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Previously I had searched the CR forums to try to find a discussion of the research into giving older people a transfusion of blood donated by a younger person in order to slow aging. I don't know very much about it, I'm curious about it, and I'm sure that CR folks have been discussing it. But whenever I searched the forum for "blood" or related terms, all kinds of other topics came up and I wasn't able to find it.

 

I wanted to learn more but everything I know about it is from press articles like this one.

 

The other reason I wanted to find a thread about this was that I was going to add a snarky comment that pretty soon ridiculous silicon valley super villains like Peter Thiel were going to start paying the parents of poor children for their young blood. Well I wish I had made that snarky joke, because it's true! Fresh off of his speech endorsing Donald Trump we have this: "Peter Thiel Is Very, Very Interested in Young People's Blood". He really is becoming a cartoon super villain!

 

The research here is genuinely fascinating to me, but I can very easily see a dystopian application where people are essentially coerced by economic circumstances into selling their children's blood to the ultra wealthy who can afford to create an extra-legal parallel health care system to benefit from it. The ethics of this are very troubling and it opens up a number of issues around consent and inequality.
 

 

There are widespread rumors in Silicon Valley, where life-extension science is a popular obsession, that various wealthy individuals from the tech world have already begun practicing parabiosis, spending tens of thousands of dollars for the procedures and young-person-blood, and repeating the exercise several times a year.

 

 

"I suspect we're a little too biased against all these things in society." That's one way of describing ethics I guess.

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Thomas,

 

We talked about parabiosis (aka "young blood therapy") briefly in this thread about GDF11, one protein in young blood that at least was thought to potentially explain the rejuvenating effects of parabiosis. Not surprisingly, it turns out it's more complicated, and likely not a single component of young blood that provides benefits - if benefits are indeed to be had...

 

The research here is genuinely fascinating to me, but I can very easily see a dystopian application where people are essentially coerced by economic circumstances into selling their children's blood to the ultra wealthy who can afford to create an extra-legal parallel health care system to benefit from it. The ethics of this are very troubling and it opens up a number of issues around consent and inequality.

 

I agree it could be a slippery slope, but I must admit I tend to be a bit of libertarian when it comes to practices like this.

 

Healthy blood from a young adult is a valuable, renewable resource. If two consenting adults want to enter into a contract to exchange the healthy young blood of one party for money from the other party, I don't see the harm, and therefore I don't see any ethical problem. I feel the same about paid sperm (or even poop!) donation. No harm, no foul. But I'm less sanguine about selling semi-renewable body components (e.g. eggs, liver) and especially non-renewable bodily parts, like kidneys, corneas or even lungs, which represent a much bigger health risk to the donor, and a much bigger risk of coercive, one-sided transactions imposed on poor people by the rich or simply by desperate life circumstances.

 

Interestingly, in the US you can sell your plasma (but not blood), and in other countries (e.g. Germany, Russia and China) they pay people for blood products. In fact, US blood donors are getting ripped off, since the Red Cross typically charges hospitals between $130-150 for a pint of red blood, and then hospitals mark that up to $200-350 per pint when charging patients or their insurance company. All the donor gets is a silly sticker and a bottle of juice (which most of us wouldn't drink anyway). Not that I'm seriously complaining - I consider it a privilege to help someone in need via blood donation. Heck, I'd feel the same way if my blood would actually help some oldster to live longer.  Sthira speculates here about how our blood might be especially beneficial for recipients. 

 

Almost as bad as the vampires who run academic journals that sell papers to researchers produced by other researchers and reviewed by still other researchers, without compensating any of them...

 

--Dean

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Hi ALL!

 

In the days of the List, Michael Rae posted a note reporting on some research partially funded by SENS (that's Michael's job at SENS) -- the research had been performed at UC Berkeley, and studied several substances that differed in quantity in old and young mice.  One that was relevant was oxytocin -- young mice have more in their blood than old.  The researchers experimented with supplementing old mice with oxytocin -- the result was muscle strengthening.   Oxytocin_muscle_regeneration.pdf

 

The attached file is a copy of the press release from Berkeley, a link to which was supplied in Michael's post.

 

Since then, there also was an article in Science News suggesting that oxytocin supplementation may help strengthen murine bones.

