81 replies to this topic

[PAMPAGUY]

 

 

 

 

 

 

I just took 1500 mg. 1 hour ago.  Probably took too much, but 1500 is within the range of doses prescribed.  My plan is to take 1500 mg once a month to clean out the senescence cells, and do it again every month.  500 mg. is probably sufficient because in the paper they said a solo low dose was used.  It comes in 250 and 500 mg.  I paid 3.50 Euros for 3 x 500 mg.  At 72 yo, hoping to feel something.  

Buying in Spain was very easy.  Showed them what I wanted and had it in 1 minute. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

[PAMPAGUY]

Here is the latest paper on clearing out senescence cells.  At end of paper it has a list of supplements that do not work.  They tested them all in vivo.

This could be it.

 

 Posted Today, 11:59 AM

I just read the paper and was really impressed.  Have been waiting for some results from all the work being done on senescence, but no one could get around harming healthy cells while clearing out the bad one's.  This is the next big treatment on ageing that everyone has been waiting for.   I live in Spain and can get it without Rx.  50 Ul no effect, 100 Ul great effect. (anyone convert this to a human dose)  They said one (1) low dose was all that was needed.  Low dose is what?  I have seen doses from 500 mg to 2000 mg online for different conditions.  I think I will try 1500 mg once.  ( believe it takes bad cells time to build up again) Azithromycin has a long half-life, FDA approved, and inexpensive.  Pharma will try and bury this.   If you could take it once every 3 months that would eliminate any chance of drug resistance.  Really don't know dosing amount.  Dosing schedule is one dose, but how often.  (Once a month, 3 months, 6 months)  Seem's very low risk with a big upside, so will try.

 

Any feedback is appreciated.  Here is one write up on the paper that condenses the major points.  The open source paper is at bottom.

 

https://medicalxpres...PmfNKq7VyBWp6xw

 

[sphere]

you may well cause yourself problems based on a very basic mis-quote from the study

>> 50 Ul no effect, 100 Ul great effect. (anyone convert this to a human dose) <<

 

that is not accurate the correct is >>At 25 μM, Azithromycin did not show any effects on OCR. However, at 50 μM, the effects of Azithromycin clearly inhibited mitochondrial metabolism, especially effecting maximal respiration and spare respiratory capacity. In contrast, at 100 μM, Azithromycin actually stimulated maximal respiration and more than doubled spare respiratory capacity. This may represent a cellular compensatory response to Azithromycin treatment, to overcome its mitochondrial inhibitory effects.<<

 

UI is NOT the same as  μM. Note the difference re the concentrations. Based on that you may cause yourself problems as u have no idea at this point re dose in reference to  eliminating senescent cells . Why not wait until you establish some ratio between the dose used and a human correspondence  [some math based ratio models have been suggested on this forum: perhaps others can suggest in this case]

 

one dose of 1500 mg should not cause harm [other than to possibly negatively  effect your gut balance] but my suggestion would be to go back, read what Reason had to say, and at the very least get a idea of dose based on μM mouse to a corresponding human dose.

 

just mo

Here is the latest paper on clearing out senescence cells.  At end of paper it has a list of supplements that do not work.  They tested them all in vivo.

This could be it.

 

 Posted Today, 11:59 AM

I just read the paper and was really impressed.  Have been waiting for some results from all the work being done on senescence, but no one could get around harming healthy cells while clearing out the bad one's.  This is the next big treatment on ageing that everyone has been waiting for.   I live in Spain and can get it without Rx.  50 Ul no effect, 100 Ul great effect. (anyone convert this to a human dose)  They said one (1) low dose was all that was needed.  Low dose is what?  I have seen doses from 500 mg to 2000 mg online for different conditions.  I think I will try 1500 mg once.  ( believe it takes bad cells time to build up again) Azithromycin has a long half-life, FDA approved, and inexpensive.  Pharma will try and bury this.   If you could take it once every 3 months that would eliminate any chance of drug resistance.  Really don't know dosing amount.  Dosing schedule is one dose, but how often.  (Once a month, 3 months, 6 months)  Seem's very low risk with a big upside, so will try.

 

Any feedback is appreciated.  Here is one write up on the paper that condenses the major points.  The open source paper is at bottom.

