Looking for partner or group for DIY TPE

[Frank]

Recent published experiments like the one below from UC Berkeley, demonstrate multi-system rejuvenation from an existing widely available procedure, therapeutic plasma exchange TPE.  This is quite exciting and the paper is well worth reviewing. I am interested in begin able to perform TPE on myself with someone's help. If you are interested please let me know.

https://www.aging-us.com/article/103418/text

[Raph N]

Hi Frank,

Great minds think alike, I'd love to test that, especially with an epigenetic age test to quantify the rejuvenation potential.

Where about are you?

I'm in the UK.

Raphael

[Frank]

Hi Raphael,

An epigenetic age test sounds pretty sophisticated. would love to learn more about that. Is it a standard lab test I can order?

I'm in New York City.  I learned a little more about doing this which opened up an unexpected avenue and more questions

1. Since the discovery and validation of young blood transfusion rejuvenation efficacy, studies like the recent UC Berkeley paper figured out that the effect comes less from gaining systemic factors in the young blood than from loosing detrimental factors in the old blood.

2. The key to the rejuvenating effect of the therapeutic plasma exchange TPE/plasmapheresis is eliminating 50% (less is Ok  though not optimal) of the older subject's plasma. Plasma constitutes around 60% of total blood volume, so removing 50% means 30% of total blood volume. For my size that equals about 3.4 liters!!. That would result in potentially catastrophic blood pressure drop so it has to be replaced by isotonic saline and it has to be done incrementally if you don;t have a continuous centrifugal separation apheresis machine which is very pricey.

3. One question I have is if the saline can be taken orally? would the body not absorb the solution just the same as intravenously albeit more slowly?

Thus doing this myself is out of the question. I would need at least one other well-trained person present. in looking around  for labs or service providers that offer TPE I stumbled upon blood donation. When you dontse blood nowadays you get choose the type of donation: Whole blood, RBC only, Plasma, or platelet. Well sure enough the way the blood bank takes a plasma donation is by using plasmapheresis, ha! So by donating plasma you get a rejuvenation treatment for free.  The main drawback is that they only take a pint of plasma which is about half of the optimal 50%.  So I am scheduled to do this early next week.

[Raphael Nicolle]

Hi Frank,

Yes this study is quite intriguing, but they did not use a global test to quantify the systemic rejuvenation, so it is hard to evaluate exactly what happened. That's why I want to use an epigenetic age test. Yes, those are fancy and quite expensive (starts at 300 usd/ test with the cheapest provider), but they are the gold standard to measure biological age, and thus evaluate more precisely how effective the procedure is. You can read about epigenetic clocks here: https://nintil.com/epigenetic-clocks

I don't think you could remove blood and replace orally by saline. I don't have good evidence for or against but I wouldn't try it. Anyone else knows more about it?

Regarding blood donation yes plasma donation is the closest you can come with. I don't have access to that in the UK (you can only give whole blood or platelets). In the US it's even better than free you're paid a little for it, I think, and you can give plasma twice a week. If you do it, it would be great if you were able to be able to quantify the effect a bit. I'm not sure a whole epigenetic test is worth it though; if it were really that powerful, we would have noticed. Or maybe there is a threshold effect somehow where 25 is not enough to trigger whatever it is that happens?

Anyway, keep us updated.

On my side I will try to find a clinic and MD to do it, or worst case organize a small clinical trial. Or we might as well wait for the UC Berkeley team to complete their own clinic trial :)

Best regards,

Raphael <raph...@gmail.com>

Tel/Telegram/Whatsapp: +447399 108 586

Skype: raphfinex

https://calendly.com/raphaelnicolle

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[Gary Dale]

So, how is the Conboy NBE or TPE any different than just donateing blood or just plasma? Seems to me it's exactly the same except the Conboy's have discovered a NEW Anti Aging benefit. That of flushing out years of accumulated garbage (maybe broken components that the liver/kidneys can't filter out?). You don't replace 50% of your plasma at once but donating 1 pint of blood with 8 weeks between donations should add up :-)

[Frank]

So far here is what i have surmised. The amount of blood taken during a donation varies by donation type, your height and weight, and the donation center. Donations are not supposed to exceed 15% of total blood volume but can be twice that for plasma depending on the individual donor for plasma. when you donate whole blood, the 1 pint or about 1/2 liter taken includes all components. if 60% is plasma that's  262 ML 7.8% of your plasma. When you donate plasma, the pint taken is all plasma so that's 15% of your plasma becasue the other blood components are re-infused.  One reason more total volume can be taken with plasma vs whole blood is that with whole blood there is no volume replacement whereas with plasmapheresis the volume of plasma taken is replaced with saline. So depending on the blood collection center you can ask to donate up to a liter of plasma which is about 30% of your plasma. that starts to approach the promised land.