 

In the US, human oxytocin supplementation can be used in research studies, but can not be prescribed for currently unrecognised applications in humans -- in the EU, it can be.

 

  --  Saul

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Young blood antiaging trial raises questions
By Jocelyn Kaiser
Aug. 1, 2016 , 6:15 PM

A controversial pay-to-participate clinical trial will test whether plasma from young donors can counteract aging.
http://www.sciencemag.org/news/2016/08/young-blood-antiaging-trial-raises-questions

Martin Schutt/picture-alliance/dpa/AP Images

It was one of the most mind-bending scientific reports in 2014: Injecting old mice with the plasma portion of blood from young mice seemed to improve the elderly rodents’ memory and ability to learn. Inspired by such findings, a startup company has now launched the first clinical trial in the United States to test the antiaging benefits of young blood in relatively healthy people. But there's a big caveat: It's a pay-to-participate trial, a type that has raised ethical concerns before, most recently in the stem cell field.

The firm’s co-founder and trial principal investigator is a 31-year-old physician named Jesse Karmazin. His company, Ambrosia in Monterey, California, plans to charge participants $8000 for lab tests and a one-time treatment with young plasma. The volunteers don’t have to be sick or even particularly aged—the trial is open to anyone 35 and older. Karmazin notes that the study passed ethical review and argues that it’s not that unusual to charge people to participate in clinical trials.

To some ethicists and researchers, however, the trial raises red flags, both for its cost to participants and for a design that they say is unlikely to deliver much science. “There's just no clinical evidence [that the treatment will be beneficial], and you're basically abusing people's trust and the public excitement around this,” says neuroscientist Tony Wyss-Coray of Stanford University in Palo Alto, California, who led the 2014 young plasma study in mice.

Decades ago, so-called parabiosis studies, in which the circulation of old and young animals was connected so that their blood mingles, suggested that young blood can rejuvenate aging mice. A recent revival of the unusual approach has shown beneficial effects on muscle, the heart, brain, and other organs, and some researchers are scrutinizing young blood for specific factors that explain these observations. The 2014 study, however, suggested that repeated injections of plasma from young animals were an easy alternative to parabiosis. Wyss-Coray has since started a company, Alkahest, that, with Stanford, has launched a study of young plasma in 18 people with Alzheimer’s disease, evaluating its safety and monitoring whether the treatment relieves any cognitive problems or other symptoms. The company covers the participants’ costs. Wyss-Coray expects results by the end of this year. (Another trial at a research hospital in South Korea is examining whether cord blood or plasma can prevent frailty in the elderly.)

In Ambrosia’s trial, 600 people age 35 and older would receive plasma from a donor under age 25, according to the description registered on ClinicalTrials.gov, the federal website intended to track human trials and their results. Karmazin says each person will receive roughly 1.5 liters over 2 days. Before the infusions and 1 month after, their blood will be tested for more than 100 biomarkers that may vary with age, from hemoglobin level to inflammation markers. The $8000 fee—not mentioned on ClinicalTrials.gov—will cover costs such as plasma from a blood bank, lab tests, the ethics review, insurance, and an administrative fee, Karmazin says. “It adds up fairly quickly.”  

Kamarzin became interested in aging as an undergraduate. In medical school at Stanford, where he rotated through labs focused on stem cells and aging, he took note of the young plasma mouse study and other parabiosis research. Karmazin was also intrigued by the story of a Russian physician named Alexander Bogdanov, who in the 1920s gave himself infusions of young human blood that he claimed boosted his energy level and bestowed a more youthful appearance. There are “overwhelming data” suggesting that young plasma will be beneficial to people, Karmazin says.

Last year, Karmazin co-founded a company called xVitality Sciences that aimed to offer plasma treatments at clinics overseas. The venture didn’t pan out—Karmazin left, and the company is now apparently defunct. Karmazin then started Ambrosia with Craig Wright, a former chief scientific officer at a vaccine company, who now runs a clinic in Monterey. The company’s study, which was reviewed by a commercial ethics board used by some for-profit stem cell clinics, doesn’t need approval by the U.S. Food and Drug Administration, the pair says, because plasma transfusions are a well-established, standard treatment. Karmazin says he and Wright have now heard from about 20 prospective participants, and have enrolled three, all elderly. Wright will likely transfuse plasma into the first person in late August.

