Does old blood induce senescence?
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- Опубліковано 12 сер 2022
- A landmark study that came out in 2005 showed that if you fused the blood systems of old and young mice, a process known as heterochronic parabiosis, it rejuvenated the cells of old mice. It suggested that there was something in the blood and there were two possible explanations; there were rejuvenating factors in the young blood, or there was dilution of pro-aging factors in the old blood. Or some combination of both.
Well, since 2005 more studies have come out. A 2016 study showed that heterochronic blood exchange, so just transfer from young to old, or old to young, without fusing, had a greater impact when old blood was given to young, than when young blood was given to old. In better words, “the inhibitory effects of old blood are more pronounced than the benefits of young”.
So, somewhat ruling out “factors in the young blood”. But even more support came from studies published a few years ago, where again they supported this latter theory. You see, simply diluting the old blood, that is taking plasma out of blood of the old mice and replacing it with saline and albumin (abundant protein found in blood) had the same effect. This process, known as neutral plasma exchange, involves no Frankenstein surgery or young blood vampire like scenario. AMAZING.
But, it still didn’t address why or how? The authors of that paper left us with this rather interesting hypothetical hypothesis graph of what potentially might be happening to some factors present in the blood, but they were otherwise unsure on what or how these beneficial effects were being achieved. What were the important factors to remove?
Well, we now have more answers. But first we need to introduce cellular senescence.
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References:
Jeon, O.H., Mehdipour, M., Gil, TH. et al. Systemic induction of senescence in young mice after single heterochronic blood exchange. Nat Metab (2022). doi.org/10.1038/s42255-022-00...
Conboy, I., Conboy, M., Wagers, A. et al. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433, 760-764 (2005). doi.org/10.1038/nature03260
Xu, M., Pirtskhalava, T., Farr, J.N. et al. Senolytics improve physical function and increase lifespan in old age. Nat Med 24, 1246-1256 (2018). doi.org/10.1038/s41591-018-00...
Senescence in Health and Disease - dx.doi.org/10.1016/j.cell.2017...
Please note that The Sheekey Science Show is distinct from Eleanor Sheekey's teaching and research roles at the University of Cambridge. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Sheekey Science Show and guests assume no liability for the application of the information discussed.
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So interesting.
Love this!
I'm not a specialist, but maybe it would be worth comparing the blood of long-lived animals like turtles or naked mole-rat and test their blood for substances that are not found in short-lived animals.
Hidden gem channel! 💎
Thank you! This is an important research area. As a regular blood and platelet donor I added monthly plasma donation to my regime at beginning of 2022 after doing it a few times last year. It's free and doesn't require a specific medical reason like therapeutic plasma exchange, which also costs thousands of dollars in the US. I donate 800 mls a month plasma (25% of my total volume, and another 9% per month when donating platelets., so by week 4 I've replaced 40% to 50% of the old plasma. The Conboy experiment did 50% exchange, once, replacing plasma with saline and albumin. Donation centers do not add back albumin, but do add some saline back. There're indications the effects last at least a month based on what Irina Conboy has said and what she showed in her data. Also James Kirkland has said that senescent cells, when removed, take 2 to 6 weeks to recover. As I am in my late 60s it seems a no brainer to do monthly donation. At a minimum the donations go to a good cause. The only downside for me has been low ferritiin, below the reference range, so I am supplementing iron and monitoring. I am vegan so my iron stores were already on the low side. Also started taking fisetin (natural senolytic per Dr. Kirkland) at 20 mg/Kg of body weight monthly for 2 days between donations.
Peter do you notice any other changes since you started doing plasma donation? more/less energy?
@@rufisdodd4318 Nothing obvious in the way I feel or look. Although I do feel good right after donation. Another person doing similar has reported feeling much better. I do a lot of other things though, so was reasonably healthly before starting. but at 68 yo, I'm mostly gray, so was wondering if over time there might be a little reversal of hair color and maybe some improvements in skin as indicators that real tissue changes were occuring. Irina Conboy said she expected tissue changes to take time, even though she saw reversal of liver fibrosis and senescent cell clearance very quickly. My liver enzymes have been best ever, nearly ideal, and overall blood work very good. Using the Levine DNAmPheoage calculator my age is early 50s so keeping my blood work good should have payoff over the years. I plan to keep doing the plasma and platelet donation on a regular basis and do a better job tracking blood markers, expecially inflammatory markers. BTW, there are plasma only donation centers which allow for 2 donations a week, you can get rid of half your plasma over 3 days, but these centers aren't as common as blood banks and operate by different rules ssince the plasma is not being donation directly to humans as I understand.
@@peterz53 Thanks for the details. We have plasma only centers here, I think they are for profit. Nice thing about that is you don't lose your red blood cells and thus impact cardio performance.
This one reminds me why I'm subscribed to your channel!
newer subscriber here, thanks so much for posting this video
It would be interesting to make a detailed & controlled volumetric analysis using a variety of input factors.
thanks again !
Thank you for the presentation, elucidating this area of research!
The rejuvenating heterochronic parabiosis effect is mainly driven by NAD+ presence (or it's precursors) in the young blood, there is a published research attributing the rejuvenating effect of heterochronic parabiosis to NAD+. Removing Senescent cells in old mice does have an effect but not that drastic, you need to restore the NAD+ level in old mice for the rejuvenation to be drastic and significant.
