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Summary: A recently announced parabiosis trial in humans – the practice of transfusing young blood to old – may have profound implications for treating the chronic diseases of old age, including metabolic changes, frailty, Alzheimer’s, Parkinson’s, and other forms of dementia. However, some geroscientists say that variations of the procedure could cause severe side effects. [This article first appeared on the website LongevityFacts.com. Author: Brady Hartman. ]

The idea that youthful blood might rejuvenate our aging bodies has lingered in the popular imagination for centuries, fueled by recent experiments in which these transfusions revitalized aging mice.

Last week, Bill Faloon of the Life Extension Foundation (LEF) in partnership with the Young Blood Institute (YBI), announced a bold new human trial of the rejuvenating effects of the young blood / old blood swap, saying

“A new human rejuvenation research project is being spearheaded in Palm Beach County.” Adding “Bill Faloon and Mark Urdahl from the Young Blood Institute will announce this new clinical trial model whereby old blood plasma will be removed via blood cell separation technology while simultaneously infusing healthy young plasma factors.”

Parabiosis experiments demonstrate the rejuvenating properties of young blood – a bizarre procedure in which doctors surgically join two mice, allowing them to share the same circulatory system. With the young blood flowing through the old mouse’s veins and vice-versa, the old mouse becomes rejuvenated, while the young mouse grows more lethargic.

Scientists have discovered two ways to reap the rejuvenation benefits of parabiosis:

Plan A – is classical parabiosis modeled after the mice experiments, in which whole young blood or blood plasma is transfused into aging patients.

Plan B – is a fancy type of blood purification, akin to plasmapheresis, in which technicians remove pro-aging factors from old blood and return it to the aging donor.

Plan B – the LEF-YBI Experiment

Details of the trial are sketchy, however, here is what is known. LEF-YBI announced that they plan to recruit 30 study participants over the age of 50, with no upper age limit. The LEF-YBI trial has elements of plan A in which technicians will remove blood from the study participants and clean the blood to be cycled back into the subject. It is not entirely clear if the participants will receive plasma components from younger donors, along the lines of plan A, a practice that could carry severe side effects. The treatment consists of 6 plasma transfusions scheduled over 5 weeks that aim to “remove senile proteins while simultaneously transfusing healthy young plasma factors.”

The announcement did not make clear what constitutes “healthy young plasma factors.” However, Josh Mitteldorf over at the Aging Matters blog who has studied the LEF-YBI protocol says

“the blood plasma, clear liquid with all the dissolved signal molecules, will be removed. The plasma will not be replaced by blood plasma from a younger patient, as in a standard plasma transfusion. Instead, the return side will contain only albumin and gamma globulin. “

It’s impractical to wait decades to see if the treatment extends human lifespan, so the investigators plan to use biomarkers of aging as a proxy for the effects of the treatment. The LEF-YBI investigators plan to conduct “extensive baseline measures of aging biomarkers with follow-up tests to assess what degree of regeneration may be occurring.” Faloon did not announce the exact set of biomarkers; however, based on YBI’s website, one assumes it will include a biomarker based on telomere length and another based on the epigenetic clock (DNA methylation age.) As Faloon says

“Leading anti-aging scientists will make use of the Young Blood Institute’s extensive set of aging biomarkers in order to guide individualized consultations throughout this clinical trial.” Adding, “The comprehensive aging biomarker tests alone are very expensive and we plan to repeat them at least 4 times. These types of biomarkers are not normally available to the public, and we estimate the ‘retail’ cost of these tests alone is well over $60,000.”

Here’s the catch – the trial is self-funded by study participants at the cost of $50,000 each, as the LEF announcement says,

“The all-inclusive cost for the initial 5-week clinical trial period that includes 4 sets of aging biomarker tests will be $50,000 per study subject. This sequence of tests is essential if we are to understand what aspects of degenerative aging are being reversed and how future treatment of study participants might best be guided.”

The LEF-YBI experiment is another example of growing trend in patient-funded clinical trials. In this model, the study participant pays nearly all the costs. Being self-funded makes it a lot easier to gather larger amounts of data, as the trial sponsors don’t have to raise funds, a difficult task given the low level of funding available for life extension.

Patient-funded clinical trials are widely criticized because they tend to rule out the ability to select patients at random. Randomization is commonly used in human clinical trials and other experiments to ensure reliable results. Choosing study participants at random guards against selection bias and produces fairly matched comparison groups.

Moreover, patient-funded trials tend to neglect the use of controls. The controls do not receive the treatment and are used for comparison. The control group plays an essential role in well-designed clinical studies and serves as a baseline for ascertaining the effectiveness of the treatment being studied.

Plan A – Alkahest’s Parabiosis Trial

Just last year, Tony Wyss-Coray headed a parabiosis trial along the lines of a plan A through a biotech startup called Alkahest, based in Menlo Park, California. The researchers gave Alzheimer’s patients four doses of young blood plasma. Alkahest’s clinical study was more conventional in that it did not charge participants. The trial was small and aimed to see how well Senior adults can tolerate small doses of plasma.

However, the dose was small as well, a total of 1.5 liters of plasma, and the pro-aging factors weren’t removed from the old blood. The results were disappointing, perhaps because the procedure was not ambitious enough.

