
Diluting blood plasma rejuvenates tissue, reverses aging in mice - hirundo
https://news.berkeley.edu/2020/06/15/diluting-blood-plasma-rejuvenates-tissue-reverses-aging-in-mice/
======
echelon
Maybe "old blood" has a lot of immune signalling volume going on? Elevated
cytokine/chemokine production, elevated counts of immune cells that recognize
more of the environment than a naive, under-exposed body? Inflammation.

Maybe part of aging is an auto-immune dysfunction?

Granted, this is a very dynamical system. The immune system clears cancers
that are constantly popping up and prevents infections from taking hold.

(This is all unscientific pontificating. I had an undergrad in biochem, but I
don't follow the relevant research.)

Edit: I'm getting downvoted for stating that this is just a theory based on my
undergrad understanding. Does that add too much noise to the conversation? I
wanted to foster discussion. I'm also willing to longbets this one. We're
starting to see the immune system implicated for roles in diseases such as
Alzheimer's, for instance. It's complicated machinery.

Aging has many causes. Oxidative stress is one. Over-stimulation of the immune
system could play a direct role and seems like it's worth exploring, and I'd
bet real money on it.

------
hprotagonist
_Meanwhile, this paper has also just come out, which looks at whether such
effects are due to factors coming in from the young animals or things being
removed from the old ones. The authors, from UC-Berkeley and the California
Pacific Medical Center, are looking at what they call a “neutral blood
exchange”. They replace half the blood volume in mice (both young and old)
with isotonic saline plus added albumin protein. The effect of this on the
older animals was also significant, with noticeable improvements in wound-
healing ability, neurogenesis, and fibrosis /fatty deposits in the liver. The
younger mice were not really changed by the treatment. The authors tried
several control experiments to make sure that this wasn’t an effect being
driven by added albumin protein, and it apparently isn’t. They conclude that
removal and substitution of old plasma “is sufficient for most if not all
observed positive effects on muscle, brain and liver” in parabiosis-type
experiments. It doesn’t exclude the idea of there being beneficial factors in
young plasma, but suggests that this is not the driver of many of the results
seen. (It would be very interesting to check the DNA methylation status of
various tissues before and after this treatment!)

The paper wastes no time in noting that therapeutic plasma exchange (TPE) is
already an FDA-approved process (as witness convalescent plasma treatment in
the current coronavirus epidemic), and it says that Phase II and III human
trials are being planned on the basis of these results. That will be quite
interesting to watch, says the 58-year-old dude writing this blog. Overall, I
still find such results hard to believe, but at the same time they seem to be
showing up from multiple experiments. This second paper especially seems to be
a very testable hypothesis indeed. That’s a good thing, because in the end,
it’s going to be reproducible human clinical data that decide whether this is
real or not – so I’m glad that feasible experiments will allow such data to be
collected. Something to watch. . ._

[https://blogs.sciencemag.org/pipeline/archives/2020/06/12/yo...](https://blogs.sciencemag.org/pipeline/archives/2020/06/12/young-
blood-and-old-blood)

------
macrolime
Interview with the authors about the results:

[https://www.lifespan.io/news/diluting-blood-plasma-
rejuvenat...](https://www.lifespan.io/news/diluting-blood-plasma-rejuvenates-
old-mice/)

An interesting blog post about the same paper:

[https://joshmitteldorf.scienceblog.com/2020/06/08/out-
with-t...](https://joshmitteldorf.scienceblog.com/2020/06/08/out-with-the-old-
blood/)

~~~
James_Henry
Thank you for sharing Josh Mitteldorf's blog on this paper. I think that he
has some useful ideas on how to interpret this in light of Harold Katcher's
work.

------
derefr
Post-hoc "evolutionary just-so story" of the day: animals evolved under
conditions of predation, where they'd tend to lose blood regularly, either in
the process of fighting off/getting away from predators, or in the process of
attacking prey with violent defenses. A species that goes years without losing
_any_ blood, is effectively operating its body in an evolutionary out-of-spec
configuration. It might _work_ , for a while; but it wasn't heavily optimized
for.

A testable hypothesis for this: if you count only the animals that survive
long-enough to die by degenerative disease, then animals that get regularly
bloodied by their predators or prey species should have longer average
lifespans; while animals who don't (e.g. because they have no natural
predators; because they're herbivores; because they prey only upon species
with no violent defenses) should have shorter average lifespans. This
shouldn't be purely a per-species effect, but should also be seen in a
lifespan difference between e.g. wild and zoo animals, if the wild animals
engage in bloody conflict that the zoo animals don't.

Does anyone know if that hypothesis holds up at all? (Maybe/especially if the
question is phrased in terms of heartbeats† rather than years?)

† [http://robdunnlab.com/projects/beats-per-
life/](http://robdunnlab.com/projects/beats-per-life/)

~~~
bloaf
A testable hypothesis for your idea: do women age slower than men.

~~~
spiritplumber
They certainly live longer

------
kgin
The implication is not that young blood has specific positive properties, but
that old blood has specific negative properties. Simply removing some of the
"bad old blood" is already enough to measurably improve biomarkers.
Identifying the bad stuff may go a long way to counteracting it in a more
targeted way.

