Posted on 12 April 2021
What if we told you that a procedure shown to reverse ageing in mice is currently being performed routinely in humans in hospitals around the world? It seems too good to be true, but there is evidence that blood transfusion from a younger to an older individual can slow or even reverse some aspects of the ageing process.
Evidence of the link between the blood and ageing is as old as the 1950s, but the study that really kicked off the field was published in 2005. Irina Conboy and colleagues connected the circulatory systems of a young mouse and an old mouse using a technique called parabiosis, and found that the procedure reversed signs of ageing in muscle and liver tissue in the older mice. Further experiments have found a growing number of aged organs and tissues that benefit from exposure to young blood, including the brain, heart, bone, kidneys, pancreas, and aorta. It was also discovered that mice don’t need to be joined together to see these effects: it is sufficient to extract blood from a young mouse and infuse it into the circulation of the older mouse repeatedly.
What could be the basis of this effect? The circulatory system is the organ system that links all tissues of the body together. Factors produced by any tissue can enter the blood, and factors within the blood can affect any and all tissues, making the blood a ‘communications highway’ between every organ in the body. Perhaps it is not so surprising that the ageing of our organs correlates with measurable changes in factors within the blood. Research suggests that these factors rise and fall in ‘waves of ageing’ throughout life. But how does transferring blood containing ‘young factors’ rejuvenate older tissues? There are two schools of thought to explain why this occurs, though they are not mutually exclusive.
Perhaps the most straightforward explanation for the rejuvenating properties of young blood is that there must be factors, present in the blood of young but not old individuals, that have rejuvenating effects on cells and tissues. This would mean that if we could identify those specific molecules in humans, we could isolate and administer them as an anti-ageing treatment. This is no small task, however. There are countless molecules present within the blood, many of them in extremely small quantities. However, progress has been made.
Studies over the years have been able to reproduce some of the effects of young blood transfer in mice using specific factors. Some companies are confident enough about the benefits of these factors that they have begun to conduct clinical trials in humans, with the aim of treating age-related diseases like Alzheimer’s using plasma fractions. Last year, a preprint study was published in which researchers developed a cocktail of blood factors that reduced epigenetic age (a measure of true biological age) by 54% across 4 tissues in rats. All in all, a fairly compelling argument can be made, based on the research so far, that there are factors in young blood with rejuvenating properties.
You may be wondering: if young blood can rejuvenate old mice, does old blood also make young mice age faster? The answer appears to be yes: studies have identified factors in old blood that can promote ageing in young tissues. This is not particularly surprising if we view blood factors as important regulators of ageing. What is surprising is that simply diluting these factors has the potential to rejuvenate aged tissues.
In 2016, Irina Conboy’s group (the same that made the original parabiosis findings in 2005) made a surprising discovery. By simply injecting mice with a mixture of saline solution and albumin, they were able to achieve significant rejuvenating effects on the body and the brain. This begs the question: were young blood factors really responsible for the rejuvenation seen in the first parabiosis experiments? Or did the sharing of blood simply dilute the older animal’s old blood factors, and allow them to be filtered by the younger animals more efficient kidneys and liver?
As already mentioned, these theories are not mutually exclusive, and given the evidence, it seems likely that both ‘youth factors’ and ‘ageing factors’ have a role to play. However, it is beginning to look as though ‘ageing factors’ may play the more important role. Why?
Firstly, many specific factors that are more abundant in blood from aged organisms have been shown to be solely capable of promoting ageing. Comparatively, the evidence for factors that can cause rejuvenation is less robust, though that is not to say that they don’t exist.
Secondly, when blood from a young animal is used to replace some of the blood of the older animal, the effects are less impressive than what is seen in parabiosis, in which the old animal’s blood is also being filtered by the younger animal’s organs. The effects of ‘old blood’ on younger animals, however, seems unchanged. This suggests that at least some of the effects of parabiosis are the result of the removal of harmful substances by the younger animal’s kidneys and liver.
Finally, as discussed above, the simple dilution of the blood produces strong rejuvenating effects in old animals – no young factors needed. In fact, in the case of neurogenesis (the growth of new neurons) dilution actually produced greater rejuvenating effects than parabiosis. On the flip side, diluting the blood of young animals did not make them age any faster. If youthfulness is maintained by factors circulating in the blood, we might have expected to see more rapid ageing when said factors are diluted.
The take home message is that while different factors within the blood rise and fall throughout life, recent research is pointing to factors that increase with age as being more important to the link between blood and the ageing process. Unfortunately, when considering the prospect of treating ageing in humans, introducing new factors into the blood is more straightforward than removing harmful ones. With this being said, clinical trials have produced promising results for the use of plasma factors in the treatment of age-related diseases, and ‘young blood’ factors may yet prove to be effective in humans.
List of clinical trials conducted by Alkahest
Young Donor Plasma Transfusion and Age-Related Biomarkers: NCT02803554
Plasma Transfusions for Progressive Supranuclear Palsy: NCT02460731
Plasma From Young Donors for Treatment of Moderate Parkinson’s Disease: NCT02968433
Reversing Epigenetic & Other Markers of Senescence by Transfusing Young Plasma: NCT03353597
Safety and Efficacy of GMFFP From Young Healthy Donors: NCT03458429
Human Umbilical Cord Blood Plasma Infusion for Age-Related Cognitive Decline: NCT04566757
Parabiosis: the Dilution Solution?: https://www.sens.org/parabiosis-the-dilution-solution/
Undulating changes in human plasma proteome profiles across the lifespan: https://doi.org/10.1038/s41591-019-0673-2
Rejuvenation of aged progenitor cells by exposure to a young systemic environment: https://doi.org/10.1038/nature03260
Reversing age: dual species measurement of epigenetic age with a single clock: https://doi.org/10.1101/2020.05.07.082917
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