49 replies to this topic

[lucid]

How much are they infusing? Are we talking car oil change levels?

[Kalliste]

I think they used a very conservative amount. That is what made me disappointed. When they finally came around to doing something this important I was hoping they would do 20-50 donations but they settled for something far smaller.

[eternaltraveler]

A common misconception is that plasma infusions are inherently safe. They are not. With repeated plasma infusions anaphylaxis and other immune reactions to foreign plasma becomes common. There are reasons plasma exchange is only presently done for extremely severe medical states and monitored closely so potential anaphylaxis can be managed. The benefits of plasma exchange necessarily need to be quite large in order counteract this negative effect. This concern of course does not exist in mice who are almost clones of eachother.

[lucid]

A common misconception is that plasma infusions are inherently safe. They are not. With repeated plasma infusions anaphylaxis and other immune reactions to foreign plasma becomes common. There are reasons plasma exchange is only presently done for extremely severe medical states and monitored closely so potential anaphylaxis can be managed. The benefits of plasma exchange necessarily need to be quite large in order counteract this negative effect. This concern of course does not exist in mice who are almost clones of eachother.

 

I wasn't aware of plasma infusion being dangerous - its not really mentioned in the wikipedia on blood plasma. My reading suggests that its rare. Even so, might be best to pair match a couple of donors with a study participant for the duration of the study so there aren't as many chances for reactions. (If its a rare substance in a few peoples blood that triggers it)

[eternaltraveler]

My reading suggests that its rare

Its not. http://www.ncbi.nlm....d?term=17722046

Further it becomes increasingly common as the procedure is repeated and patients are sensitized to the foreign proteins.

If its a rare substance in a few peoples blood that triggers it

While it's not entirely clear what specific epitopes are most commonly responsible for the most severe reactions there is no reason to suspect immune reactions in general are due to a few rare proteins.

However this is a good idea:

might be best to pair match a couple of donors

As plasma recipients presently receive plasma from pooled sources. The problem is that it's generally not feasible to use plasma from one or a few donors due to the large volume plasma recipients generally require.

Edited by eternaltraveler, 17 November 2014 - 06:54 PM.

[corb]

 

My reading suggests that its rare

Its not. http://www.ncbi.nlm....d?term=17722046

Further it becomes increasingly common as the procedure is repeated and patients are sensitized to the foreign proteins.

If its a rare substance in a few peoples blood that triggers it

While it's not entirely clear what specific epitopes are most commonly responsible for the most severe reactions there is no reason to suspect immune reactions in general are due to a few rare proteins.

However this is a good idea:

might be best to pair match a couple of donors

As plasma recipients presently receive plasma from pooled sources. The problem is that it's generally not feasible to use plasma from one or a few donors due to the large volume plasma recipients generally require.

 

 

If that's the case why are they even considering this as a valid therapeutic option?

The whole thing keeps getting back to what I said couple of months back - this is a complete waste of time and resources - they should just identify the proteins which are promoting the youthful behavior of the cells and if those have the same side effects even when they're synthesized they should just give up on the whole thing until this mechanism is better understood so they can synthesize something else with less downsides.

[eternaltraveler]

 they should just identify the proteins which are promoting the youthful behavior of the cells and if those have the same side effects even when they're synthesized they should just give up on the whole thing until this mechanism is better understood so they can synthesize something else with less downsides.

 

working on it.

 

There are also a few interim things that are less risky that may have some measurable positive effects.

[Kalliste]

Attempts like that are underway for a number of processes. So far those attempts have been hideous failures. It would be nice if these researchers could focus on repair based stuff instead of trying to unwind biological spaghetti puzzles like these.

[lucid]

 

 

My reading suggests that its rare

Its not. http://www.ncbi.nlm....d?term=17722046

Further it becomes increasingly common as the procedure is repeated and patients are sensitized to the foreign proteins.

If its a rare substance in a few peoples blood that triggers it

While it's not entirely clear what specific epitopes are most commonly responsible for the most severe reactions there is no reason to suspect immune reactions in general are due to a few rare proteins.