 

https://medicalxpres...PmfNKq7VyBWp6xw

 

 

[Hebbeh]

https://www.longecit...o-be-senolytic/

[Oakman]

Quite a development, this. The list of ineffective compounds is as well > https://s3-us-west-1...uFq34BD_sd1.pdf

 

OP2040, is it really that easy to get Azithromycin as it appears on that site? Chat with a doc online, get a prescription, order it? I've never done anything like that. Not cheap.

 

If it works in vivo, at least we'd have good skin and lungs afterwards, free of senescent cells...i.e., lol, so I guess young looking old people with renewed skin and lung capacity. All other tissues as yet unknown.

 

Wondering how this affects the holistic body, microbiome especially. I try never to take antibiotics just for this reason. It's too easy to knock your internals to a state of uncomfortableness just thru normal living.

[OP2040]

It has to be said, we are well on our way to conquering this hallmark of aging.  But it begs the question, how can we really know.  We have plenty of potentially successful interventions but we are still flying blind.

 

To wrap this up we NEED testing.  This would allow us to make the most effective intervention at the most appropriate time.  The biggest problem with this is the diversity of tissues involved.  But if it could be established that the senescent cell burden in all tissues was relatively stable in relation to each other, then you could perhaps use a skin sample to take a baseline and continuous monitoring.  I'm seriously considering waiting for a bit and trying this with the SA-B-Gal assay.

 

Anyone else interested in trying this with me and taking the whole thing to the next level? 

[StanG]

chewy.com requires a vet's approval

[sphere]

to consider

 generic [same as] the generic Azee is available as an injection. That may eliminate some of the possible negative side effects re effecting "good" gut bacteria, an injection would side-step that]

https://www.medplusm...ECTION/AZEE0008

 

generic also of course as a capsule/tablet---Generic and cheap of Azithromycin is Azee: https://www.practo.c...-mg-tablet-1018

[xEva]

 

Here is some of the information that I've collected. Does anybody know any sites I could go to buy Azithromycin without a prescription? At 138lbs, I think 250mg should do it - any thoughts?

 

So I would opt for 50 uM concentration. Converting that molar (at MW 192.25) to a mg dose diluted in my TBW (calculated at 36L) would suggest a dose of ~350 mg. In a PK study of Azithromycin, a 500 mg dose given humans of comparable size to me daily for 3 days resulted in peak concentrations of 400 ng/ml (plasma) and 25 ng/ml (subQ and muscle) tapering to 100 ng/ml and 10 ng/ml by hour 10 each day.  That matches pretty nicely with the 9.72 ng/ml I extrapolated from the study. So, assuming my current load of senescent brain cells hasn't buggered up the math (no guarantees here), 500 mg would work for me. 

But for how long? The in vitro study  tells us Azithromycin killed 70% of senescent cells after 5 days. Combine that with the PK data in humans. So maybe 3-5 days of senolysis. Then 6-8 weeks of recovery or senomorphics and tissue reconstruction precursors alone. Then remeasure.  I'm working on a viable, scalable. cost efficient measure of senescent load. Wish me luck.

 

Very interesting. Thanks. Just to point out that the molecular weight of azithromycin is much higher than quoted. It’s 749 which will have a big impact on the dose calculations which were based on a number about 4 times lower (192).

 

 

AZ was senolytic at 100 µM, it had nos enolytic effect at 50 µM, and if you look at the graph (Fig.5), you will see that, after 5 days, at 50 µM it actually increased the number of senescent cells.

 

Also, AZ molecular weight was quoted at 748.996, which is what you have too.

 

And then you don't seem to consider 37% bioavailability of AZ, when taken PO, (see pharmokinetics study quoted above).
 

[xEva]

to consider

 generic [same as] the generic Azee is available as an injection. That may eliminate some of the possible negative side effects re effecting "good" gut bacteria, an injection would side-step that]

https://www.medplusm...ECTION/AZEE0008

 

generic also of course as a capsule/tablet---Generic and cheap of Azithromycin is Azee: https://www.practo.c...-mg-tablet-1018

 

 

That's in India and Burma and the prices are in local currencies. I'd be curious to know if you succeed. And yes, injectable form is better.
 

