83 replies to this topic

[Elus]

Young Blood Reverses Signs of Aging in Old Mice: A mysterious substance in blood rejuvenates blood-forming stem cells.

By Emily Singer
Wednesday, January 27, 2010

The antiaging power of blood might not be just the stuff of vampire stories. According to new research from Harvard University, an unspecified factor in the blood of young mice can reverse signs of aging in the circulatory system of older ones. It's not yet clear how these changes affect the animals' overall health or longevity. But the research provides hope that some aspects of aging, such as the age-related decline in the ability to fight infection, might be avoidable.

"At least some age-related defects are reversible, and the factors to reverse them are carried in blood," said Amy Wagers, a researcher at the Harvard Stem Cell Institute and Joslin Diabetes Center, in Boston, at a press conference on Tuesday. Identifying those factors could lead to new strategies to boost resistance to infection, and perhaps a decrease in some cancers, she said.

In the experiment, Wagers and team surgically connected the circulatory systems of two mice, allowing older animals to be exposed to blood--and all the molecules and cells it carries-- from young animals. They found that the procedure made the blood-forming stem cells in older animals act young again; the overall number of these cells decreased, and the cells generated different varieties of blood cells in more appropriate ratios. "In aged animals, many of the changes we see normally that are associated with age were reversed," said Wagers.

The findings, published today in the journal Nature, and which follow similar results with muscle stem cells, also suggest that the regenerative capacity of stem cells is highly influenced by their environment, which could have both positive and negative implications for regenerative medicine.

As we age, our body loses its ability to regenerate different tissues. The circulatory system reflects this decline clearly--the number of blood-forming stem cells, which reside in bone marrow and generate all types of blood cells, increases. But these cells paradoxically lose their ability to repopulate the blood and generate cells in inappropriate ratios, creating too few immune cells, called B lymphocytes, and too many inflammatory cells.

One theory for aging is that our stem cells eventually wear out, thanks to intrinsic changes within the cells. While previous research supports this idea, findings from Wagers and others show that the age-related decline in stem cells is also influenced by external forces. For example, exposing skeletal muscle to blood-borne factors from young mice can restore the regenerative capacity of muscle stem cells.

The regenerative power of young blood appears to be mediated by osteoblasts--bone-forming stem cells previously shown to play a role in regulating blood-forming stem cells. Researchers found that osteoblasts from old animals can make blood-forming stem cells from young mice act old. And conversely, surgically exposing old mice to young blood rejuvenates aged osteoblasts, restoring their capacity to properly regulate blood-forming stem cells.

Researchers haven't yet identified the mysterious molecule in blood that controls these aging effects. But insulin-like growth factor 1 (IGF-1), a hormone that has been shown to regulate longevity in a number of organisms, may play a key role. Researchers found that they could partially correct aging defects in osteoblasts by suppressing IGF-1. On the other hand, suppressing IGF-1 in muscle cells has the opposite effect, highlighting the complex role this molecule probably plays in aging.

It remains to be seen just what effect rejuvenating the circulatory system will have on the animals long-term. For example, scientists haven't assessed whether older mice surgically exposed to young blood are more resistant to infection than their normal aged counterparts. "But there are lots of reasons to link changes in [the circulatory system] with changes in the immune system," said Wagers. Older mice produce fewer lymphocytes, which respond to viruses and other pathogens. And they produce more myeloid cells, which tend to promote inflammatory conditions. "In a lot of tissues, you see an increase in inflammation that occurs with age," said Wagers.

The research also has important implications for regenerative medicine, such as stem cell transplants. "Most effort has focused on how to make [replacement] cells," says Linheng Li, a researcher at the Stowers Institute for Medical Research, in Kansas City, MO, who was not involved the study. "But we need to focus on making cells that function properly." Blood-forming stem cells, for example, are made in great quantities with age. But those cells don't work as well as younger ones. "It highlights the importance of the environment into which you transplant them," said Wagers. "If you take young healthy cells, and put them into an old environment, you might not get the full regenerative benefit of the cells."

Link: http://www.technolog...ne/24421/page2/

Edited by Elus Efelier, 30 January 2010 - 07:51 PM.

[rombus]

I first heard about this a couple of years ago while watching this video of Nadia Rosenthal. I believe she is speaking at Harvard.

This may be of interest to those who have not seen it.