To bioethicist Leigh Turner at the University of Minnesota, Twin Cities, the study brings to mind a growing number of scientifically dubious trials registered in ClinicalTrials.gov by private, for-profit stem cell clinics. The presence of such trials in the database confers “undeserved legitimacy,” he says.

The scientific design of the trial is drawing concerns as well. “I don’t see how it will be in any way informative or convincing,” says aging biologist Matt Kaeberlein of the University of Washington, Seattle. The participants won’t necessarily be elderly, making it hard to see any effects, and there are no well-accepted biomarkers of aging in blood, he says. “If you’re interested in science,” Wyss-Coray adds, why doesn’t such a large trial include a placebo arm? Karmazin says he can’t expect people to pay knowing they may get a placebo. With physiological measurements taken before and after treatment, each person will serve as their own control, he explains.

Doubts aside, Ambrosia’s trial has already attracted attention from the investment company of billionaire Peter Thiel, who is apparently interested in trying young plasma treatments himself, Inc. reported today. Karmazin says he’s filling a void, suggesting that most companies wouldn’t be interested in developing human plasma as an antiaging treatment. “It’s this extremely abundant therapeutic that's just sitting in blood banks,” he insists.

Edited by AlPater

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So, what does the public think about such things?  It seems to be fairly thumbs down.

 

 

Nature | Seven Days
The week in science: 29 July–4 August 2016
http://www.nature.com/news/the-week-in-science-29-july-4-august-2016-1.20357

TREND WATCH

More than 60% of people in a US survey are concerned about scientific advances being used for human ‘enhancement’, revealed the Pew Research Center in Washington DC on 26 July. The poll asked 4,726 people how they felt about three potential technologies: gene editing to reduce disease risk in babies; brain implants to enhance brain processes; and transfusions of synthetic blood to improve strength. In each case, fewer than half expressed enthusiasm. See go.nature.com/2ag0jjd for more.

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Hi Al!

 

I think that a placebo controlled human study, or a case study, on the effects of Oxytocin supplementation would be a good idea; I'd volunteer.

 

What about youthful plasma injections?  IMO, a very bad idea.  Why?  There are a lot of things in blood that we don't know about.  Many people today are infected with AIDS, and/or hep C, obtained from blood transfusions (given from before these viruses were discovered).  Of course, if you NEED a blood transfusion -- perhaps during critical surgery -- then of course you should take the risk.

 

What about the public's opinion of studies of youthful plasma injection (or of anything else)?  I think that that can be totally ignored.  The opinions of the majority of people is, IMO, irrelevant to the value of any scientific investigation.  (In what you quoted above, the opinion of masses reminds me of Aeosop's fable about "the Fox and the grapes".)

 

:)xyz

 

  --  Saul

 

  -- Saul 

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If the blood/plasma donations can come from consenting adults that makes a big difference to me. Not knowing much about the latest parabiosis research (not even knowing the term parabiosis until this week) I was under the impression that the "young blood" was coming from children in experimental trials.

 

Still I think we should spend a lot more critical energy examining what counts as consent. There are people who "consent" to usurious payday loans with interest rates in excess of 400% but who do so as a last resort because they literally have no other option. To me any genuine sense of consent requires the freedom to do otherwise. If economic circumstances put you in a position where for all practical intents and purposes your only option is to sell blood/plasma for money, I would consider that economic coercion. It's especially troubling since the beneficial and genuinely exciting potential health benefits of parabiosis seem like they might only be available to those who can pony up $8,000 or more. I understand that we are still in a time-frame where we don't understand the benefits and we need to run experiments. Perhaps right now the situation is different and it's not as problematic to charge participants. But my main concern is that if this path does yield health-extending benefits, it will only be available to wealthier people, and that the supply of blood/plasma will be coming from people who could really use an extra $100.

 

I would love to see a system in which 18-year-olds who donate blood/plasma now for someone else could get free transfusions when they are 40 (or whatever the best age to have parabiosis applied).