[xEva]

 

Here is the latest paper on clearing out senescence cells.  At end of paper it has a list of supplements that do not work.  They tested them all in vivo.

 

not in vivo but the same in vitro assay -- and! the list of Ineffective compounds includes dasatinib (at 0.1 -1 μM) and quercetin (at 10 - 100 μM)

 

dasatinib ineffective senolytic -- how about that?

[StanG]

azee is quite expensive for tablets!!!

[PAMPAGUY]

That's in India and Burma and the prices are in local currencies. I'd be curious to know if you succeed. And yes, injectable form is better.
 

 

I just purchase 3 tablets Azithromycin 500 mg for 4 euros here in Spain.  I understand it is cheaper in US.  One suggestion:  Tell your Doctor that your traveling overseas to Mexico, etc., and would like an antibiotic just in case.  Should work to get Rx.    Used here for travel diarrhea. 

 

So what is the single dose that you would suggest in that the recommendation is for 1 low dose as set forth here?       

 

https://medicalxpres...PmfNKq7VyBWp6xw

 

Of course, I would like to make sure that I get the proper concentration without over doing it.  My plan is to take a strong enough dose once a month to clear out the Senolytic cells, and do it again once they have build up again. (How long does it take to repopulate?)  Could be any time frame.  Anyone got any knowledge on this?  Half-life is a long 67 hours, will stay in system for almost 7 days.

 

I can understand everyone's reluctance to use this because of killing the gut bacteria, but when your a healthy 72 yo, but dying slowly this is a big deal.  Senolytic's is probably the number one or two reason we age.  This is a very big deal.  No one has found a drug that would clear out the zombie cells without harming the good one's,

 

Would only recommend this for someone over 60 yo who don't have much to lose.  Younger people don't need it for ageing.

 

Anyone wanting Azithromycin could contact dropshipmd.com in India.  They supply me with Rapamycin and have been very happy.  Had no problem getting it from them when I was in US.

[PAMPAGUY]

this would be interesting to test on skin

https://www.ncbi.nlm...pubmed/15370397

 

Unfortunately only on pre-sription here

 

@pampaguy as I am in the EU too I should be able to buy it from Spain, would appreciate if you could point to a seller?

 

Just purchased it here in Spain for 4 Euro's for 3 x 500 mg.  It is sold without an Rx here.  It is used mainly for travel diarrhea.  You should tell your Doctor in US to Rx for that reason.  You'll be traveling to Mexico, etc., and want a back up just in case.  Done all the time.  It is very inexpensive in US.

 

I just took 1500 mg on Saturday, on an empty stomach and will see how I feel.  Will probably drop down to 500 mg x once a month.  Idea:  Wipe out senescence cells, and wait for them to repopulate the mitochondria then do it again.  Next dose for me is 500 mg. Jan. 1, 2019.

 

Any suggestions on dosing schedule would be appreciated.  I'm a health 72 yo, but going down hill no matter how much I exercise and eat properly.  This is a very low risk protocol, but should probably only be used by people over 60 yo. with very little to lose.

[Rocket]

I have taken plenty of z-packs in my life and never noticed a damned thing. Most of the USA has probably take a z-pack and I don't know anyone reporting feeling younger or healthier afterwards. You would think if it truly wiped out 97% of the senescent cells someone would have noticed.

A moderator needs to close this thread or move it to supplements.

Edited by Rocket, 03 December 2018 - 01:16 AM.

[xEva]

I have taken plenty of z-packs in my life and never noticed a damned thing. Most of the USA has probably take a z-pack and I don't know anyone reporting feeling younger or healthier afterwards. You would think if it truly wiped out 97% of the senescent cells someone would have noticed.

A moderator needs to close this thread or move it to supplements.

 
 
I think this may have to do with a rather high concentration, at which AZ becomes senolytic to lung fibroblasts. There was no senolytic effect on this cell line at half the strength. I doubt a concentration this high can be maintained in vivo -- for 5 days! Certainly not without worrying side effects.
 