[AgeVivo]

Wagers and team surgically connected the circulatory systems of two mice (...) older animals act young again (...) the regenerative capacity of stem cells is highly influenced by their environment

It is great to see researchers on this track again. A few years/decades ago it was shown that healing properties were also restored (paper by B Carlson I think)

Would it be technically possible to do lifespan tests with surgically connected animals, to see the effect? E.g. Starting with 16 month old mice connected to 4 month old mice? (I wonder if aged mice would live longer than normal but young mice shorter than normal) Starting with 16 month old mice connected to 16 month old mice? (I wonder whether they would live longer). The control would be sham-surgery.

I guess the answer is that it is very complex to do many such surgeries, that mice would die from fighting and tearing their connection, etc. But perhaps not; I've never seen this surgerical connection. Surgical connection might be not only good for a better cellular environnment but also by increasing the robustness of the body: if one organ such as the liver were to have trouble, the organ from the other mouse could compensate. A more human-applicable lifespan test would be regular blood sampling and injections to other mice; there are now simple tools/machines for injection in mice.

[Mind]

This type of effect was also discussed at UABBA, a conference Imminst sponsored 2 years ago. I.M. Conboy review on stem cell signalling pathways, Leanne Jones, age-related changes to the stem cell niche.

So this news was not really anything new to me and the Harvard research did not find the main driving force behind the rejuvenation of the old mice, just more speculation. I suspect it involves several signaling factors working in concert.

[mpe]

This type of effect was also discussed at UABBA, a conference Imminst sponsored 2 years ago. I.M. Conboy review on stem cell signalling pathways, Leanne Jones, age-related changes to the stem cell niche.

So this news was not really anything new to me and the Harvard research did not find the main driving force behind the rejuvenation of the old mice, just more speculation. I suspect it involves several signaling factors working in concert.

I dont think they'll ever find anything in young blood respnsible for the observed regeneration/rejuvenation, because the effect is probably caused by a dilution of the inhibitory factors (eg nf-kb ) in the old animals by the young blood, nothing more.

[JohnD60]

I have heard of this before also. I am surprised there has not been more discussion on of the potential effects this would have upon blood donor criteria. Maybe it would be determined that certain donnees benefited noticably from young blood. What if it was determined that the blood of teens was far superior, would teen blood plasma be brokered at a premium, could teens 'donate' their way through college?

[AgeVivo]

I dont think they'll ever find anything in young blood respnsible for the observed regeneration/rejuvenation, because the effect is probably caused by a dilution of the inhibitory factors (eg nf-kb ) in the old animals by the young blood, nothing more.

Then what do you think of replacing some blood by artificial blood? it would dillute the tgf-beta and other possibly negative signaling factors present in older animals. What do you think of the validity of such an experiment?

[VidX]

IMHO any experiments in that direction are MUST, as this seems to be reappearing here and there for the last few years... We already know that old muscle in mice can be rejuvenated to a young state by a young blood, a whole TISSUE. Isn't that impressive enough??

[mpe]

I dont think they'll ever find anything in young blood respnsible for the observed regeneration/rejuvenation, because the effect is probably caused by a dilution of the inhibitory factors (eg nf-kb ) in the old animals by the young blood, nothing more.

Then what do you think of replacing some blood by artificial blood? it would dillute the tgf-beta and other possibly negative signaling factors present in older animals. What do you think of the validity of such an experiment?

If you could sufficiently dilute the old blood to the same degree as the cojoined mouse experiments, it would be worth doing.

If regeneration then failed to occur it would strongly support the ' Young Bllod Theory '.

I would love to see such an experiment work and the search for a regenerative compound commence.

Sadly I just dont think it will.

[Gerald W. Gaston]

Hmm... completely off the cuff, but this reminds me of something I have wondered about for a few years but never checked into to see if it has been done/thought about until now:

hemodialysis/hemofiltration in middle aged, otherwise healthy mice? Not at the typically three days a week frequency with dialysis for renal failure, but much less frequent. I guess we would have to know what we want to filter out and just how to go about filtering them. A quick look on SD finds this article from 2008 dealing with a proposed 'hemopurifier' that use 'thin fibers to capture and remove viruses from the blood it filters'. :

http://www.scienceda...ected_blood.htm

Will this type of thing be part of our anti-aging future?

[Gerald W. Gaston]

Watching That's Impossible - "Eternal Life" (from 2009) on the History channel tonight... they just went over this mouse experiment. Next up Nanorobots.

