81 replies to this topic

[OP2040]

That is a very controversial statement to make even with your extra explanation, unless I'm misinterpreting what you're saying.  They wouldn't even be called antibiotics if they didn't at least preferentially kill bacteria.  If they didn't preferentially kill bacteria preferentially, then their main effect would be death, not the clearance of an infection.  Clearly 99% of antibiotics DO work for their intended use to some degree or another, aside from cases of resistance. 

 

If you mean 99% don't clear senescent cells, then say that, not that they "don't work".  The point is that Az is special in this respect offering us an opportunity to study a possible commonality between bacteria and senescent cells.  It could be we already know what the mechanism is and this it's rather mundane.  But if we don't, then to know the mechanism here would be extremely valuable scientific fodder...

[PAMPAGUY]

This entire trial was about clearing sensecence cells not bacteria. They tested many compounds including antibiotics and supplements, etc.

https://www.aging-us...cle/101633/text

[OP2040]

This entire trial was about clearing sensecence cells not bacteria. They tested many compounds including antibiotics and supplements, etc.

https://www.aging-us...cle/101633/text

 

The trial doesn't need to be about bacteria to talk about Az being an antibiotic, since we already know it's also an antibiotic. 

 

Antibiotics preferentially kill bacterial cells.......Senolytics preferentially clear senescent cells.....there may be an interesting cellular connection here to follow up on. 

Edited by OP2040, 23 December 2018 - 08:07 PM.

[daver]

     At Inhousepharmacy.vu you can order medicines online.  I've been doing so for many years.  Asthma drugs, antibiotics, etc.  You may fax a prescription to them, but you don't have to.  Before going to checkout  there's a login box:  simply give them your email address and continue on.  I ordered Azithromycin from them last year, after reading "A cure for asthma?" by Dr. David Hahn.  After 12 weeks of Azithromycin, I'm now free of the steroid- dependent asthma that has plagued me for 20 years. 

[Izan]

     At Inhousepharmacy.vu you can order medicines online.  I've been doing so for many years.  Asthma drugs, antibiotics, etc.  You may fax a prescription to them, but you don't have to.  Before going to checkout  there's a login box:  simply give them your email address and continue on.  I ordered Azithromycin from them last year, after reading "A cure for asthma?" by Dr. David Hahn.  After 12 weeks of Azithromycin, I'm now free of the steroid- dependent asthma that has plagued me for 20 years. 

 

 

What dosage?

[daver]

     I took 500 mg on wednesday, thursday and friday the first week and for the next 11 weeks it was 500 mg on thursday and on friday.  

[QuestforLife]

     I took 500 mg on wednesday, thursday and friday the first week and for the next 11 weeks it was 500 mg on thursday and on friday.  

 

Thanks for you contribution. Are you taking azythromycin primarily for asthma or as a senolytic?

 

In 2018 I tried a 1g loading dose and 500mg daily follow ups for 10 days. I felt tired a few hours after the loading dose, but soon recovered, and otherwise felt good.

 

Recently I tried a 2g loading does and 1g daily follow ups for 5 days. On day 2 I felt short of breath, but this passed within a day and I have felt very clear ever since.

 

I am taking this as a senolytic part of a progenitor cell stimulating protocol. I did suffer with asthma as a child however.

[xEva]

 The inVitro experiment was for 5 days at a low dose.  ...
 
...
 
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, 
...

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

 
The last statement by medicalexpress.com does not correspond to the reality described in the original paper. The same goes for your own opening statement, "The inVitro experiment was for 5 days at a low dose."  Not a low dose at all! Translated into in vivo pharmacology, the dose needed is several times higher than the commonly used dose for infection (calculated in the beginning of the thread).  Again, at the half the high dosage they used, there was no noticeable senolytic effects.
 
Which is not to say that it might, after all, show a senolytic effect on humans taking normal  dosages, so I'm all ears about the effects it had on you guys! But please don't wrap it into a semblance of a legitimate scientific reference, coz it's misleading.
 
 

...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?

 

 at usual dosages used, AZ is considered bacteriostatic not bactericidal. It does not kill the bacteria but inhibits their growth by binding "to the 50S subunit of the bacterial ribosome, thus inhibiting translation of mRNA" (google). 50S subunit of the bacterial ribosome is a common target for many antibiotics, the other one is 30S subunit. Both are specific to prokaryotes.

 

Re "fundamental similarity between senescent cells and bacterial cells" there is none, but there is a fundamental difference, and. other than size, it is the difference between eukaryotes and prokaryotes. There is a similarity between the mitochondria and bacteria though, including the structure of their membranes.

Edited by xEva, 29 January 2019 - 08:23 PM.

[QuestforLife]

Re "fundamental similarity between senescent cells and bacterial cells" there is none, but there is a fundamental difference, and. other than size, it is the difference between eukaryotes and prokaryotes. There is a similarity between the mitochondria and bacteria though, including the structure of their membranes.