I was also intrigued by this:
 

the mitochondrial effects of Azithromycin were concentration-dependent and bi-phasic. At 25 μM, Azithromycin did not show any effects on OCR. However, at 50 μM, the effects of Azithromycin clearly inhibited mitochondrial metabolism, especially affecting maximal respiration and spare respiratory capacity. In contrast, at 100 μM, Azithromycin actually stimulated maximal respiration and more than doubled spare respiratory capacity. This may represent a cellular compensatory response to Azithromycin treatment, to overcome its mitochondrial inhibitory effects.

 

it's tempting to speculate that AZ's senolytic action after 5d at 100 μM was the result of the mitochondrial damage senescent lung fibroblasts sustained  -- sorta could not take it anymore -- as if the cells had to resort to glycolysis, because their mitochondrial function was seriously impaired. And after a while, they had to either overcome it or perish. Strong autophagic action is what allows a cell to survive. It appears normal cells managed this feat while the senescent cells could not. This may imply that AZ acts as a hormetic agent -?
 
 
Interesting that "Azithromycin was more potent in BJ skin fibroblasts, showing significant “senolytic” activity at only 50 μM." Not only that::
 

Remarkably, Azithromycin also increased the viability of normal BJ skin fibroblasts, by > 25%.

 
This is illustrated in Fig.10 -- which leaves me perplexed. It seems AZ stimulated proliferation in normal skin fibroblasts -?  How else to explain the increase in the percentage of normal cells  to well over the 100% mark -?   Take a look.

 

 
PS
StanG@ -- now I understand why you opted for 50μM concentration. Sorry, when I first read the paper, I skipped the part about the skin fibroblasts and only followed the lung line.
 
It also occurred to me that in their "list of ineffective compounds" they should have stressed, "ineffective on human fibroblasts". .Different senolytic compounds appear to be  tissue-specific. That was the case with quercetin and dasatinib. And now, AZ.

Attached Files

•  fig10.jpg   73.05KB   0 downloads

Edited by xEva, 03 December 2018 - 04:56 AM.

[Turnbuckle]

A crude calculation of dosage, given—

 

A — Water in a human body — about 48 liters for a 180 lb person.

B — Azithromycin molecular weight of 749 g/mole.

C — Desired in vivo concentration of 100 μM (.0001 mole/L).

D — Azithromycin bioavailability of .37 (no units).

 

Dosage = AxBxC/D = 10.8 g

 

That seems potentially dangerous. So one might look for synergistic effects to reduce the needed dosage, as with quercetin + dasatinib. If quercetin were to work synergistically as it does with dasatinib, then the dose needed with azithromycin might be far lower. Dasatinib (which has a .14 bioavailability in mice) is typically dosed in humans at 100 mg/day for leukemia, while the mouse concentration of 500 nM in the quercetin + dasatinib study would correspond to a human dasatinib dose of about .1 mg — a thousand times less than the dose for cancer. Thus dasatinib, though very expensive for cancer treatment ($300 for a 100 mg tablet), is reasonable when used at such low doses.

 

 

Edited by Turnbuckle, 03 December 2018 - 01:09 PM.

[OP2040]

I am interested in this because even if it is hyped or untranslatable, it potentially kills two birds with one stone.  Persistent microbial load is a huge cause of disease and probably contributor to aging as well.  Of course, we know that the real cause if the collapse of the immune system and the other hallmarks of aging.  But antibiotics and antivirals are an engineered solution to a very serious aging problem.  Until we can regrow a thymus or reboot the immune system, it is well worth it to try to clear microbial infections in a scientific way.  A sampling of what we have learned in recent medical history:

 

1. Herpes virus contributes to Alzheimer's, with potentially up to a ~50% reduction if we had a vaccine for it.  Even though herpes is notoriously hard to clear completely, it's been shown

     that knocking it back to lower levels is very helpful for prevention.

2. HPV is the direct cause of more than 95% of Ovarian cancers, and a large cause of some others as well.  Gardisil has the potential to almost cure ovarian cancer

3. We've always known that periodontal disease is correlated with other diseases, and assuredly because it is a persistent infection.

4. h pylori and stomach cancer

5. Hepatitis and liver cancer

 

Need I go on?