But wait there's more! Whole blood donations can't be more frequent than once every 4-6 weeks or even longer for some places. But you can donate plasma once every 7-10 days. So in 7 days with two donations you could get very close to the mice in the experiment. The only thing that sucks is getting so much anticoagulant  infused.

[Frank]

oh yeah those numbers are for me based on a total blood volume of 5.73 liters

[Raphael Nicolle]

There may be a kind of threshold effect to get the expected benefits.

It may also be that there will not be that much rejuvenation going on, see for example this article: https://joshmitteldorf.scienceblog.com/2020/06/29/human-trials-of-plasma-exchange/

Cheers

Raphael <raph...@gmail.com>

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[James Clement]

Betterhumans has been looking at running an IRB-approved clinical trial using TPE for several years (we have run a half-dozen different antiaging clinical trials since 2016 and intend to run about eight in 2021). I was part of a small group that approached Dr Dobri Kiprov in 2014 to arrange for a TPE clinical trial, but he wanted $25,000 per patient for a single treatment. We have since done a lot more research on recurring TPE therapy and believe we can do far more cheaply than this, but there are lots of potential risks and side effects if you try to do it too frequently. Since Betterhumans is opening its own antiaging clinical trial medical office in the near future with our own medical staff, we have been waiting until it is operational to pursue this particular clinical trial further. Of course the latest Conboy paper only strengthened our desire to test this in elderly subjects, when we are set up to proceed. We also have all of the analytical instruments in our laboratory to determine whether it works (including an Illumina iScan sequencer to run Infinium 800k beadchips, the only validated method for the Horvath clocks, with whom we're collaborating).

I don't know you or the others who have responded to this personally, but assuming you are not in your mid 60s or older, I would highly recommend that you do not attempt to DIY this yourself. If you're under 50 then you have plenty of time to wait for multiple clinical trials to prove the real-life efficacy and safety of TPE for antiaging purposes, and work the kinks out. We are finding there are downsides and risks to all of the antiaging therapies we have tested so far, and at least for the time being they should be reserved for those who simply can't wait the 10 years or more for them to be properly tested and optimized.

Best regards,
James 

[Frank]

James,

Thanks for the response.  I am actually close to 60. Unless I find a plasmapheresis machine for free I will likely not attempt this myself mainly due to the impracticality of extracting the amount of plasma needed manually/incrementally. I actually have an educational background in medicine though I am not a practicing physician. The avenue that I thought might be useful is donating plasma which amounts to a TPE treatment though the volume taken is still inadequate. I had bad luck trying that yesterday as I was turned away for not having an AB blood type. After looking into it I was told this was a mistake and that I should be able to donate so I will try again next week. If you are looking for trial subjects by all means sign me up.

[Gary Dale]

I am in my 60's and am considering donating plasma or blood also but want to try and verify if there is any rejuv. I am looking into epigenetic age tests that are available to run BEFORE donating and then after some number of donations.

This is my first day researching it but this kit seems interesting and not too expensive.

https://epiagingusa.com/product/epiaging-kit/

[Frank Garcia]

I don't know too much about the epigenetic tests however it might be useful for you to take a look at the biomarker tests that were used in the experiment that I posted which started this discussion. They did pretty rigorous testing of multiple systems and tissues to determine efficacy.

[Raphael Nicolle]

The problem with the biomarkers used in the experiment is that they can't prove rejuvenation.  For example we know exercise improve lots of biomarkers, yet it does not rejuvenate you, or you could exercise your way to immortality. 

As far as we know epigenetic clock is the best marker of biological age. 