I don't think we should dismiss the anti bacterial connection, given that the proposed Senolytic mechanism of action of azithromycin is metabolic stress. It is logical that senescent cells would have faulty mitochondria, though we'd need to see more data before we can say for sure that this is how they are being dispatched.

[xEva]

I don't think we should dismiss the anti bacterial connection, given that the proposed Senolytic mechanism of action of azithromycin is metabolic stress. It is logical that senescent cells would have faulty mitochondria, though we'd need to see more data before we can say for sure that this is how they are being dispatched.

 

 

It is well-known that mitochondria are in many ways similar to bacteria -- that's one of the reasons they are suspected to be of bacterial origin. Many antibiotics have adverse effects on mitochondria. This is especially true of antimicrobial peptides which target the negatively charged membranes, which is a feature of both bacteria and mitochondria. This equally applies to the endogenous defensins and contributes to inflammation which can be also destructive to the host tissues, the so called collateral damage of the immune response.

 

was it in this thread or another one on the same topic, where it was already discussed that AZ caused mitochondrial stress which healthy cells were able to overcome? The mitochondrial stress part was mentioned in the paper.

 

My take on this is that AZ caused mitochondrial stress in all cells, but healthy cells were able to overcome it, presumably because they have access to the nucleus, while the senescent cells, presumably, don't

 

I'm more concerned by the apparent proliferation it caused in the healthy cells. According to the graph, (Fig.5 -?) in just a few days, their number increased by a substantial percentage (over 10% -?). I know the medicalexpress.com described this growth spur as "healthy cells thrived" but I'm not sure this was such a good thing.

[QuestforLife]

My take on this is that AZ caused mitochondrial stress in all cells, but healthy cells were able to overcome it, presumably because they have access to the nucleus, while the senescent cells, presumably, don't

 

I'm more concerned by the apparent proliferation it caused in the healthy cells. According to the graph, (Fig.5 -?) in just a few days, their number increased by a substantial percentage (over 10% -?). I know the medicalexpress.com described this growth spur as "healthy cells thrived" but I'm not sure this was such a good thing.

 

I wouldn't be too concerned - the treatment just forced the normal cells' mitochondria to become more efficient, so the cells were then able to reproduce more quickly (in vitro) and more than makeup for the initial hit. I would expect the effect would be analogous in vivo to someone getting fit, and wouldn't necessarily lead to out of control cells. After all elimination of damaged mitochondria should reduce cancer incidence, IMO.

[PAMPAGUY]

What is autophagy?  

• “Auto” means self, and “phagy” means eating
  • It’s the process by which cells eat themselves – the dysfunctional cells (like cancer cells) tend to be “eaten” first
• Almost everybody has cancer cells in their body
  • “The probability that you and I are sitting here without at least one cancer cell in our body is pretty low”
  • But virtually, all the time, your immune system is recognizing cancer cells as “non-self” and terminating them – the time that it doesn’t, is when we develop cancer

Aging = Inflammation  

• If you were to do a biopsy of your leg muscle today, and compare it to a biopsy of your leg muscle 10 years ago, you’d see MUCH more inflammation in the cells
  • You’d see much more cytokines, macrophages, and the chemical signals that inflammatory cells use to speak to each other
  • “Inflammation and aging are so tightly wound together”

What’s mitophogy?  

• When damaged mitochondria are recycled 
• We all have ~20,000 genes in our DNA (which we got from our parents), but mitochondria have their own DNA (37 genes) as well
  • Mitochondrial DNA comes from your mom
  • This mitochondria DNA is bacterial in origin (compared to the DNA in your nucleus, which is of human origin)
• A promising hypothesis – One of the reasons we see an increase in inflammation with aging is that as we age, we get more mitochondrial breakdown, and as more mitochondria are breaking down, perhaps that’s eliciting an immune response
  • (Since the mitochondrial DNA is bacterial in origin, once it gets out of the mitochondria into the cytoplasm, the body thinks of it “non-self”, and attackedn it )

This is from Dr. Attia's podcast attached.  Mitochondial DNA  is bacterial in orgin.  My take is that is why Azithromycin selectively destroys them and leaves healthy alone.  Cystic Fibrosis patients do really well on it.

https://podcastnotes.../01/17/attia-5/

 

[QuestforLife]

What is autophagy?

• “Auto” means self, and “phagy” means eating
  • It’s the process by which cells eat themselves – the dysfunctional cells (like cancer cells) tend to be “eaten” first
• Almost everybody has cancer cells in their body
  • “The probability that you and I are sitting here without at least one cancer cell in our body is pretty low”
  • But virtually, all the time, your immune system is recognizing cancer cells as “non-self” and terminating them – the time that it doesn’t, is when we develop cancer

Aging = Inflammation

• If you were to do a biopsy of your leg muscle today, and compare it to a biopsy of your leg muscle 10 years ago, you’d see MUCH more inflammation in the cells
• You’d see much more cytokines, macrophages, and the chemical signals that inflammatory cells use to speak to each other
• “Inflammation and aging are so tightly wound together”

What’s mitophogy?