 

The immune system has always been the wild card when it comes to anti-aging.  We're sure it's very important, but not quite sure how to classify it among the other hallmarks.  Clearing senescent cells and bacterial infections at the same time very cheaply can't be anything but a good thing. 

 

There is the question of microbial resistance, not sure how that fits in here....

 

This type of intervention may not cure aging, but it could have a huge impact on the burden of disease at a relatively cheap price. 

[Turnbuckle]

 Dasatinib (which has a .14 bioavailability in mice) is typically dosed in humans at 100 mg/day for leukemia, while the mouse concentration of 500 nM in the quercetin + dasatinib study would correspond to a human dasatinib dose of about .1 mg — a thousand times less than the dose for cancer. Thus dasatinib, though very expensive for cancer treatment ($300 for a 100 mg tablet), is reasonable when used at such low doses.

 

Sorry, I made a mistake above. That actually comes out at .1 grams of dasatinib, not .1 mg, so that would be wildly out of range of anyone's pocketbook.

Edited by Turnbuckle, 03 December 2018 - 02:28 PM.

[Krell]

I just purchase 3 tablets Azithromycin 500 mg for 4 euros here in Spain.  I understand it is cheaper in US.  One suggestion:  Tell your Doctor that your traveling overseas to Mexico, etc., and would like an antibiotic just in case.  Should work to get Rx.    Used here for travel diarrhea. 

 

So what is the single dose that you would suggest in that the recommendation is for 1 low dose as set forth here?       

 

https://medicalxpres...PmfNKq7VyBWp6xw

 

Of course, I would like to make sure that I get the proper concentration without over doing it.  My plan is to take a strong enough dose once a month to clear out the Senolytic cells, and do it again once they have build up again. (How long does it take to repopulate?)  Could be any time frame.  Anyone got any knowledge on this?  Half-life is a long 67 hours, will stay in system for almost 7 days.

 

I can understand everyone's reluctance to use this because of killing the gut bacteria, but when your a healthy 72 yo, but dying slowly this is a big deal.  Senolytic's is probably the number one or two reason we age.  This is a very big deal.  No one has found a drug that would clear out the zombie cells without harming the good one's,

 

Would only recommend this for someone over 60 yo who don't have much to lose.  Younger people don't need it for ageing.

 

Anyone wanting Azithromycin could contact dropshipmd.com in India.  They supply me with Rapamycin and have been very happy.  Had no problem getting it from them when I was in US.

 

I looked at the dropship.com web page but did not find Azithromycin listed.  So I emailed them and got the following reply:

 

Hi dear, we can offer you Azicip 0.45$ per pill x 200 pills, it's minimum order. Registered airmail shipping (not traceable) cost 10$ extra per 300 pills. Ems express shipping (traceable) cost 25$ per 300 pills.

We can accept payments through:

 

1) WIRE transfer to India - we need full billing address of payer and we will prepare proforma invoice;

 

2) Western union - cheaper & faster than WIRE, but money should be sent to our financial partners based in Philippines, because we have shortage of recipients in India;

 

3) Bitcoin

 

If you will have any questions we are happy to assist you. 

Please specify quantity.

 

Regards,

Soni Jain

From:   "Med Impex" <trademedimpex@gmail.com> Date:   Mon, December 3, 2018 10:24 am        

[smithx]

This seems correct based on the data given:

 

Azithromycin molecular weight: 748.984 g/mol

100 u/M concentration: 0.0748984 g/Liter

37% of a 500mg dosage was absorbed.

 

That gives the figures below.

 

One thing to consider: just because 37% of a 500mg dose is absorbed doesn't mean that 37% of a 3gm dose would be absorbed. There may be a limit to absorption of some quantity in some time period. Without more data we can't know for sure.

 

This would suggest IV dosing (if indeed this is at all advisable given the potential cardiac side effects).

 

I personally am going to try it as a face cream first and see if there are any noticeable effects.

 

 

 

Azithromycin and Roxithromycin define a new family of “senolytic” drugs that target senescent human fibroblasts, 2018

 

Fig. 5 captions says

Azithromyin had a potent and selective effect on MRC-5, as it eliminated ~50% of senescent cells without affecting control cells after 5 days, at a concentration of 100 µM. However, Azithromycin had no effect at 50 µM.

