Young Blood: Heterochronic Parabiosis Rejuvenated Adult Stem Cells Across Mouse Tissues

On this week’s episode: Researchers at the Chinese Academy of Sciences found that heterochronic #parabiosis rejuvenated adult stem cells across mouse tissues.

@CellStemCell

Heterochronic parabiosis induces stem cell revitalization and systemic rejuvenation across aged tissues

paper: https://bit.ly/3NcgYrh
Listen to the discussion: https://bit.ly/3N7gkvj

An interesting new study. Given all the background of research on young blood / heterochronic parabiosis it seems likely that large and regular transfusions of young blood into older bodies will ultimately be proven to have a significant positive impact on lifespan.

Heterochronic Parabiosis is one approach for research, but it seems that given the influx of “old blood” into the young mouse and the problems that would cause, the better approach for translation to a clinical application would be a continual or pulsed supply of young blood from numerous young mice. Of course, in humans this would be very expensive and problematic at an image/social level. I know that the Cowboys at UC Berkeley, and others, are looking to isolate and productize all the blood factors that are responsible for these effects but this is something that could (relatively easily) be done today simply with young blood. And of course, the next level up would be to get the young blood from high-performing young athletes… as was done in this study (in mice).

I discussed this with Irina Conboy in another forum, and she really wants to steer people away from the young blood transfusion area (primarily, I think, due to the negative optics of older people taking blood from younger people). But, if money is no object, its probably available. (though Jesse Karmazin’s startups - Ambrosia and Ivy, seem to have been shuttered).

young blood background reading

Multi-omic Rejuvenation and Lifespan Extension upon Exposure to youthful Blood Circulation

This is fascinating stuff, not related at all with mTOR I don’t think.

Similarly (more?) fascinating, the Conboy lab simply replaced by old blood
plasma with saline-albumin! Namely, simply “diluting the plasma factors”.

“A model of action (supported by a large body of published data) is that significant dilution of autoregulatory proteins that crosstalk to multiple signaling pathways (with their own feedback loops) would, through changes in gene expression, have long-lasting molecular and functional effects that are consistent with our observations”

So CR with time restricted feeding, Rapamycin, and replacing blood with saline/albumin…150 yrs?

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Yes - there is a doctor in San Francisco (who is working with the Conboys) offering Blood Plasma exchange already as a service.

It seems that reducing the negative blood factors in older people is one positive approach, and then another level is removing, and replacing the old blood factors with young, (and ideally athletic), blood factors is probably even better.

Lou Hawthorne documented his experience with it here:

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Watch out young people, the New World Order will come for you.
(Only partially kidding.)

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One of the posted article’s
$8,000 for one liter.

How many people would have the resource$?

$32,000 a year for one liter dose per quarter.

Actually - in an ideal world I suspect that what you’d want to do is probably do a full transfusion (say 5 liters of blood) and probably do it more frequently then every quarter - so lets say every month…

$8K X 5 liters = $40K per month
12 months = $480,000 per year

Nothing the Saudi Royal Family would have a problem with :wink: when they are already spending $1.5 million for a health checkup:

Harold Karcher has supposedly come up with an elegant simple “elixir” that promises rejuvenation that does away with the need for plasma exchanging/dilution.

Yes - Harold Katcher’s company is one of the groups doing work in this area… the Conboys have a company also, and others out of Stanford, etc. Lots of money going into the “blood factors” area. Someone, eventually will do well in this area I suspect.

Blows me away how many longevity pathways in play.

Shows how immensely complex is the human organism. Is there a universal master key to all of these?

This debate has been raging for some time now.
Is it preferable to remove the old bad stuff and just replace it with a neutral solution like saline/ albumin ( though it can be argued that albumin has longevity properties of its own and isn’t neutral) as in the Conboy’s thinking, or should we try to identify the good stuff in young blood and just infuse it as in Harold’s thinking.
Harold did get a good epigenetic response from his elixir, but according to Josh Mitteldorf, the longevity trial isn’t going as well as anticipated .

I think that there’s something legit in all of this but it will still take some time to work through it.

@rivasp12

Question: when we donate blood, the body needs to replace what we dumped. Are we producing “new/younger” versions, or replicating the old? Are we engaging our young stem cells? At a minimum we are dumping some old glycated and misfolded junk?