[Forever21]

Young Blood Supplement?

Edited by Forever21, 07 February 2010 - 01:24 AM.

[AgeVivo]

what do you think of replacing some blood by artificial blood? it would dillute (...) possibly negative signaling factors present in older animals.

I would love to see such an experiment work (...) Sadly I just dont think it will

Whom should we ask the question? (I mean, which researcher)

[kitinje]

Two possibilities:

1) There are some unknown molecular factors in young blood that contribute in rejuvanating old tissues. (probably something related to satellite cells signaling)
This factors are somehow compromised in aged animals.

2) Inibitory factors are present in aged animals. Dilution of inhibitory factors causes satellite cells to act as "young" again.

Hypothesis 2 could be easier to demonstrate in the short run, while hypothesis 1 would be better for a supplement-like approach.

But even if hypothesis 2 makes more sense to me, I would expect people on daily dialysis to report intensive tissue rejuvenation as a "side effect" of their medical treatment..

[Optimistic]

Two possibilities:

1) There are some unknown molecular factors in young blood that contribute in rejuvanating old tissues. (probably something related to satellite cells signaling)
This factors are somehow compromised in aged animals.

2) Inibitory factors are present in aged animals. Dilution of inhibitory factors causes satellite cells to act as "young" again.

Hypothesis 2 could be easier to demonstrate in the short run, while hypothesis 1 would be better for a supplement-like approach.

But even if hypothesis 2 makes more sense to me, I would expect people on daily dialysis to report intensive tissue rejuvenation as a "side effect" of their medical treatment..

The fact that the young mice in parabiosis with old mice did not suffer any apparent decline in function supports hyp. 1).
If there where inhibitorly factors present in the old mice then parabiosis with a young animal should lead adverse consequences for the function in the young animal.

[VidX]

The fact that the young mice in parabiosis with old mice did not suffer any apparent decline in function supports hyp. 1).
If there where inhibitorly factors present in the old mice then parabiosis with a young animal should lead adverse consequences for the function in the young animal.

Bingo!

[nowayout]

Damn, I wish I knew this sooner. And there I have been using the blood of my virgins for bathing!

Edited by viveutvivas, 20 December 2010 - 10:29 PM.

[Mind]

Another study showing the positive effects of young blood: http://thebunsenburn...ne-in-old-mice/ Slows cognitive decline...in mice.

I posted in a different topic about trying to find all of the growth/signalling factors in young blood in order to create a substance/intervention to rejuvenate older people. I suspect we already have found many of them, just need to get them in the right amounts and test them out. I suspect there are a lot of hormonal components.

[maxwatt]

Suppose you took blood when you are young, froze it, and decades later reinfused it....
It this a possible strategy for young multi-millionaires?

[PWAIN]

Aaaahhhhh: I love my kids.........

[niner]

I have heard of this before also. I am surprised there has not been more discussion on of the potential effects this would have upon blood donor criteria. Maybe it would be determined that certain donnees benefited noticably from young blood. What if it was determined that the blood of teens was far superior, would teen blood plasma be brokered at a premium, could teens 'donate' their way through college?

This could be looked at pretty easily, providing that at least a small amount of donor information (age, at a minimum) remains with the blood. It might turn out that a pint or two isn't enough; maybe you need LOT of young blood, kind of like the Keith Richards transfusion scenario. (The story goes that there was some sort of heroin-kicking scheme involving a complete transfusion, which Richards had done at least once.) Anyway, you'd need to know what the dose-response curve looked like to see if it was going to be feasible or not. I have a feeling that one or two units wouldn't do it.

The factor(s) are presumably in the plasma, and you can donate more plasma than whole blood. If it did turn out to be something that would work without needing an impossible amount of plasma, then maybe there's a business opportunity for ambitious teens. I imagine the medical ethics community would collectively have a cow.