~~~
naasking
> Simply removing some of the "bad old blood" is already enough to measurably
> improve biomarkers.

God damn it, those blood letters were onto something!

~~~
dundarious
Haha, yes. Probably not a great idea to start blood-letting while fighting an
infection, but as a prophylactic, it looks promising.

------
Udik
There's a Spanish pharma company (Grifols) that has been experimenting for
years with plasma replacement to slow down or stop Alzheimer's disease
progression. The first results of the therapy called AMBAR (Alzheimer's
disease Management by Albumin Replacement) seem to be a slow down of the
progression of the disease by 71% in moderate cases:

"The CDR-Sb scale – which assesses memory, orientation, judgment, community
affairs, home and hobbies, and personal care – showed a 71% reduction in
clinical decline with respect to placebo in patients treated as a whole and in
all three clinical trial treatment arms analyzed separately."

[https://www.webwire.com/ViewPressRel.asp?aId=251270](https://www.webwire.com/ViewPressRel.asp?aId=251270)

Which is interesting because it seems they might have stumbled on a side
effect of something bigger... And it could be possible to check the
participants to the trial for other effects as well.

------
scohesc
Seems like the conspiracy theories that the rich and global elite harvest the
blood of the young and innocent to rejuvenate them isn't as false as we once
thought... /s

Sometimes I wish we had a medical system where whoever wanted to be a test
patient for whatever reason could sign on the dotted line once advised of the
potential downsides (up to and including death assumedly) so we could advance
medical science faster. Maybe we'd find out things a lot faster than we
currently do.

~~~
sp332
Some conspiracy theory, they have a price list.
[https://www.ambrosiaplasma.com/](https://www.ambrosiaplasma.com/)

~~~
M5x7wI3CmbEem10
this is amazing. how did you find this, and do you know of any other
health/longevity tips?

~~~
sp332
Nope, I just heard about it in the news a while back.

------
donclark
What no one has yet discussed is being a plasma donor to keep the bad proteins
down that have accumulated over time. You can donate 1 pint plasma up to twice
a week, they replace it with saline and return the red cells to you. If
someone went weekly, say, they would sooner or later have removed all the old
plasma by dilution with the new plasma that replaces it - I dont have any data
on how many donations it would take to remove 95% of the old plasma. No
albumin is needed since you are only removing 1 unit and the body can replace
it quickly, not like removing half the blood volume at once. Plus, they pay
you to donate. - Jay Caplan

~~~
mdavidn
O- donors have the opposite option: The machine is configured to remove red
cells and return plasma diluted with saline.

------
mcculley
I just gave blood today. I have been trying to give blood as often as possible
(once every eight weeks) to help keep cholesterol and iron low. Now, of
course, I'm getting a free COVID-19 antibody test out of the deal. I'm
wondering if this frequency of blood donations has a similar effect.

~~~
ASalazarMX
> "They replace half the blood volume in mice"

I'd speculate the difference in volume is too great, having half your blood
replaced with saline solution must feel awful.

~~~
aomix
Not really the same thing but I'm blood type O- and do the "Power Red"
donation at Red Cross events. I have two units of blood taken out and the red
cells and plasma are separated so the plasma can be returned along with saline
to make up the difference in volume. I don't notice much of a difference
besides feeling a little cold since the saline is at room temperature. However
in that case I believe I'd only have ~10% of my blood volume replaced with
saline.

~~~
phyzome
« I don't notice much of a difference besides feeling a little cold since the
saline is at room temperature. »

I've always wondered: Why don't they warm it up?!

------
mrfusion
How is this different than donating plasma?

------
wedn3sday
This may go part of the way to explaining why women have a longer life span
then men, they're constantly having to manufacture new blood. Men only have to
create new blood if they donate or suffer some injury, but women's bodies are
generating new blood all the time.

~~~
scottlocklin
There's some research (which I won't dig up at the moment; google "iron
longevity" for a start) indicating that it's actually iron/heme which is bad.
Women can get rid of it, at least while their fertility lasts. Men can't.

~~~
pmiller2
Except that increased female longevity is a trend that carries through many
different mammal species. [0] Not all mammals menstruate in the same manner as
humans. They all have a menstrual _cycle_ , but many have a thin menstrual
lining that's simple reabsorbed by the body rather than being shed in the form
of menses.

\---

[0]: [https://www.smithsonianmag.com/smart-news/females-live-
longe...](https://www.smithsonianmag.com/smart-news/females-live-longer-
malesamong-humans-and-other-mammals-
too-180974504/#:~:text=A%20sweeping%20new%20study%20of,longer%20than%20their%20male%20counterparts&text=Women%20live%20longer%20than%20men,to%20the%20World%20Health%20Organization).

------
RcouF1uZ4gsC
I think popular press of animal studies is mostly clickbait, especially aging
studies.

