Systemic induction of senescence in young mice after single heterochronic blood exchange

Ageing is the largest risk factor for many chronic diseases. Studies of heterochronic parabiosis, substantiated by blood exchange and old plasma dilution, show that old-age-related factors are systemically propagated and have pro-geronic effects in young mice. However, the underlying mechanisms how bloodborne factors promote ageing remain largely unknown. Here, using heterochronic blood exchange in male mice, we show that aged mouse blood induces cell and tissue senescence in young animals after one single exchange. This induction of senescence is abrogated if old animals are treated with senolytic drugs before blood exchange, therefore attenuating the pro-geronic influence of old blood on young mice. Hence, cellular senescence is neither simply a response to stress and damage that increases with age, nor a chronological cell-intrinsic phenomenon. Instead, senescence quickly and robustly spreads to young mice from old blood. Clearing senescence cells that accumulate with age rejuvenates old circulating blood and improves the health of multiple tissues.

https://www.nature.com/articles/s42255-022-00609-6

It’s looking more and more like vampires have it right😆

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This is such a fascinating debate. Harold Kutcher believes that young blood contains youthening signals that attenuate over time , thus causing aging. Replace those signals and aging may stop, or even reverse.
The Conboy’s are at the opposite end of the spectrum. They think that old blood sends out aging signals that directly cause aging itself.
There are studies that support both positions.

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Correction. Katcher.

Hop on the blood dumping train, even if it’s a small signal, I believe it was far ranging rejuvenating and chronic disease preventative efficacy (covered in other posts).

“Here, using heterochronic blood exchange in male mice, we show that aged mouse blood induces cell and tissue senescence in young animals after one single exchange. This induction of senescence is abrogated if old animals are treated with senolytic drugs before blood exchange, therefore attenuating the pro-geronic influence of old blood on young mice. Hence, cellular senescence is neither simply a response to stress and damage that increases with age, nor a chronological cell-intrinsic phenomenon. Instead, senescence quickly and robustly spreads to young mice from old blood. Clearing senescence cells that accumulate with age rejuvenates old circulating blood and improves the health of multiple tissues.”

This is such a profound few sentences, haven’t found full access yet.

Dynamic senescence…one exchange can radically alter phenotype?

Katcher is injecting a younger proteome. In this Conboy paper, it’s classic heterochronic blood exchange, which is also diluting the old proteome. Conboys have also shown that diluting old proteome also results in rejuvenating type milieu.

I hope Katcher’s work truly shows merit…I’d much rather take a few shots at some efficacious rejuvenating dose/frequency of youthing agents vs physically diluting my blood or doing TPE at some longer interval.

Is this all really the same principle…DILUTING the signal of old proteome??

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It’s also possible that neither of these approaches will work over the long term and are only giving transitory effects. Actual aging reversal may have to begin at the cellular level.

Quite possibly yes…so maybe a DAILY shot of Katcher’s brew! Dose is the poison and possibly…the cure. I’ll stay optimistic.

Here’s the paper, I emailed copy request to Irina Conboy.

https://www.nature.com/articles/s42255-022-00609-6.epdf?sharing_token=UYmJFfOkCCEVzGI50HP3WtRgN0jAjWel9jnR3ZoTv0MM4Ysh4mn4RLp4AGGAgbbGs8jhEffmu_2GzTblOVqLqQZOdB8UA77wXKsZFukXiHFRwnxFHOvf5DAl-AShVELGa7g4LuivNIky29A7eHx9Vm5KD9yTyzDv1VBF8TGg_tg%3D

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A brief Q&A email exchange with Irina Conboy:

MAC:

You write “mammalian aging related to excess of systemic factors”
Is this work consistent with your previous albumin dilution work and could similar “attenuation” be also the mechanism of the supposed rat rejuvenating experiments of Harold Katcher?
Are these modalities all fundamentally rejuvenation inter related…diluting old signalling molecules?

IRINA:

This paper confirms that neither aging nor rejuvenation are driven by “young blood” and instead, it is the excess of age-elevated circulating factors that causes aging, while their removal leads to health enhancements.

Harold thinks that he knows the young blood factor that can be added to old rats to make them younger, so he is “on the wagon” of the young blood as the medicine. Was his manuscript published and is there convincing experimental data?

MAC:

If you are right, diluting old systemic factors.
How do you then theorize we are going to translate to human intervention?
TPE?*

*Understanding Therapeutic Plasma Exchange (TPE) | Saint Luke's Health System

She hasn’t responded to my last question. Also note the use of senolytics in this paper.

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No response back yet from the clinical trial people (they send out a detailed questionnaire, but since then, nothing - maybe I didn’t make the cut): Plasmapheresis Startup Looking for Clinical Trial Participants SF Bay Area

Last year the Conboys were talking about their company focused on the rejuvenating factors to add to the blood, but its been silent since then. I wonder if they’ve given up on it. She seems much more on the “removal of old systemic factors” now.

Regarding the paper:

Dunno, haven’t followed Conboy machinations too closely lately, but perhaps so. I sure hope we can just “add” something re human translation rather than having to dump my blood. The paper also shows that a “senolytic” treatment can abrogate aged factors…perhaps another alternative pathway to reducing aging factors??

Above article focuses mainly on young vs old cerebrospinal fluid but seems relevant.

Will be interesting to know how much of the “bad actors” in old blood is from whole senescent cells that may be amenable to senolytic treatment vs proteins, etc that would presumably need to be filtered out.

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"This paper confirms that neither aging nor rejuvenation are driven by “young blood”

Thank God I won’t have to go night stalking!

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And I’ll cancel the order for the blood boy :wink:

So those dark ages physicians had it right. Blood letting and leeches. :grimacing:

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“Transfusion associate”…LOL

Seriously, I think there’s a business model here…

YouBER or YouthingRus or Ferrocity

The “transferring” economy…build an algo to properly match people, outsource to a clinical setting, charge for labs and monitoring for recurring revenue. Upsell the post donation salty crackers. Post donation trauma psychologists, on and on…

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If Conboy is right, I’m imagining a machine similar to dialysis where you hook up to it (hopefully MUCH less frequently than 3x weekly!!:laughing:) and it selectively filters out the toxic age-promoting cells/proteins while you sit and watch TV/phone/laptop/etc, perhaps by filtering through some kind of membrane that contains fixed antibodies which selectively and irreversibly latch onto epitopes on the toxic cells/proteins. This would completely obviate the need for “young donors” and whatnot.

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At several thou$and$ per treatment. Out of pocket.

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Shouldn’t there be a chemical or substance that can bond to the toxins so that you can excrete them? This is the thought behind NAC (and glutathione) which detoxifies the body by bonding to heavy metals so that you can excrete them. Seems better than blood filtering. Any other substances besides NAC that does this?

It’s more complicated than that.[quote=“DeStrider, post:18, topic:2444, full:true”]
Shouldn’t there be a chemical or substance that can bond to the toxins so that you can excrete them? This is the thought behind NAC (and glutathione) which detoxifies the body by bonding to heavy metals so that you can excrete them. Seems better than blood filtering. Any other substances besides NAC that does this?
[/quote]

It’s more complicated than that.

I have a feeling Conboy et al are waaaaay ahead of me here and are already planning something like this.