 

So I guess we have to convert and compare 100 μM to plasma concentrations of azithromycin, which the French study bellow says is 0.35-0.45 mg/l (following a single oral 500 mg dose).

 

 

I plugged in the numbers into this calculator and the mass it gave, 374.495 mg. The numbers I used:

• molecular weight  = 748.996 g/mol
• 5L or volume, which, google says, is volume of plasma in a 70kg human
• and concentration is what we want, 100 micromolar

 

Then we have to consider the Clinical pharmacokinetics of azithromycin:

 

The bioavailability of azithromycin is approximately 37%. Concomitant administration of oral azithromycin with food significantly decreases by 50% drug bioavailability. Following a single oral 500 mg dose, peak plasma concentrations of about 0.35-0.45 mg/l are attained within approximately 2 hours. With a 500 mg oral dose on day 1, followed by 250 mg daily on days 2 to 5, peak and through plasma concentrations on day 5 are around 0.25 and 0.05 mg/l respectively. These low plasma concentrations are the consequence of extensive and rapid distribution from plasma to tissues. Plasma protein binding is low, less than 50% at plasma concentrations obtained with the usual dosage regimen. Apparent volume of distribution is very large, 25 to 35 l/kg. Azithromycin is mainly eliminated unchanged in the faeces via biliary excretion and transintestinal secretion. Urinary excretion is a minor elimination route: about 6% and an oral dose and 12% of an intravenous dose are recovered unchanged in urine. The mean terminal elimination half-life of azithromycin is 2 to 4 days. The pharmacokinetics of azithromycin is not significantly altered in elderly subjects and in patients with mild to moderate renal or hepatic insufficiency.

 

And not to forget Life-threatening bradyarrhythmia after massive azithromycin overdose, though this was in an infant:

 

9-month-old infant was inadvertently administered azithromycin 50 mg/kg, taken from floor stock, instead of the prescribed ceftriaxone. Shortly thereafter, she became unresponsive and pulseless. The initial heart rhythm observed when cardiopulmonary resuscitation was started was a widecomplex bradycardia, with a prolonged rate-corrected QT interval and complete heart block. The baby was resuscitated with epinephrine and atropine, but she suffered severe anoxic encephalopathy. Torsade de pointes and QT-interval prolongation have been reported after administration of macrolide antibiotics, including azithromycin, both intravenously and orally. This has occurred especially in the context of coadministered drugs that inhibit the cytochrome P450 (CYP) 3A4 isoenzyme, such as ketoconazole and astemizole. However, bradycardia with complete heart block has not, to our knowledge, been reported specifically with intravenous administration of azithromycin alone, either with therapeutic doses or overdose. Clinicians should be alerted about the potential of azithromycin to cause life-threatening bradycardia, and pharmacy systems should be implemented to ensure special care in the safe administration of this drug, especially when dispensed from a point-of-care source

 

[smithx]

Azithromycin certainly doesn't kill all or even most bacteria and certainly won't have any effect on 1 or 2 because they are viral.

 

 

1. Herpes virus contributes to Alzheimer's, with potentially up to a ~50% reduction if we had a vaccine for it.  Even though herpes is notoriously hard to clear completely, it's been shown

     that knocking it back to lower levels is very helpful for prevention.

2. HPV is the direct cause of more than 95% of Ovarian cancers, and a large cause of some others as well.  Gardisil has the potential to almost cure ovarian cancer

 

 

 

Edited by smithx, 03 December 2018 - 05:07 PM.

[OP2040]

Azithromycin certainly doesn't kill all or even most bacteria and certainly won't have any effect on 1 or 2 because they are viral.

 

I certainly didn't intend to imply that it did.  Rather just that antibiotics and antivirals as a class can be powerful agents against aging.  Vaccines are the way to go once we know exactly which microbe does what, as in the case of ovarian cancer.  But most people are too old to benefit from a traditional vaccine since some of these relevant microbes have a >90% infection rate by adulthood.  Nevertheless, the point we are at now, knocking back bacterial and/or viral load is a good thing to the extent that it can be done, and in the future we can have a much more targeted and pervasive approach.