The lifetimes of mice are so small compared to humans that you have to apply
large scaling factors. An old mouse would be a very young human. How valid the
scaling factors are is a different story.

~~~
James_Henry
In this study they didn't look at the lifespans of the mice, they looked at
markers of the health of different types of tissues. A lot of the time when
something is about "reversing aging" it's about improving health so that
organs of the old work more like those of the young or curing diseases of old
age and not necessarily about increasing lifespan.

------
greggman3
Maybe I should get some pet leeches.

I don't know if Google's search results are accurate but I watched The African
Queen recently and when Bogart gets leeches I googled if they are harmful and
the first results said "No"

~~~
adityapurwa
There are various blood removal method, one of method that I’ve seen and
commonly used is Hijamaz/Bekam. A small incision is made on the skin (usually
the back); then a suction cup is used to draw the blood out. It is widely
popular in Asia, I usually see it done by Moslem as they are recommended by
their prophet to do so. Make sure the method is correct and that the equipment
is sterile though.

~~~
selimthegrim
Is this technically unani tibb

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prmph
So, blood-letting[1] works?

[1] [https://www.history.com/news/a-brief-history-of-
bloodletting](https://www.history.com/news/a-brief-history-of-bloodletting)

~~~
troughway
Lovely anecdote:

A relative of mine has seasonal headaches that they experience, and they have
told me that the way they relieve them is to go and donate blood.

Works every time, without a hitch.

I wouldn't be surprised if there is at least one study out there (or maybe
even a wikipedia page) that attests to this phenomenon.

~~~
James_Henry
The article mentions plasmapheresis, therapeutic plasma exchange, so the
posted article itself attests to this phenomenon.

------
downerending
Scientifically interesting. A lot of people that have acquired the wisdom of
experience would probably shudder at the thought of living 500 years, though.

~~~
etiam
But to no small extent because of people who have not yet acquired the wisdom
of experience. It would be interesting to see the societal effects of a larger
fraction of the population having grown up.

And one could always opt out...

------
carapace
Donate blood, live forever, anti-vampire!

(Sorry, I've been on twitter recently and it's rotting my brain.)

------
demarq
> making conjoined twins out of young and old mice — such that they share
> blood and organs

That sent chills down my spine.

~~~
derefr
Now realize that the young mouse would have to be a clone of the old mouse, to
prevent rejection.

------
ecpottinger
This seems like a simple thing to test. It is just you need some time to see
if it works.

------
mmastrac
Would we see the same effects from donating blood?

~~~
macrolime
Seems there may be some effect at least

[https://sciencenordic.com/body-death-denmark/frequent-
blood-...](https://sciencenordic.com/body-death-denmark/frequent-blood-donors-
live-longer/1425568)

------
thimkerbell
Implications for recruiting plasma donors?

~~~
tropheusduboisi
No plasma donors. Old plasma is replaced with saline and albumin.

~~~
gojomo
In this study, 50% of a body's old plasma is replaced with saline & albumin.

In plasma donation – which can be done in return for cash compensation in the
USA! – 20% of a body's plasma is replaced with saline solution (no albumin).

Plasma donation might plausibly approximate this study's effects, at a lesser
level.

Generally plasma donation is allowed every 28 days, though in some cases 3
donations over 8 weeks (or about once every 12 days) is allowed.

------
M5x7wI3CmbEem10
are there any actions we can take to make use of this new information?

------
exabrial
Basically, stay hydrated? :)

~~~
downerending
This is getting flagged down as a dumb joke, but for those in the cheap seats,
it's not entirely clear exactly how this differs. Presumably adding "adding
albumin and water" is different than just "adding water". But why, exactly?
And so on.

~~~
naasking
It differs because everything except saline and albumin is filtered out. The
point is to show that some markers of aging are harmful byproducts in your
blood, and filtering them out can have positive effects.

~~~
perl4ever
It seems kind of unsurprising to me, given dialysis is a thing.

Actually, now I'm wondering, could this be a simpler substitute for dialysis
in some cases?

~~~
naasking
It's surprising in the sense that even people with fully functioning kidneys
could benefit from it.

~~~
derefr
I would say that it's unsurprising that our organs are less than perfect at
doing their jobs, given that they operate under various constraints (e.g.
running under an ATP power budget, one tuned for an ancestral environment
where dying of hunger was a real concern; being only able to eliminate
metabolic waste at the rate blood flow can take it away; having to avoid
strategies that lead to DNA damage, like running anaerobically for long
periods; etc.)

Therefore, it's also unsurprising that external devices can do some of an
organ's jobs "better" than the organ itself can. They devices don't have the
same constraints our organs do.

This effect is already very clear for pacemakers: hearts are very bad at
keeping _themselves_ going in oxygen-poor conditions (as they effectively have
a circular dependency—a heart can't beat without flowing oxygenated blood);
but electronic pacemakers don't need oxygen, and so keep the heart going under
such conditions, until oxygen-rich blood can return.

Once we perfect stem-cell organ synthesis, it'd be intriguing to know whether
"untethered" human longevity could be increased just by sticking "moar kidney"
and "moar liver" into the body, than the human body-plan calls for by default.

------
el_nahual
Reminds me of the joke:

What do you tell a mouse that has cancer or diabetes?

"You need a new agent!"