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Thomas,

 

To me any genuine sense of consent requires the freedom to do otherwise. If economic circumstances put you in a position where for all practical intents and purposes your only option is to sell blood/plasma for money, I would consider that economic coercion. 

 

We're on the same page about this. Financial coercions is a very real concern in this and other circumstances. IMO, we should have a safety net with small enough holes that nobody should be forced to sell their blood or their body parts, or take out a usurious payday loan for that matter, simply to survive. If we had such safeguards in place, I don't see a problem with two consenting adults trading blood products for money. Sometimes it's the rich who have to fund the R&D so that the masses can eventually benefit. It happened with iPhones, and perhaps someday it will happen with longevity treatments.

 

I would love to see a system in which 18-year-olds who donate blood/plasma now for someone else could get free transfusions when they are 40 (or whatever the best age to have parabiosis applied).

 

Neat idea. A parabiosis social security system!

 

--Dean

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I could be wrong about this, but it is my understanding that people who donate one of their kidneys to someone who needs it get to jump to the front of the waiting list in the unlikely event that later on in their life their one remaining kidney fails and they find themselves needing a transplant themselves. That seems like a good policy to me. Something similar for parabiosis would make sense.

 

I'm really looking forward to the day when we can 3d print a kidney. Not their yet, but it seems realistic we will be at some point.

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You may be correct, Thomas.  The thing about donating blood and organs to me is that doing so will lead to greater cell division to replace that which is donated, and greater cell division is one of the mechanisms behind carcinogenesis, it seems to me.  Blood cell cancers are one of the diseases that CR in our furry CRed friends seems protected from.

 

Re kidney donation, the remaining kidney will also grow in size as will other organs, especially livers.  Moreover, live kidney donation, the greatest risk that I perceive is a hugely increased risk that the donor develops end-stage kidney disease.  The average donor of kidneys will get kidney disease and they are carefully screened to have healthy kidneys.  So my brother has stage 4 kidney disease after he lost one to cancer and then got pancreatitis to boot.  His ABO blood type is different from mine, but they have an organ swap program whereby someone willing to donate theirs can swap theirs with another donor who does match and yours matches their intended recipient.  What is one to do?

Edited by AlPater

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Al,

 

You may be correct, Gordo.

 

Gordo? Gordo hasn't participated in this thread. Did you mean Thomas? 

 

[My brother's] ABO blood type is different from mine, but they have an organ swap program whereby someone willing to donate theirs can swap theirs with another donor who does match and yours matches their intended recipient.  What is one to do?

 

Is that a trick question? I guess it depends on how you feel about your brother, but to me it would be a no brainer - sign up for the swap to help my sibling. WIth your healthy lifestyle, you should do just fine with a single kidney, it seems to me. Are you concerned about getting by with just one?

 

--Dean

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Thanks Dean, and I do love my brother.

 

The below paper was what I had in my mind when I said there is a risk from donating a kidney.

 

I specifically had in mind:

 

"Among live donors, with median follow-up of 7.6 years [versus] the unmatched healthy nondonor pool of 9364 ... risk of [end stage renal disease, i.e. dialysis] at 15 years after donation was ... an estimated risk of 22.7 per 10,000 white donors (95% CI, 15.6-30.1) vs 0.0 white nondonors (P < .001)."

 

 

Risk of end-stage renal disease following live kidney donation.
Muzaale AD, Massie AB, Wang MC, Montgomery RA, McBride MA, Wainright JL, Segev DL.
JAMA. 2014 Feb 12;311(6):579-86. doi: 10.1001/jama.2013.285141.
PMID: 24519297
Free PMC Article

Abstract

IMPORTANCE:

Risk of end-stage renal disease (ESRD) in kidney donors has been compared with risk faced by the general population, but the general population represents an unscreened, high-risk comparator. A comparison to similarly screened healthy nondonors would more properly estimate the sequelae of kidney donation.

OBJECTIVES:

To compare the risk of ESRD in kidney donors with that of a healthy cohort of nondonors who are at equally low risk of renal disease and free of contraindications to live donation and to stratify these comparisons by patient demographics.