Raphael <rap...@gmail.com>

On Tue, Jun 30, 2020, 01:50 Frank Garcia <fgarc...@gmail.com> wrote:

I don't know too much about the epigenetic tests however it might be useful for you to take a look at the biomarker tests that were used in the experiment that I posted which started this discussion. They did pretty rigorous testing of multiple systems and tissues to determine efficacy.

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[boj Ko]

It's a long way to go, if anything! - Are you ready for it?
First you need to go through a synergistic detoxification for about 5-6 months, then go through the enrichment of a number of organs with new cells through stimulation systems and only then begin invasive measures to influence long lengths in complex ways. (Whiskey and almost all delicious food and not only will leave your life for 7 years) Otherwise, the results will stagnate)))) Are you ready for this))))

вт, 30 июн. 2020 г. в 09:20, Raphael Nicolle <rap...@gmail.com>:

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[Raphael Nicolle]

What are we looking at? What's the image saying?

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[James Clement]

Proprietary tests that haven't been validated independently (peer-reviewed and duplicated in other labs) are nice tools for doctors to convince their patients that whatever they're doing is working, but aren't useful scientifically. The same is true of cheap telomere tests, or other purported proprietary biomarkers, IMHO.

Cheers,
James

[Raphael Nicolle]

That's true enough about commercial test, though there's an easy way to check their validity: Don't give the company your age, and see how accurate the results are.

However I still believe that in principle epigenetic age are the best marker for age. That it is hard to test doesn't change the results. In fact, if you want to be accurate, you can contact Steve Horvath and get his help for the testing. That's what I'm working on for stem cells and exosomes with a few test patients.

Cheers

Raphael <raph...@gmail.com>

Tel/Telegram/Whatsapp: +447399 108 586

Skype: raphfinex

https://calendly.com/raphaelnicolle

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[Frank Garcia]

I guess we need to define rejuvenation then. the biomarker tests in the experiment each measures one tiny piece of the physiological state which, depending on the direction in which the marker changed, indicates a physiological state that more closely resembles that of a younger organism. I'm not sure (maybe i'm wrong) there is a universally accepted definition of rejuvenation. and there certainly isn't any single market that proves rejuvenation. It's simply too complex for that to ever be the case. It's more like pick your basket of markers of aging and test them over a period of time and see which way they are heading.  I personally think any markers of rejuvenation has to include those that measure the physiological dirvers of age -related disease and deterioration such as insulin sensitivity, fibrotic markers, resting heart rate, muscle stem cells, mitochondrial markers, cholesterol trajectory, cardiac output efficiency, C-reactive protein, just to name a few out of a million.  In the study, muscle anabolism vs catabolism is in fact a good aging biomarker

[Frank Garcia]

As far as whether proprietary tests of epigenetic changes are the way to go I think that for measuring whether "rejuvenation" has occurred we don't need to spend a bunch of money or get too fancy. Just look in the mirror, so to speak.  If I am being rejuvenated then that's going to be reflected in my blood pressure, exercise capacity, sleep patterns, LDL, bone density, GFR, etc. So the standard diagnostic lab tests will reflect those changes.

[Frank Garcia]

FYI: interesting aside on the commercial interest/viability of TPE. About 4 years ago I had a conversation with a medical student in California who just started a company called Ambrosia to sell young blood transfusions under the guise of a clinical trial . for $8000 they would give you 3 transfusions of young blood plasma obtained from a blood bank. He claimed they had a waiting list. I just checked in to see how that went: https://www.ambrosiaplasma.com/ . Apparently not so bad. I think I'll give the guy another call to talk about TPE as a commercial private service.

[Raphael Nicolle]

That's a good point, what is rejuvenation? 

For me it's the actual "running back" of the body clock. To qualify as rejuvenation, an intervention should be able to postpone indefinitely aging if repeated sufficiently enough. So it's different than just doing exercise and be in better shape for example.

I have a problem with general biomarkers like insulin sensitivity etc,... The reason is basically this: https://michaellustgarten.com/2020/06/26/blood-test-analysis-in-a-100-year-old-subject/ If you look at the blood work of this subject, it would quite good even for a 40 year old. and yet, I'm certain if I see this subject, I will know right away he/she is definitely NOT a 40 years old. 