[JohnD60]

Elitist Immortalist Blood Bank feasibility analysis:
Typical adult has 3 liters of blood plasma.
Assuming (big assumption) a twice monthly turnover of blood plasma to maintain youthful blood plasma factor levels, typical adult would need 6 liters of plasma a month.
Blood plasma donation limits vary slightly by weight but on average are 750ml two times a weeks.
6 liters = 8- 750ml donations
Such age restricted blood plasma donation for profit would probably never be permitted in the U.S., and donors would have to be obtained 3rd world.
I think it reasonable to presume that $50 per 750ml donation would be sufficient to guaranty a pool of healthy young 3rd world donors.
Screening, processing, cleaning, transporting, profit, and whatever else they do to blood plasma, would increase the per 750ml donation price to an estimated $800.
8*$800= $6,400/month cost for 6 liters of plasma or $76,800/year
Within the budget of 1% of the U.S. population so approx. 3,000,000 potential clients.
3,000,000 potential clients *$76,800/year = $230 Billion/year potential market

edited because my initial estimate of blood processing cost was evidently very low because it appears a unit of whole blood sells for about $200

Edited by JohnD60, 20 October 2012 - 05:26 PM.

[niner]

Nice analysis! One possible issue, though, is still the legal climate in America. It's illegal to bring in organs from the third world, and I bet the technical wording of the law probably says something like "organs and tissues", which would cover blood, and most likely plasma. Looks like a job for Medical Tourism... Somebody really ought to try this out in humans, and figure out the necessary dose. You know, we certainly used to allow people to sell plasma right here in the US of A. I don't know if we still do or not, but I know people who've done it. Anyway, maybe plasma is in a special category? I actually don't see a big ethical problem with it, as long as the young donors are decently compensated and the procedure is done professionally. The risks they'd be running are pretty low.

[niner]

It occurs to me that sorting out what the factor is might not be that hard. You could chromatograph the plasma on something like a size exclusion column, or silica, or whatever, and collect some number of fractions corresponding to early, middle, and late eluting compounds. If you find the activity in only one fraction, then you chromatographically break it down into smaller fractions, and test them. It wouldn't take very many cycles of this to find the specific compound or compounds. The thing that is really needed is a fast way to assay for activity. If you had to constantly transfuse old mice, it would be a long slog.

[Link]

I wonder if a company could set up a clinic where a "recipient" would go in and pay for a service where by the clinic matches the recipient to a donor and performs the transfer, charging say $1000, then keeping $500 bucks for their service and a $500 cut goes to the donor.

[JohnD60]

As best as I can tell from researching the subject of plasma for dollars, in the U.S., it is not now, nor has it been for a long time, permissible to pay for blood or plasma (a personal pet peeve of mine for a long time). For plasma donation, this rule is side stepped slightly by reimbursing people for the time it takes for them to donate the plasma (I have not donated plasma personally, but understand it takes a few hours for the filtering). It seems to me that current U.S. laws are just insurmountable when considering this on a commercial scale. The only work arounds that I can think of are: 1. move to another country (perhaps living on the Mexican border would be adequate). 2. set up a U.S. 'research clinic' to collect blood (probably a lot of licensing required), pay a premium (the premium would probably have to be paid 'creatively') for 'time', advertise at colleges, screen out everyone over nineteen. 3. Set up a clinic in another country, then import the blood in small amounts under some 'research' exemption (somewaht speculative, I have no idea if such a research exemption exists, but it seems logical). The last work around would work best if the 3rd world clinic was owned and managed by a reputable individual that serviced a modest sized group of elite clients.

Edited by JohnD60, 21 October 2012 - 03:53 PM.

[Ghostdog23]

Hmm, Madonna and her 3rd world adoptions takes a sinister twist.

[Avatar of Horus]

This is a very interesting and relevant topic and research field I think.

I'm currently doing some researching in this subfield, and I intend to write a detailed answers later to the above posts, because IMO there are many important thoughts in them, but for now just some preliminary comments.

(First a side note: it's a sad thing, but since I know about it I have to tell, that
The Nature study referred in initial post was retracted due to scientific misconduct on the part of the main author. See here on the Nature site: /nature/journal/v467/n7317/full/nature09474.html
especially this part:
"specifically the role of osteopontin-positive niche cells in the rejuvenation of haematopoietic stem cells in aged mice"
So only the first part of this study is usable, as another proof of concept for the yound-old thing which is good despite of this.)


Some of the questions expressed earlier in this topic had been answered since by new research,
the one mentioned by Mind in his post above, titled:

The ageing systemic milieu negatively regulates neurogenesis and cognitive function
Nature. 2011 Aug 31;477(7362):90-4. doi: 10.1038/nature10357.
by Dr. Villeda and others.
Available on Pubmed too, its code is: 21886162.