Thank you very much for introducing and explaining the connection between plasmapheresis and senescent cells. After 5 years of antiinflamatory treatment twice a year with a lot of very good effects I had my first plasmapheresis several months ago at age 67. Incredible subjective changes but I was always worrying about senescent cells buildup and how to counteract. If the well established plasmapheresis would prove to be senolytic, I could avoid the risk of taking little tested senolytics 👍
great infro thanks deeply appreciated success
Very interesting, thank you ! These are in lines with our recently published work too (Krzystyniak et al., 2022, Aging), we also observed a decrease in blood inflammatory factor in the blood of aged D+Q treated rats compare to untreated. Investigating the role of the microbiota at the moment :)
Does donating blood have health effects?
In men lowering body iron is beneficial (many people think).
this was actually hilarious and still educational
UA-cam hasn't showed me one of your video in literally for months and I got the bell icon on.. WTF.
So, it sounds like one of the best things you can do is donate blood and let the body replenish the lost plasma (and cells,etc). Or find a functional medicine Dr that will replenish with saline and albumin but that’s probably beyond the financial means of most. At least on a regular basis. You can donate blood every three months here in the US.
In the US most blood banks where you donate whole blood also solicit platelet and plasma donantion. I donate plasma monthly and platelet two weeks after. Each plasma donation is about 25% of plasma volume. You can only donate whole blood 1x/8 weeks and only loose about 250 mls of plasma, so not as effective as plasma-only donation. Donation is also free.
Have you done a video on the peptide that appears to reverse senescence in vitro? It was discovered by Chinese scientists and I think it was Dr Sinclair who mentioned it in a podcast but I can't seem to find info on this!
9:00 Katcher did the same thing: he gave youth-promoting blood factors to male rats only and it worked (very) well, but a subsequent study with female rats showed (way) lower responses. This difference between the sexes seems to be a common thing, as illustrated by the molecules tested by the ITP that have shown extended male mice lifespan but nothing in females. More diversity in the subjects is better, if you can afford having many animals.
Anyone interested in this topic might find the company Alkahest interesting.
I've watch some of your video and iy interesting but...yes but I like to know what have you learn about youth? Or what can be benefit from these idea that has been given or is it just to many to understand that people lose sign of where life is?
🔥🔥🔥
I still think it's at least partly related to the increasing dysfunction of chaperone mediated autophagy due to a loss of endogenous GLA. I'm nearing 50 and have been taking a lot of Evening Primrose Oil which has a lot of GLA. I'm hoping it's doing something to stave things off. Question is what upstream issue is causing a loss of GLA production? I wish Fisetin ended up being a good senolytic, I have so much left and yet it apparently does nothing according to a recent study.
Eating one meal a day and fasting for seven days every three months would be beneficial.There is a lot of money going into aging research and currently there are160 companies working on different aspects of aging.
I wonder how we could engineer a mouse to have an apoptosis circuit with an operon that requires a cell to be senescent and a synthetic exogenous transcription factor to be present.
Hmm, it would be hard to identify a TF that is specific to senescence, but I like your thinking
@@TheSheekeyScienceShow Thanks!
Fantastic! Do you think the average number of senescence cells found in the blood could be used as a biological aging clock?
So, not the senescent cells (which aren't necessarily blood cells) but protein markers (of which some are secreted by senescent cells) have been used to develop clocks. There is a study that did this in blood to make an inflammatory proteomic clock (iAge); was a Nature paper either 2020 or 2021
@@TheSheekeyScienceShow Thanks Eleanor! Very cool.
I suddenly remember the conspiracy theories I heard as a kid of rich Hollywood stars putting young blood in their veins. 😂
I wonder if there is any risk to a human blood transfusion patient receiving blood from an older donor.
Well, I know the Conboys are currently in the middle of human trials for plasma filtering and reported an epigenetic clock improvement. And Katcher is near the end of a repeat of the H5 formula on rats.
Side note: Why are there no real widespread trials being done with Epitalon if it has been shown to increase the production of telomerase?
So when can I grow new young cloned bone marrow from my stem cells and get myself a marrow transplant?
How often should senescence cells be cleared?
James Kirkland of Mayo Clinic who leads ongoing clinical tests using senolytics says SCs come back in 2 to 6 weeks so monthly seems a good frequency, although I heard one researcher say he uses fisetin every 2 weeks for couple days. Look up interviews with Kirkland on UA-cam.
I think the experiments should be repeated as the statistics arent super strong. But more so seeing this effect of old blood on young mice. I dont understand why the authors of that paper stoped at identifying its in the plasma. The very obvious question is what in the plasma is it exactly. Did they not try to separate it further ? It seems such a obvious thing when one sees this result, one just WANTS to know that more precissely.
And people laugh at blood letting…
out of interest have you heard of “organs on chips”?
i am not a biologist by any means but
from what i hear perhaps they can replicate a human body.
i assume that it could replicate transport between old and young blood between humans rather than doing it on just mice (since AFAIK mice have different bodies to humans)
like to hear your thoughts.
and correct me if i am wrong (which i most likely may be)
"organ on chips" is a good video idea!
@@TheSheekeyScienceShow i am rather surprised that it doesn’t get talked much about, it seems like a really promising venue to me.
i found out about it recently from Aubrey de grey.
i looked up vids about it on UA-cam and many were from a decade ago…
wonder why it doesn’t get discussed…
@Michael Liles shorthand for “as far as I know”
Alexander Bogdanov was right!
As one might expect...🐁🐀
How are people not constantly critical of these studies excluding female mice instead of stratifying results by gender? The hormone-based reasoning generally given is nonsense and the end result of regularly doing this is dangerous for half of humanity, but I mean, whatever. We really need better standards for the funding and publishing of research
-> GHK-cu