However this is a good idea:

might be best to pair match a couple of donors

As plasma recipients presently receive plasma from pooled sources. The problem is that it's generally not feasible to use plasma from one or a few donors due to the large volume plasma recipients generally require.

 

 

If that's the case why are they even considering this as a valid therapeutic option?

The whole thing keeps getting back to what I said couple of months back - this is a complete waste of time and resources - they should just identify the proteins which are promoting the youthful behavior of the cells and if those have the same side effects even when they're synthesized they should just give up on the whole thing until this mechanism is better understood so they can synthesize something else with less downsides.

 

These challenges seem surmountable. Here is what I would look to do:

1) Study participant gets 1 unit of donor FFP -> Check for negative reaction.

2) If no negative reaction LINK donor to participant, if negative reaction, do not use donor again for participant

3) Repeat until 'X' good donors are identified. (Where X is the number of units you want to transfuse weekly)

Because donors can (And often do because they get paid) donate weekly, it will be easy to supply participants with a regular supply of FFP for the study from the same donors. This could be done by looking at which donors at a blood clinic donate weekly (historically) or by reaching an agreement with specific donors as part of the study.

 

Also as Cosmicalstorm points out, it would be nice if some low-Tech application like plasma transfusion works in humans without having to understand it yet.

 

[Mind]

https://www.buckinst...-in-parabiosis/ MANF could be another factor for parabiosis rejuvenation (in mice anyway).

[HighDesertWizard]

https://www.buckinst...-in-parabiosis/ MANF could be another factor for parabiosis rejuvenation (in mice anyway).

 

It's about Heat Shock Protein, Mind...

 

Mesencephalic astrocyte-derived neurotrophic factor reduces cell apoptosis via upregulating HSP70 in SHSY-5Y cells

 

Abstract

BACKGROUND:

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a new candidate growth factor for dopaminergic neurons against endoplasmic reticulum stress (ER stress). HSP70 family, a chaperon like heat shock protein family, was proved to be involved in the MANF induced survival pathway in 6-OHDA treated SHSY-5Y cells. However, the ER stress relative transcriptome, in MANF signaling cascades is still investigated. The involvement of HSP70, a 70kd member of HSP70 family, need further to be verified.

METHODS:

The cell apoptosis was assayed by MTT, TUNEL staining and western blot of cleaved Caspase-3. The differentially expressed genes in SHSY-5Y cells under different conditions (control, 6-OHDA, 6-OHDA + MANF) were investigated by RNA-seq. Expression of HSP70 was further confirmed by real-time PCR. RNAi knockdown for HSP70 was performed to investigate the role of HSP70 in the MANF signaling pathway.

RESULTS:

MANF inhibits 6-OHDA-induced apoptosis in SHSY-5Y cells. Six ER stress relative genes (HSP70, GRP78, xbp-1, ATF-4, ATF-6, MAPK) were found enriched in 6-OHDA + MANF treatment group. HSP70 was the most significantly up-regulated gene under 6-OHDA + MANF treatment in SHSY-5Y cells. RNAi knockdown for HSP70 inhibits the protective effects of MANF against 6-OHDA toxicity in SHSY-5Y cells.

CONCLUSION:

MANF exerts a protective role against 6-OHDA induced apoptosis in SHSY-5Y cells via up-regulating some ER stress genes, including HSP70 family members. The HSP70 expression level plays a key role in MANF-mediated survival pathway.

 

[GABAergic]

not news, its been talked about for a while. i just got back to it after reading another recent article on this; https://medicalxpres...oung-blood.html

im considering this though for various conditions. for example, if someone young donates blood and i have it in me, do you guys think it will help rejuvenate me?? also how young is considered most suitable for such thing. obviously its not ethical to have a kid donate blood so i can use, but perhaps a teen is fine too?

[Phoebus]

How would you even get it done? The only company offering it has been shut down as far as I know. 

