo effects. Second, the significance reported for these measures reflected a within-group comparison (before vs. after treatment) as opposed to a between-group comparison (plasma vs. placebo) and therefore says nothing about whether plasma “works” any better than placebo – in other words, we again have reason to suspect that the results are caused by a placebo effect. Finally, as the authors themselves note, statistical corrections for multiple testing were not applied to these metrics as they should have been.
In sum, we simply don’t have human data to give us any confidence in young plasma as an effective treatment for age-related maladies. A handful of clinical trials are currently underway or recently completed – for instance, additional Alkahest trials on the potential benefits of young plasma for AD and Parkinson’s disease (e.g., NCT03765762 and NCT03713957) and a study on the use of umbilical cord blood for treating age-related frailty (NCT02418013), and these may provide more meaningful insight into efficacy in humans. However, these studies remain fairly small and of limited duration and must still be followed by Phase III trials before experimental support for plasma treatments could reach a level required for FDA approval. Citing the lack of sufficient evidence at present, the FDA issued a warning in 2019 against transfusions for rejuvenation and treatment of age-related health issues, expressing concern that “some patients are being preyed upon by unscrupulous actors.”
Isolating the “Young” from “Young Blood”
Still, the results from mice are compelling, so with more clinical trials, is it possible that plasma transfusions could someday be approved for use in humans seeking a fountain of youth? Unlikely, but that’s not to say these results won’t lead to other human therapies. Contrary to what you might have learned from vampire films, there’s nothing magical about blood. Essentially, it’s nothing more than a collection of proteins, metabolites, cells, ions, and other substances drifting around in water. If “young blood” has anti-aging or other beneficial health effects, then those effects are caused by some definable agent or combination of agents present within that blood. By identifying and isolating those key elements, we may someday be able to create synthetic analogs capable of replicating the beneficial effects of parabiosis without a drop of blood required. Apart from circumventing certain ethical concerns, this approach might even allow for improvements upon the therapeutic benefits of parabiosis, as derivatives of the compounds of interest could be engineered to optimize stability and efficacy.
Some such compounds have already been identified by research in mice, inspiring new sets of startups focused on developing viable human therapies based on the blood-borne proteins identified through animal studies. Researchers pinpointed GDF11, for instance, as a circulating protein which, when administered in isolation, can recapitulate the effects of parabiosis on reversing cardiac hypertrophy in aged mice. The lead authors on the study have since founded Elevian, a company which aims to create and commercialize GDF11-based therapies.
Rejuvenation therapies are still premature
Even these more targeted approaches still have a long way to go before they’re ready for prime time. It’s likely that recreating the full range of transfusion benefits will require a cocktail of multiple active ingredients. We have yet to recognize all of the relevant players, let alone the potentially complex ways in which they interact with each other and with the rest of the body. From there, we’ll still need to develop formulations for delivering them in a stable and bioavailable form to recipients before finally commencing clinical trials. In short, we are several years away from FDA approval of reliable, research-backed treatments.
When it comes to the rejuvenating effects of young blood in geriatric animals, we have every reason for optimism. (I plan to discuss some of these effects and the science behind them in more detail in the future on the podcast.) By understanding the mechanisms behind the apparent benefits, we may someday develop game-changing therapies for reversing aging and treating age-related health conditions in humans – no blood-sucking required. But that day is still well into the future, and we have much to learn before we get there. Any companies suggesting otherwise are spouting fiction, and I’d put as much faith in their word as I’d put in the existence of the undead.
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