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When you donate blood your kidneys sense a drop in oxygen and release erythropoietin which then signals the stem cells in your marrow to produce nice new and young RBC’s.
After 120 days their membranes exhibit signs of wear and tear and are eliminated by your liver and spleen mostly.

Nice and new RBC’s other than maybe epigenetic (not unimportant) are not impacting cellular dynamics?

What about the proteome rebuild?

White blood cells?

Yes WBC’s also go down in up to 50 % of donors and these too are replaced.
The proteome differs across different cell types and is dynamic and responsive to the environment so it’s in constant flux.

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Whether young blood factors or diluting old proteome, can I pin you down that it’s something in the proteome?

Or possibly (only) also white blood cell factors? Sorry, hedging :upside_down_face:

Proof in a mouse model, that replacing damaged albumin with new albumin EXTENDS lifespan.

From an exchange with the author, she confirmed that donating blood does indeed result in NEW albumin creation (my archive)

Young and Undamaged rMSA Improves the Healthspan and Lifespan of Mice (2021)

The healthspan and lifespan of C57BL/6N mice were significantly improved by rMSA (recombinant mouse serum albumin). The rMSA used in this study is young and almost undamaged. We define the concept “young and undamaged” to any protein without any unnecessary modifications by four parameters: intact free thiol (if any), no carbonylation, no advanced glycation end-product, and no homocysteinylation. Undamaged proteins altogether can further improve the healthspan and lifespan of mice

Human serum albumin is the most abundant protein in blood plasma with a serum half-life of about 21 days. Damages or unnecessary modifications of HSA are related to many pathological conditions and increase with age. Firstly, the single free thiol in Cys-34 residue of HSA has been proposed to account for approximately 80% of the total free thiols in plasma, whose oxidation is intimately linked with aging and age-related diseases. Secondly, in oxidative environments, carbonyls are also formed especially on the side chains of Pro, Arg, Lys and Thr residues in proteins. Elevated carbonyl levels in HSA have been found to be related to aging and varieties of diseases. Thirdly, the AGE accumulation of HSA is another important factor found to be involved in aging. It is widely reported that AGE formation impairs normal functions of albumin and can induce inflammatory responses, which is connected with aging and the progression of serious diseases. Fourthly, it has been widely reported that homocysteine (Hcy) increases with age and is associated with agerelated degenerative disorders. HSA is a major target for homocysteinylation, thus it can efficiently protect other proteins from the toxicity of Hcy.

In 2014, Wyss-Coray group reported that plasma from young mice can improve the learning and memory of old mice. Since albumin occupies about 50% of total plasma proteins, it most likely plays the most important role in this process, which was exactly what we found here. In order to achieve the maximal effect of rMSA on longevity, a variety of measures including optimal dosage, frequency, and drug delivery methods are being investigated. We predict that the concept of young and undamaged albumin increasing the longevity can also be applied to any other proteins such as immunoglobulins, fibrinogen, transferrin, transthyretin, and haptoglobin which are major plasma proteins. If so, the combination of young and undamaged major plasma proteins can further increase the longevity. Ideally, all of the young and undamaged plasma proteins altogether can increase he longevity to the largest extent.

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So this is very interesting. The Conboy’s replacement of old blood with saline/ albumin makes you now wonder what exactly caused the benefits. Was it mainly the albumin?
I wonder if blood donations increase multiple new proteins and not just albumin. Would this be reflected in increased blood levels? Have you noticed an increase in albumin after donating?

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Yes, I’d concur with you…new albumins, not dilution.

Secondly, why wouldn’t donation create a full new generation of the proteome? After zillions of blood donations, surely there’d be findings of metabolic dysfunction if only certain elements of the proteome?

“Increase in albumin”? Isn’t this about the quality of the albumin vs qty? But no, I’ve only tested albumin 3x in 5 yrs, no trending.

I see what you’re saying. The old albumin replaced by the new giving higher quality, not quantity.
Makes you now really wonder if frequent/ regular blood donations should be an integral part of the health/ longevity regimen for a whole multitude of reasons.

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Yes, I am tending towards that conclusion.

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