Parabiosis Runs in the Blood of these Scientists

Life Extension Advocacy Foundation (LEAF) recently interviewed a pair of experts in the field of parabiosis – Drs. Michael and Irina Conboy from University of California at Berkeley. Dr. Irina Conboy is an Associate Professor in the Department of Bioengineering and an expert in stem cell aging, stem cell niche engineering, and tissue rejuvenation.

In the opinion of Dr. Irina Conboy, plan A – or the transfusion of whole blood or blood plasma – isn’t a viable option and comes with severe side effects. As Dr. Conboy said during the LEAF interview,

“People need to understand not just the titles, abstracts and popular highlights of research papers, but the results and whether they support (or not) the promise of rejuvenation by young blood. In contrast to vampire stories, we have no strong experimental evidence that this is true, and there is a lot of evidence that infusing your body with someone else’s blood has severe side effects (even if it is cell-free).”

Having conducted parabiosis experiments for years, the Conboys noticed that the most significant changes occur in the younger mice in response to the old blood. These rodents became weak like their elderly counterparts. Their results suggest that it may not be factors in the young blood that are rejuvenating, but rather that old blood has pro-aging molecules. While young blood has slight rejuvenating properties, the primary goal of rejuvenation is to remove bad actors from old blood.

Therefore, a more efficient approach would be to figure out which specific factors in old blood are pro-aging and find a way to clear them from the body. This could have profound implications for the treating the chronic diseases of old age, including metabolic changes, frailty, Alzheimer’s, Parkinson’s, and other forms of dementia.

To accomplish this, the Conboys are planning a plasmapheresis process to scrub aged blood and then return it to the patient. As Dr. Conboy told LEAF

“We are working on the NextGen blood apheresis devices to accomplish this.”

History of Parabiosis

The idea of revitalizing aging bodies with new blood has gone on for some time. Back in the 1950s, researcher Clive McCay sewed together the circulatory systems of two mice. Interest in the practice died out, until recently. In 2005 parabiosis became a hot topic once again, when Thomas Rando – director of Stanford University’s Paul F. Glenn Center for the Biology of Aging – performed a modern parabiosis experiment joining the circulatory systems of young and old mice. Rando noticed that the elderly mouse recovered its youthful wound-healing powers, perhaps due to increased stem cell activity. Somehow the older rodent’s stem cells became more effective at growing new tissue. Acting as the repairmen of our bodies, stems cells go into decline as we age.

Since Rando’s discovery, researchers have been analyzing blood samples, searching for compounds that might be responsible for the rejuvenating effects of parabiosis, especially the blood factors that stimulate stem cells. The discovery of such factors could be a boon to tissue regeneration using stem cell therapy.

Eventually, Harvard University biologist Amy Wagers found a protein in the blood called GDF11. Wagers believes the molecule is responsible for faster healing and published the results of her experiments in the journal Science in 2014. The scientist found more GDF11 in younger mice than in older ones. To test out her theory, Wagers injected GDF11 into older mice. The protein appeared to restore muscles to their youthful structure and strength.

Other researchers called her findings into question. For example, a study published in the journal Cell Metabolism suggested that GDF11 increases with age and that some other blood factor is making the cells act younger.

In 2017, Hartmut Geiger, a scientist at the University of Ulm in Germany, announced that a protein called osteopontin might be one of these special blood factors. When Geiger’s team examined the bone marrow of mice, they found that older animals have much lower levels of osteopontin. Geiger suspected that osteopontin in young blood was responsible for keeping blood stem cells healthy, so his team injected stem cells into mice that lacked osteopontin. As a result, the stem cells rapidly because the mice lacked the protein.

Taking the experiment a bit further, Geiger and colleagues mixed older stem cells with osteopontin along with activating protein. Not only did the stem cells thrive, but they also began to produce white blood cells just as young stem cells do. Hartmut Geiger believes that osteopontin makes blood stem cells more youthful. The results are promising, and Geiger is hoping to translate it into a treatment.

Bottom Line

Remember Conboy’s warning on parabiosis that “there is a lot of evidence that infusing your body with someone else’s blood has severe side effects.” It seems that the best approach to obtaining the benefits of young blood is the Conboy’s blood scrubber approach, the implementation of which is far into the future.

Moreover, pay-to-participate trials such as LEF-YBI’s will prove very little if they lack in randomization and proper controls.

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References

Cover photo credit: Wavebreakmedia / Getty Images (iStock).

Guidi, Novella et al. “Osteopontin Attenuates Aging‐associated Phenotypes of Hematopoietic Stem Cells.” The EMBO Journal 36.7 (2017): 840–853. PMC. Web. 22 Jan. 2018. Article link.

Disclaimer

Diagnosis, Treatment, and Advice: This article is intended for educational and informational purposes only and is not a substitute for qualified, professional medical advice. The information and opinions provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. Consult a qualified and licensed physician for the diagnosis and treatment of any and all medical conditions. Experimental treatments such as parabiosis, experimental plasmapheresis or young blood / old blood therapies carry a much higher risk than FDA-approved ones. Call 911, or an equivalent emergency hotline number, for all medical emergencies. As well, consult a licensed, qualified physician before changing your diet, supplement or exercise programs.

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