 

 

[GABAergic]

there was a company offering this service? wow. i missed out i guess.

well, its not simple really. but when i think about this, you do realize there are blood donation centers right? well, imagine some of those places have young healthy people donate and i get their blood. not sure how to control this yet though. its not like i can choose, or maybe i can? i would just have to have a good reason to get blood transfusion is all and then ill figure out how to get specific type of blood in me. it going to be work, but i believe in this as major life quality enhancing idea.

anyway if you guys have any ideas to throw out, please do. im all ears!

Edited by GABAergic, 21 June 2019 - 11:01 PM.

[QuestforLife]

It appears that the benefits of young blood plasma are dependent on autophagy, atleast in rats as reported here:

 

https://www.ncbi.nlm...les/PMC5770779/

 

 

SUMMARY
Recent studies showing the therapeutic effect of young blood on aging‐associated deterioration of organs point to young blood as the solution for clinical problems related to old age. Given that defective autophagy has been implicated in aging and aging‐associated organ injuries, this study was designed to determine the effect of young blood on aging‐induced alterations in hepatic function and underlying mechanisms, with a focus on autophagy. Aged rats (22 months) were treated with pooled plasma (1 ml, intravenously) collected from young (3 months) or aged rats three times per week for 4 weeks, and 3‐methyladenine or wortmannin was used to inhibit young blood‐induced autophagy. Aging was associated with elevated levels of alanine transaminase and aspartate aminotransferase, lipofuscin accumulation, steatosis, fibrosis, and defective liver regeneration after partial hepatectomy, which were significantly attenuated by young plasma injections. Young plasma could also restore aging‐impaired autophagy activity. Inhibition of the young plasma‐restored autophagic activity abrogated the beneficial effect of young plasma against hepatic injury with aging. In vitro, young serum could protect old hepatocytes from senescence, and the antisenescence effect of young serum was abrogated by 3‐methyladenine, wortmannin, or small interfering RNA to autophagy‐related protein 7. Collectively, our data indicate that young plasma could ameliorate age‐dependent alterations in hepatic function partially via the restoration of autophagy.

 

So this links the benefits of CR, intermittent fasting, rapamycin, glucosamine, etc., to young blood. It is likely that when you mix your blood with younger blood, you get more favourable conditions for the upregulation of autophagy.

[Mind]

The scientific term is parabiosis. "Ambrosia" was the company offering this service. Not sure whether or not they are still operating:

 

https://www.business...ambrosia-2017-1

 

https://www.longecit...tion-of-damage/

 

https://www.longecit...venation-trial/

 

 

[QuestforLife]

The scientific term is parabiosis.

 

Actually parabiosis is, I believe, when two unfortunate animals of differing ages have their circulatory systems stitched together.  So they share everything that's in the blood.

 

Young plasma is the cell free part of blood that supposedly contains rejuvenating factors.

[Mind]

Actually parabiosis is, I believe, when two unfortunate animals of differing ages have their circulatory systems stitched together.  So they share everything that's in the blood.

 

Young plasma is the cell free part of blood that supposedly contains rejuvenating factors.

 

Yes, that is more correct.

 

Thanks for pointing out my oversight/misstatement.

[Bruce Klein]

According the Feb 2019 NBC article, Ambrosia “ceased patient treatments" in the United States after the FDA Commissioner Scott Gottlieb, M.D. (with others) issued a joint statement warning consumers there is no evidence for treating various conditions with young donor plasma. 

 

However, as Mind suggest, not sure if Jesse Karmazin (Ambrosia CEO) continues to do this in the US or other parts of the world, as their website still has the offering -- 1 liter for $8k and 2 liters for $12k. 

 

https://www.ambrosiaplasma.com/

 

https://www.nbcnews....warning-n973266

 

https://www.fda.gov/...valuation-and-0

[GABAergic]

wow its really expensive. cant i just get young blood plasma without dealing with third party? i mean, i can find a young donor, he can donate for me and i get the blood. of course ill pay him/her for it. teenagers do need money after all. it shouldnt be difficult