 

Azithromycin is one of the most broad-based antibiotics, so actually it should knock back bacterial load quite a bit in terms of number of types of bacteria.  Naturally, one should try to rebalance with healthy gut bacteria after use.  Although very broadly acting, it is not particularly powerful so that is a drawback.

 

It always has to be stated that everything we do here is temporary and that informs a lot of my strategy.  No current biotech can tackle this issue effectively.  But decreasing microbial load is a great temporary strategy, and proven in many studies as a preventative for almost any disease you can name.  Our goal should be 20-30 years of good, proactive, preventative health, where one doesn't get the diseases that damage tissue to a point of no return.  At that point I'm convinced the tech will be so good that many of the conversations we're having now are going to look trivial.  For example, what will be the point of all this nonsense when we have in targeted in vivo reprogramming? It will just be interesting history.

Edited by OP2040, 03 December 2018 - 06:33 PM.

[Mind]

I know this has been mentioned earlier in the thread, but this bears repeating:

 

THIS WAS AN IN VITRO EXPERIMENT!!

 

Personally I would never considering basing any of my health or rejuvenation efforts on an in vitro experiment.

[QuestforLife]

https://www.ncbi.nlm...pubmed/11867823
 
 

Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial.
Abstract
BACKGROUND:
Relentless chronic pulmonary inflammation is the major contributor to morbidity and mortality in patients with cystic fibrosis (CF). While immunomodulating therapies such as prednisolone and ibuprofen may be beneficial, their use is limited by side effects. Macrolides have immunomodulatory properties and long term use dramatically improves prognosis in diffuse panbronchiolitis, a condition with features in common with the lung disease of CF.
METHODS:
To determine if azithromycin (AZM) improves clinical parameters and reduces inflammation in patients with CF, a 3 month prospective randomised double blind, placebo controlled study of AZM (250 mg/day) was undertaken in adults with CF. Monthly assessment included lung function, weight, and quality of life (QOL). Blood and sputum collection assessed systemic inflammation and changes in bacterial flora. Respiratory exacerbations were treated according to the policy of the CF Unit.
RESULTS:
Sixty patients were recruited (29 men) of mean (SD) age 27.9 (6.5) years and initial forced expiratory volume in 1 second (FEV1) 56.6 (22.3)% predicted. FEV1% and forced vital capacity (FVC)% predicted were maintained in the AZM group while in the placebo group there was a mean (SE) decline of -3.62 (1.78)% (p=0.047) and -5.73 (1.66)% (p=0.001), respectively. Fewer courses of intravenous antibiotics were used in patients on AZM (0.37 v 1.13, p=0.016). Median C reactive protein (CRP) levels declined in the AZM group from 10 to 5.4 mg/ml but remained constant in the placebo group (p<0.001). QOL improved over time in patients on AZM and remained unchanged in those on placebo (p=0.035).
CONCLUSION:
AZM in adults with CF significantly improved QOL, reduced CRP levels and the number of respiratory exacerbations, and reduced the rate of decline in lung function. Long term AZM may have a significant impact on morbidity and mortality in patients with CF. Further studies are required to define frequency of dosing and duration of benefit.

 
Azithromycin doses used commonly
https://reference.me...hromycin-342523
 
 
 

Acute Bacterial Exacerbations of Chronic Obstructive Pulmonary Disease
500 mg PO once, then 250 mg once daily for 4 days
Alternatively, 500 mg PO qDay for 3 days
Acute Otitis Media
500 mg PO once, then 250 mg once daily for 4 days
Genital Ulcer Disease (Chancroid)
1 g PO once
Acute Bacterial Sinusitis
500 mg/day PO for 3 days or 2 g PO once

 
Looks to me like this drug has been well tested for safety at similar dosages to that we might use for senolytics.

Edited by QuestforLife, 06 December 2018 - 01:11 PM.

[xEva]

 
Looks to me like this drug has been well tested for safety at similar dosages to that we might use for senolytics.

 

what dosages you have in mind?

[PAMPAGUY]

I have just completed my second round of Azithromycin.  First round was 1500 mg. orally once.  Wait 1 week.  Second round 500 mg x 5 days. The inVitro experiment was for 5 days at a low dose.  Will wait 1 month and do again.  No side effects that I could tell.  Taking Dr. Mercola probiotics to repopulate my gut after each regiment. 