DESIGN, SETTINGS, AND PARTICIPANTS:

A cohort of 96,217 kidney donors in the United States between April 1994 and November 2011 and a cohort of 20,024 participants of the Third National Health and Nutrition Examination Survey (NHANES III) were linked to Centers for Medicare & Medicaid Services data to ascertain development of ESRD, which was defined as the initiation of maintenance dialysis, placement on the waiting list, or receipt of a living or deceased donor kidney transplant, whichever was identified first. Maximum follow-up was 15.0 years; median follow-up was 7.6 years (interquartile range [iQR], 3.9-11.5 years) for kidney donors and 15.0 years (IQR, 13.7-15.0 years) for matched healthy nondonors.

MAIN OUTCOMES AND MEASURES:

Cumulative incidence and lifetime risk of ESRD.

RESULTS:

Among live donors, with median follow-up of 7.6 years (maximum, 15.0), ESRD developed in 99 individuals in a mean (SD) of 8.6 (3.6) years after donation. Among matched healthy nondonors, with median follow-up of 15.0 years (maximum, 15.0), ESRD developed in 36 nondonors in 10.7 (3.2) years, drawn from 17 ESRD events in the unmatched healthy nondonor pool of 9364. Estimated risk of ESRD at 15 years after donation was 30.8 per 10,000 (95% CI, 24.3-38.5) in kidney donors and 3.9 per 10,000 (95% CI, 0.8-8.9) in their matched healthy nondonor counterparts (P < .001). This difference was observed in both black and white individuals, with an estimated risk of 74.7 per 10,000 black donors (95% CI, 47.8-105.8) vs 23.9 per 10,000 black nondonors (95% CI, 1.6-62.4; P < .001) and an estimated risk of 22.7 per 10,000 white donors (95% CI, 15.6-30.1) vs 0.0 white nondonors (P < .001). Estimated lifetime risk of ESRD was 90 per 10,000 donors, 326 per 10,000 unscreened nondonors (general population), and 14 per 10,000 healthy nondonors.

CONCLUSIONS AND RELEVANCE:

Compared with matched healthy nondonors, kidney donors had an increased risk of ESRD over a median of 7.6 years; however, the magnitude of the absolute risk increase was small. These findings may help inform discussions with persons considering live kidney donation.

Comment in

    Outcomes after living kidney donation: what we still need to know and why. [Am J Kidney Dis. 2014]
    Kidney donation and risk of ESRD. [JAMA. 2014]
    Kidney donation and risk of ESRD. [JAMA. 2014]
    Kidney donation and risk of ESRD--reply. [JAMA. 2014]
    Understanding rare adverse outcomes following living kidney donation. [JAMA. 2014]
    Counseling potential donors to the risk of ESRD after kidney donation: glass half-full or half-empty? [Am J Transplant. 2014]
    Kidney donation and risk of ESRD. [JAMA. 2014]

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A kind off-list correspondent say my message re the public's perception of where science is going with gene editing and such.  I was referred to one account which may have been http://science.sciencemag.org/content/353/6299/545.fulland a second which was http://motherboard.vice.com/read/scientists-argue-the-us-ban-on-human-gene-editing-will-leave-it-behind

Also re such things I now found:

        The Scientist »
        The Nutshell
http://www.the-scientist.com/?articles.view/articleNo/46730/title/NIH-Reveals-Plan-to-Fund-Human-Animal-Chimeras/&utm_campaign=NEWSLETTER_TS_The-Scientist-Daily_2016&utm_source=hs_email&utm_medium=email&utm_content=32546029&_hsenc=p2ANqtz--LNv8xaIhsZHZhn1eelNClLCtcm81SF-1Hvcco-ZeVdpUB3tu1UbUxLmPQzIHYjUoeP0OOa097mP6F8NC6XS0nu5XXRw&_hsmi=32546029

NIH Reveals Plan to Fund Human-Animal Chimeras

The public gets to weigh in before the US government lifts its ban on such research.

By Kerry Grens | August 4, 2016

The US National Institutes of Health (NIH) has outlined a proposal to lift a ban on funding human-animal chimera research—with conditions. “The policy proposes prohibiting the introduction of certain types of human cells into embryos of nonhuman primates, such as monkeys and chimps, at even earlier stages of development than what was currently prohibited,” NPR’s Shots reported today (August 4). Additionally, a committee would review certain experiments that involved, say, human brain tissue.