So we need a biomarker that is as closely related to chronological age as possible. And, for all its potential implementation issues, epigenetic age is so far the closest to the mark, with a correlation of 0.94 or even better for the latest peer-reviewed iterations. That's fracking good. And it's not just a "single" biomarker, it's a composite from hundreds of methylation sites across the genome, corresponding to hundreds of different gene expression changes.

Now the mirror test is a good one, but it will take a pretty good effect to show up with confidence, something I'm not sure TPE would do (or we definitely would have heard about it).

Anyway, multiple approaches are good, and I agree those fancy tests are expensive still :)

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[Frank Garcia]

Actually it isn't chronological age that we want to measure. we know how old someone is. we want to measure biological age. and that is contributed to by a huge number of variables. biological age means health. think of this as a myrid of axis or spectrums gradually change as we age, from the elasticity of your blood vessels, the levels of metaloproteinases you produce, the amount of senescent cell populations in your body, how much  advanced glycation end products you have accumulated, hormone levels such as growth hormone, androgens, and klotho, just to name a few out of thousands. moving the needle backwards on those axes makes you younger. But can any single test or type of test give an accurate reflection of that?

[Raphael Nicolle]

• Epigenetic age test is an aggregation of hundreds of methylation sites in the genome, tracking change in expressions of many genes (involved in multiple pathways then).
• It correlates extremely well with chronological age (r>0.9).
• BUT it is amenable to some interventions which causes a lower epigenetic age, which also matches other biomarkers you cite such as fasting glucose, senescent cells, mitochondria output,... 
• In fact most* hallmarks of aging, as measured by other means, do correlate with this epigenetic age result as well, whether it matches chronological age or it is substantially lower (or higher for that matter).
• We can also reset the epigenome using a set of genes (the 4 Yamanaka factors), which gives a cell that is biological as young as we want (all the way to embryonic), with an epigenetic age of 0, and a fully functional embryonic phenotype. Or whatever the "clock" was stopped at.

I don't know what you conclude from these facts, but personally, I conclude that we have a serious contender to a very accurate age marker.

*I say most and not all because the rest haven't been formally studied, not because they do not correlate to epigenetic age as well. 

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[Frank Garcia]

sounds like the epigenetic tests may in fact reflect physiological status not just passage of time. i'm going to read up on this a bit. 

[Raphael Nicolle]

Yes this is what I think. Hopefully commercial applications democratize soon enough :)

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[Raphael Nicolle]

https://nintil.com/epigenetic-clocks

[Frank Garcia]

Can i summarize what we've all said here about testing this way:

1. we want to know if an intervention is effective

2. so we want to test rejuvenating changes in physiology

3. real benefit should be detectable and demonstrable with

                - increases in physical capacity

                - improvements in metabolic and other physiological end products and systemic biomarkers

                - changes in gene expression marked by epigenetic changes

4. thus to have a good sense of the effect an intervention has had we can't use just one type of test. We should employ multiple types of tests that include a selection from at least these three categories

                - exercise capacity, BMI, resting heart rate, blood pressure, sleep patterns, bone density, etc.

                - molecular marker of glucose, cholesterol, inflammation, GRF, CRP, fibrosis, etc

                - epigenetic markers such as methylation levels and other gene expression markers, mitotic competence

[Gary Dale]

I am no expert but seems to me (as a DIYBIO enthusiast) that TPE might not produce a complete a flush as a plain old blood donation.

MY understanding of TPE is that the plasma is separated out by centrifuge separating ALL heavy particles....blood cells and junk to be returned to the donor, thus putting all the particulate garbage back in to you... not actually ridding it from the body as in a blood donation  :-)

COMMENTS...IDEAS... CORRECTIONS...?

[Frank Garcia]

Not exactly that way Gary. Plamsa is the the thing you want to eliminate, not RBC or platelets. in TPE, plasma is extracted and not returned. Also, the volume of plasma that is taken is replaced with saline solution. this and the return of the rbc allows for extracting significantly more plasma than with whole blood donation. and the goal is to lose up to 50% of plasma.

[Raphael Nicolle]

Yes Frank that's my understanding as well :)

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[Gary Dale]

Thanks Frank, I think you're right.

I reviewed the conboy article and their quote: "a single TPE yielded functional blood rejuvenation" says you don't need a whole blood donation.