 

While this was an inVitro trial, I would like to emphasis that this antibiotic has been used for years and extended the lives of cystic fibrosis patients for years.  As stated in https://medicalxpres...fNKq7VyBWp6xw, 

 

"Originally, the thinking was that Azithromycin is killing harmful bacteria in cystic fibrosis patients – but our tests now shed a new light on what might be actually going on.

 

"Our new interpretation is that the antibiotic is probably eliminating the "inflammatory" fibroblasts, in other words, the senescent cells that are normally associated with ageing.    

Also,

"At a single low-dosage, Azithromycin was shown to effectively kill and eliminate the senescent cells, with an efficiency of 97 percent.

Moreover, the normal healthy cells thrived in the presence of Azithromycin."    https://www.aging-us...cle/101633/text

Show me one single senescent cell treatment that has these results including the hype on Fisetin and I will switch.

 

[Mind]

I have just completed my second round of Azithromycin.  First round was 1500 mg. orally once.  Wait 1 week.  Second round 500 mg x 5 days. The inVitro experiment was for 5 days at a low dose.  Will wait 1 month and do again.  No side effects that I could tell.  Taking Dr. Mercola probiotics to repopulate my gut after each regiment. 

 

While this was an inVitro trial, I would like to emphasis that this antibiotic has been used for years and extended the lives of cystic fibrosis patients for years.  As stated in https://medicalxpres...fNKq7VyBWp6xw, 

 

"Originally, the thinking was that Azithromycin is killing harmful bacteria in cystic fibrosis patients – but our tests now shed a new light on what might be actually going on.

 

"Our new interpretation is that the antibiotic is probably eliminating the "inflammatory" fibroblasts, in other words, the senescent cells that are normally associated with ageing.    

Also,

"At a single low-dosage, Azithromycin was shown to effectively kill and eliminate the senescent cells, with an efficiency of 97 percent.

Moreover, the normal healthy cells thrived in the presence of Azithromycin."    https://www.aging-us...cle/101633/text

Show me one single senescent cell treatment that has these results including the hype on Fisetin and I will switch.

 

"If we consider our results and then we also consider what results have been achieved in clinical trials with cystic fibrosis patients, we are probably looking at the same mechanism(s), whereby antibiotics are removing inflammatory senescent cells and boosting healthy ones.

 

 

The mechanism by which cystic fibrosis patients show improvement with the use of Azithromycin, is currently unknown, as far as I am aware. At this point it is only speculation that the improvement comes through senolytic action (based upon a recent in vitro experiment). It seems like a good theory at this point, but it is unproven.

 

If people are taking Azithromycin to see if they can reduce the burden of senescent cells, they should be testing before and after, otherwise it is just a waste of time and money. For people under 50 and especially under 40, you probably won't notice much difference anyway because you don't have many senescent cells. It would still be nice to remove them, but don't expect huge changes.

[OP2040]

@pampaguy,

great stuff.  I wouldn't necessarily assume that all of the health effect is senolytic.  I'm not sure if the study makes that claim or not.  The fascinating thing here is that bacteria are cells too, which is to point out the obvious.  But the implications are very interesting.  So Az can get rid of bacterial cells alongside senescent cells, but not normal cells.  That is a very juicy piece of scientific evidence that leads to all kinds of interesting questions.  Is there some fundamental similarity between senescent cells and bacterial cells? Is there some interaction between the two?  Do the two types of cells have some mechanisms in common?  Microbial load is a pretty big deal, so then we can ask, are we killing two birds with one stone here? 

 

Take this with a grain of salt because I can't remember where I read it.  I remember something about a claim that the longevity of some Mediterranean populations, particularly Sicilian, may be due to their relative isolation from microbial load after WW2, and not so much to do with their diet.

 

Aside from that potentially illegitimate claim, there is plenty of evidence that microbial load plays a large role in healthspan at least.  Anyway, exciting stuff.

[PAMPAGUY]

99% of antibotics do not work. (Kill the bad and leave the good alone) Az has unique properties that others don't have. See trial.. What is interesting is all the compounds thay do not work listed in the table at the end of the trial