Last September, NIH placed a moratorium on research that incorporated human pluripotent stem cells into early-stage animal embryos. Earlier rules from the agency don’t allow for human stem cells to contribute to the germ line of animals.

According to a blog post from Carrie Wolinetz, the associate director for science policy at the NIH, a steering committee would decide whether to fund research in two areas: human stem cells incorporated into nonhuman embryos at particular stages of development, and human cells that contribute to animal brain function.

“NIH is seeking public comment on the proposed scope of the chimera research to be considered by the NIH steering committee,” Wolinetz wrote. She added that the agency is also looking to strengthen its ban on breeding animals that have human cells contributing to their brain function and on putting human stem cells into preblastocyst nonhuman primate embryos.

“At the end of the day, we want to make sure this research progresses because it’s very important to our understanding of disease. It’s important to our mission to improve human health,” Wolinetz told NPR. “But we also want to make sure there’s an extra set of eyes on these projects because they do have this ethical set of concerns associated with them.”

Stuart Newman of New York Medical College likened the research to science fiction. “I think that we just can’t say that since it’s possible then let’s do it,” he told NPR.

Members of the public have until September 4 to contribute comments.

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Al,

 

I specifically had in mind:

 
"Among live donors, with median follow-up of 7.6 years [versus] the unmatched healthy nondonor pool of 9364 ... risk of [end stage renal disease, i.e. dialysis] at 15 years after donation was ... an estimated risk of 22.7 per 10,000 white donors (95% CI, 15.6-30.1) vs 0.0 white nondonors (P < .001)."

 

Yes, there is definitely an increased risk of kidney problems if you've only got one of them. But 23/10,000 means your risk would only be 1 in 434. For a stranger that kind of risk would (sadly) be a tough call for me. But it would seem a risk worth taking to save the life of a family member (and someone else) via a multi-person kidney swap. But obviously only you know your circumstances and your brother's well enough to make that call.

 

--Dean

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A kind off-list correspondent suggested a young female's blood might be best for parabiosis.  The below relates to this suggestion.


Letter: Heterosexual parabiosis.
Small FB.
Can Med Assoc J. 1976 May 8;114(9):756-8. No abstract available.
PMID: 773523
Free PMC Article
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1957098/pdf/canmedaj01557-0016.pdf

"a
startling
discovery
of
almost
immediate
practical
value
was
made
when
adult
mice
of
opposite
sex
were
placed
in
parabiosis:
duration
of
para-
biosis
was
reduced
greatly,
only
5
to
10
days
being
required
before
the
animals
could
be
separated
and
successful
skin
grafting
achieved"

A revival of parabiosis in biomedical research.
Eggel A, Wyss-Coray T.
Swiss Med Wkly. 2014 Feb 4;144:w13914. doi: 10.4414/smw.2014.13914. Review.
PMID: 24496774
Free PMC Article
PMID: 24793238
http://www.smw.ch/content/smw-2014-13914/

Abstract

Modern medicine wields the power to treat large numbers of diseases and injuries most of us would have died from just a hundred years ago, yet many of the most devastating diseases of our time are still untreatable. Chronic conditions of age such as cardiovascular disease, diabetes, osteoarthritis or Alzheimer's disease turn out to be of a complexity that may require transformative ideas and paradigms to understand and treat them. Parabiosis, which is characterised by a shared blood supply between two surgically connected animals, may just provide such a transformative experimental paradigm. Although forgotten and shunned now in many countries, it has contributed to major breakthroughs in tumour biology, endocrinology and transplantation research in the past century. Interestingly, recent studies from the United States and Britain are reporting stunning advances in stem cell biology and tissue regeneration using parabiosis between young and old mice, indicating a possible revival of this paradigm. We review here briefly the history of parabiosis and discuss its utility to study physiological and pathophysiological processes. We argue that parabiosis is a technique that should enjoy wider acceptance and application, and that policies should be revisited to allow its use in biomedical research.


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 Jun;20(6):659-63. doi: 10.1038/nm.3569. Epub 2014 May 4.
PMID: 24793238
Free PMC Article
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224436/

Abstract

As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging. Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts--in which circulatory systems of young and aged animals are connected--identified synaptic plasticity-related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function.

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