They seem to believe their NBE/TPE yielded "significant dilution of autoregulatory proteins that crosstalk to multiple signaling pathways".

Apparently  the centrifuge step to separate out the plasma does not remove ALL particles from the plasma.

But I think they are removing platelets with the plasma because they refer to the plasma as PRP:

"Specifically, we performed a “neutral” blood exchange (NBE) by replacing the platelet-rich-plasma (PRP), fraction with physiological saline"

[Frank Garcia]

Gary,

Right, the point is you do not take whole blood, just plasma, otherwise you wouldn't be able to take the needed amount of plasma.

Thanks for pointing out the PRP. I missed that. I'm going to have to back and read again to see if they consider platelets to be the source of some of "the bad stuff".  However they also say that their procedures is the equivalent of TPE which does not take platelets, right?

[Frank Garcia]

Quick update about obtaining TPE.

So I went to the blood center in NYC and donated 800 ML of plasma which they replaced with saline but no albumin. It was a TPE process like in the paper I posted here but with only about 25%, half of the ideal 50%, plasma dilution and no added 5% albumin. They will not take more unfortunately. and i have to wait 28 days to donate again.  I'm thinking there should be dose-dependent benefit?

I thought I would be able to do the same with a different blood donation org like red cross who wouldn't know I just donated but they have no locations in NYC and they only take plasma donation from people with blood type AB. I have O. Looking for other blood banks that take donations.

[dale]

So Frank... do you feel younger today?

Did you get any kind of biomarker or epigenetic age test before?

I would not look for another TPE too soon. The blood center probably requires 28 days for important safety reasons (they should know being that blood is their business).

I don't think the conboy article mentioned any dose dependent or time requirements. To me it seems if you flush 25%  or even 10% of the old garbage each time, it should still be the positive effects they claim, but cumulative.

My household doesn't care if the trash goes out all at once or in 4 or 5 trips... just so it goes :-)

[Raphael Nicolle]

Well, it is possible that the effect is cumulative but depends on the % of plasma replaced. And we need to quantify the effect so that we know how frequent the need for plasma dilution should be. Who knows, it might even be possible to reach longevity escape velocity, if it turned out that there is actual and cumulative rejuvenation going on (though the effect, if it exists, is probable small enough that we need a big sample size).

But yeah, be safe Frank. You might wait for 25 days before the next. Then 20 days,...

Cheers

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[Frank Garcia]

true. good advice. i did not have tests performed party due to expense. Not sure how many of you are the the US, but here even if you have so called insurance, it doesn't cover testing beyond the standard old blood tests . If anyone has suggestions for how get relevant biomarker tests cheaply please let me know.

[boj Ko]

Mr. Frank Garcia   - I can help you a little with my little knowledge on the methods of invasive effects on the metabolism in the body.
As far as I know, in an ordinary person, increased neurogenesis was associated with the enrichment of the intestinal microbiota with butyrate, a short-chain saturated fatty acid. 

ср, 8 июл. 2020 г. в 20:49, Frank Garcia <fgarc...@gmail.com>:

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[dale]

While your post is interesting, I am wondering if you posted to the wrong group? This group is discussing DIY TPE relevant to the Conboy article.

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[dale]

Frank are you feeling any younger yet?

Still planning a 2nd plasma donation?

I have started researching Epigenetic age tests but have not had much free time recently.

Does the boj Ko post belong in a different group?

[Frank Garcia]

Dale,

 Are you saying the discussion about TPE is not appropriate for DIY Bio?

[Frank Garcia]

I'm spacing out on boj ko post. is that my post?

[dale]

Hi Frank... thats what I was saying... the boj Ko post seems not appropriate for this DIY TPE conversation. I think it was posted in the wrong group.

[Frank Garcia]

Oh , yes right.  probably wrong group. Is there a DiY or biohacking group focused on anti-aging?

To answer your previous question, yes I am scheduled to donate plasma again on August 3rd. I hate missing the opportunity to measure this objectively with some testing before and after.  I'm going to try and an rx for basic blood work that includes some of the more relevant markers. In case I can slip in some epigenetic or other tests like the ones we've been discussing that insurance will pay for, does anyone here have any specific suggestions for tests that are currently available form places like labcor or quest?

What tests are analogous to the measures used in the Berkeley paper?