Some of the answers:

about the one that the young recipients are unaffected: it seems that they are not:

"Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age-dependent fashion in mice. Accordingly, exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity, and impaired ... spatial learning and memory."

also they tried to identify the factors with proteomic screening, and they've found some things,
which they also found in humans:
"We identify chemokines--including CCL11 (also known as eotaxin)--the plasma levels of which correlate with reduced neurogenesis in heterochronic parabionts and aged mice, and the levels of which are increased in the plasma and cerebrospinal fluid of healthy ageing humans.
...
CCL11, at the top of this list, is a chemokine involved in allergic responses and not previously linked to aging, neurogenesis, or cognition. Relative levels of CCL11 were increased in plasma of mice during normal aging and within young mice during heterochronic parabiosis Furthermore, we detected an age-related increase in CCL11 in plasma and cerebrospinal fluid; from health human individuals between 20 and 90 years of age, suggesting that this age-related systemic increase is conserved across species."

and they also tested it:

"... increasing peripheral CCL11 chemokine levels in vivo in young mice decreased adult neurogenesis and impaired learning and memory. Together our data indicate that the decline in neurogenesis and cognitive impairments observed during ageing can be in part attributed to changes in blood-borne factors."


This can make some sense in another aspect too, considering that CCL11 is a pro-inflammatory protein and its main 'normal' role is to attract eosinophil granulocytes, usually called eosinophils, a type of white blood cells, which have a function and a role in a number of things, but the relevant one here are that they can produce reactive oxygen species. So with these we arrived to two important things in ageing, the chronic inflammatory state and the ROSs, which is one of the main theories of ageing. So that blood purifier mentioned above also may will have a role.

Furthermore this neurogenesis thing may be of interest to the nootropics people too, so they could be involved also.

I am currently formulating a detailed research project in the Project Ideas thread, in which these and similar things would be researched and tested, so if anyone has any further ideas, please don't hesitate to tell it.

[xEva]

Thank you for posting this. It is very interesting. I'm a bit confused by the following though. Maybe it's my English. The way I understand the quote you give, the young recipients were adversely affected by the old blood; i.e. it impaired their learning and memory -? Are you saying that they are not?

about the one that the young recipients are unaffected: it seems that they are not:

"Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age-dependent fashion in mice. Accordingly, exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity, and impaired ... spatial learning and memory."

[Avatar of Horus]

Thank you for posting this. It is very interesting. I'm a bit confused by the following though. Maybe it's my English. The way I understand the quote you give, the young recipients were adversely affected by the old blood; i.e. it impaired their learning and memory -? Are you saying that they are not?

about the one that the young recipients are unaffected: it seems that they are not:
...

You got it right. I just simplified the sentence.
I meant that: back in the topic, around the 10th-15th posts, there was some speculating whether the old blood has some negative effect on the young pairs, or not.
So my full sentence would be: "that they are not unaffacted"

By the way the free full text of that article is here: http://www.ncbi.nlm....les/PMC3170097/.


It seems that even the old cells and tissues have a good regeneration capacity, just during the ageing process an environment has somehow developed around them, by themselves or another way, that inhibits this ability. Possibly it is some nutrient deficiency or a kind of an 'auto-defensive' systemic mechanism or a mix of these, or something else.

As this regeneration was demonstrated by another researchers too, mentioned here:

It is great to see researchers on this track again. A few years/decades ago it was shown that healing properties were also restored (paper by B Carlson I think)

A paper of this author:
Muscle transplantation between young and old rats: age of host determines recovery.
Carlson BM, Faulkner JA.
Am J Physiol. 1989 Jun;256(6 Pt 1):C1262-6.
pubmed link: http://www.ncbi.nlm..../pubmed/2735398

"Abstract
As compared with age-matched controls, extensor digitorum longus (EDL) muscles autografted in young rats regenerated significantly greater mass (1.8 times) and developed greater maximum contractile force (2.6 times) than EDL muscles autografted in old rats. A cross-age transplantation study showed that the mass and maximum force of old muscles grafted into young hosts were not significantly different from those of young muscles grafted into the same young hosts. Conversely, young muscle grafted into old hosts regenerated no better than old muscles grafted into the same old hosts. We conclude 1) that chronological age alone is not a factor that limits the intrinsic ability of a muscle to regenerate and 2) that the poor regeneration of muscles in old animals is a function of the environment for regeneration provided by the old host."

Edited by Avatar of Horus, 31 March 2013 - 10:28 PM.