Evidence to Suggest Parabiosis Effects Result from Dilution of Damage

Heterochronic parabiosis involves joining the circulatory systems of an old and a young mouse. This produces harmful effects on the young mouse and beneficial effects on the old mouse. There is considerable interest in the research community in identifying the molecular signals involved. So far theory has focused on delivery of beneficial signals from young blood to the old individual, but here researchers present evidence to suggest it may be more a matter of diluting detrimental signals present in the old blood. This has implications for efforts to build therapies based on transfusions of young blood: if dilution is the primary mechanism, those efforts will have little to no effect.

A new study found that tissue health and repair dramatically decline in young mice when half of their blood is replaced with blood from old mice. The study argues against the rejuvenating properties of young blood and points to old blood, or molecules within, as driving the aging process. "Our study suggests that young blood by itself will not work as effective medicine. It's more accurate to say that there are inhibitors in old blood that we need to target to reverse aging." In 2005, researchers found evidence for tissue rejuvenation in older mice when they are surgically joined to younger mice so that blood is exchanged between the two. Despite remaining questions about the mechanism underlying this rejuvenation, media coverage of the study fixated on the potential of young blood to reverse the aging process, and on comparisons to vampires, which was not the takeaway from the study. In the years since the 2005 study, scientists have spent millions to investigate the potential medical properties of youthful blood with enterprises emerging to infuse old people with young blood. "What we showed in 2005 was evidence that aging is reversible and is not set in stone. Under no circumstances were we saying that infusions of young blood into elderly is medicine."

While the experimental model used in the 2005 study found evidence that some aspects of aging may be reversed, the techniques used in the study do not allow scientists to precisely control the exchange of blood, which is necessary to dig deeper into blood's effect on aging. When two mice are sutured together, a technique called parabiosis, blood is not the only thing that is exchanged in this setup; organs are also shared, so old mice get access to younger lungs, thymus-immune system, heart, liver and kidneys. In surgical suturing it takes weeks to a month for the effects of blood to take place and the precise timing is not actually known. Nor is the precise amount of the exchanged blood. In the new study, researchers developed an experimental technique to exchange blood between mice without joining them so that scientists can control blood circulation and conduct precise measurements on how old mice respond to young blood, and vice versa. In the new system, mice are connected and disconnected at will, removing the influence of shared organs or of any adaptation to being joined. One of the more surprising discoveries of this study was the very quick onset of the effects of blood on the health and repair of multiple tissues, including muscle, liver and brain. The effects were seen around 24 hours after exchange.

With the new experimental setup, the research team repeated the experiments from 2005. In each test, blood was exchanged between an old mouse and a young mouse until each mouse had half its blood from the other. The researchers then tested various indicators of aging in each mouse, such as liver cell growth as well as liver fibrosis and adiposity (fat), brain cell development in the region that is needed for learning and memory, muscle strength and muscle tissue repair. In many of these experiments, older mice that received younger blood saw either slight or no significant improvements compared to old mice with old blood. Young mice that received older blood, however, saw large declines in most of these tissues or organs. The most telling data was found when researchers tested blood's impact on new neuron production in the area of the brain where memory and learning are formed. In these experiments, older mice showed no significant improvement in brain neuron stem cells after receiving younger blood, but younger mice that received older blood saw a more than twofold drop in brain cell development compared to normal young mice. The researchers think that many benefits seen in old mice after receiving young blood might be due to the young blood diluting the concentration of inhibitors in the old blood.

Link: http://news.berkeley.edu/2016/11/22/young-blood-does-not-reverse-aging-in-old-mice-uc-berkeley-study-finds/


I wonder if donating blood has any longevity benefit. Starting this year I've been giving every two months, if it turns out it doesn't at least I've helped other people.

Posted by: Corbin at November 23rd, 2016 10:09 AM

Irina has been very rational about this since the start. While some people were creating companies she was carrying on with the research.
Even in 2014 when the parabiosis hype was still strong there were scientists saying - it ain't so.

Meanwhile Alkahest maybe were a bit too early to open the champagne bottles.

Either way. The trials are on the way, this saga will end in an year or two and geroscience will be able to move forward.

Posted by: Anonymoose at November 23rd, 2016 11:20 AM

Diluting out junk like atrial natriuretic peptide and transthyretin—not just bad signaling—might be the mechanism behind the beneficial effects of parabiosis. It's kind of ironic that what would have amounted to bloodletting in past centuries might become an effective SENS therapy.

Posted by: Florin Clapa at November 23rd, 2016 6:14 PM

I am surprised people are not seeing the importance of this research. It is much easier to filter plasma of bad metabolites than it is to create metabolites de novo and administer them. If young blood contained metabolites that made old people young, the economics of making that cheaply and the FDA approvals alone would bury the discovery from practical application in humans for 20 years.

On the other hand, if the old blood simply contains extra metabolites that need filtering, that can be done by existing and approved technology with probably very simple tweaking. This is something that could start being used on a wide scale in humans within 10 years if their plasmapheresis experiments bear out their thesis.

This is an incredibly important study and people need to bookmark it and discuss it.

Posted by: P One at March 28th, 2017 3:14 AM
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