• When damaged mitochondria are recycled
• We all have ~20,000 genes in our DNA (which we got from our parents), but mitochondria have their own DNA (37 genes) as well
  • Mitochondrial DNA comes from your mom
  • This mitochondria DNA is bacterial in origin (compared to the DNA in your nucleus, which is of human origin)
• A promising hypothesis – One of the reasons we see an increase in inflammation with aging is that as we age, we get more mitochondrial breakdown, and as more mitochondria are breaking down, perhaps that’s eliciting an immune response
  • (Since the mitochondrial DNA is bacterial in origin, once it gets out of the mitochondria into the cytoplasm, the body thinks of it “non-self”, and attackedn it )

This is from Dr. Attia's podcast attached. Mitochondial DNA is bacterial in orgin. My take is that is why Azithromycin selectively destroys them and leaves healthy alone. Cystic Fibrosis patients do really well on it.
https://podcastnotes.../01/17/attia-5/

One slight modifocation: I expect that apoptosis is required to get mitochondrial fragments in the blood and the immune response. Hence successful mitophapgy should avoid this problem. It's only when some sort of stress is too much for the poor quality mitochondria in some cells that you get a caspase cascade and loss of the cell and mitochondria in the blood. Over many years mitophapgy is indequate (inadequate for MiTo quality control but probably perfectly fine from ATP production point of view) so you get lots of Mito heavy cells. That's my take on it anyway.

[Ovidus]

Some people have already experimented with the Azitromycin I see

Has anyone combined Azitromycin  + Dasatanib + Quercetin?

[Rays]

When taking azithromycin, won't that kill your microbiome? I'd like to keep my Gordonibacter, amongst others.

Are you guys not afraid of losing your valuable microbiome?

 

What can we do to prevent that? Can you take azithromycin sublingually? Is it possible to prevent azithromycin going into the intestines and making sure all is absorbed in the stomach?

 

Is it doable to repopulate your own microbiome, using your own sample?

 

 

[Ovidus]

 

When taking azithromycin, won't that kill your microbiome? I'd like to keep my Gordonibacter, amongst others.

Are you guys not afraid of losing your valuable microbiome?

 

What can we do to prevent that? Can you take azithromycin sublingually? Is it possible to prevent azithromycin going into the intestines and making sure all is absorbed in the stomach?

 

Is it doable to repopulate your own microbiome, using your own sample?

 

 

 has been discussed already

you would inject it and thus bypass the guyt

[Izan]

     I took 500 mg on wednesday, thursday and friday the first week and for the next 11 weeks it was 500 mg on thursday and on friday.  

very interesting, thank you!

[daver]

     Among the nutritional things I take daily is N-Acetyl-Cysteine, 600 mg both at breakfast and lunch (with ample water).  
This might have helped me get rid of the asthma.  Although Dr. Hahn doesn't say it's needed, I think it would be a good idea  for anyone trying to get rid of asthma to include it.

  

" It is NAC’s mucolytic role, in combination with additional influences on oxidative stress that appear to make it useful in persistent, antibiotic-resistant infections. Research demonstrates that NAC can be used in combination with antibiotics or other antimicrobial agents to enhance a pathogenic bacterial colonies’ susceptibility to the effects of such treatments."  https://www.fxmedici...tent-infections

 

A good high potency multi-strain probiotic would, of course, also be a good idea.   I wish there was a way to know if this much Azithromycin has cleared away senescent cells.  I feel the same as I did before.

[Rocket]

I have taken many z-packs as they are nicknamed. I have never felt anything, ever. Period. My wife prescribed herself a z-packs 2 weeks ago. She hasn't reversed aged. You're all barking up the wrong tree. If there are any benefits to this antibiotic, they are outweighed by the negatives of running antibiotics.

[QuestforLife]

I did a bit more thinking about this, and perhaps the 100uM isn't really achievable in vivo. 

 

Yes, you can get those levels in the blood by taking azithromycin at the amounts you would for antibacterial action, but to get it at those levels distributed across all tissues - by my very rough calculations you're talking about a 5g loading dose and then a 3 g maintenance dose for 5 days.

 

I've been unable to find any precedent for this dose, so it'd be a brave person who'd try it! 

[DeltaWave]

Doxycycline, Azithromycin and Vitamin C (DAV): A Potent Combination Therapy for Targeting Mitochondria and Eradicating Cancer Stem Cells (CSCs)

https://pubmed.ncbi....date&from_pos=5

[PAMPAGUY]

Dr. Green has a new website targeting https://senolyticstr...reatment.com/. He points out that there are 4 different types of senolytics. (zombie cells) and there are different treatments which target each one.  He suggests using Fistein 1500 mg x 3 consecutive days x every 3 months for aging purposes. (they are using 20mg/kg in Mayo Clinic trials x 2 consecutive days in elderly patients, as yet unpublished results)  Azithromycin 500 mg x 3 spread over 1 week x every 3 months. (targets fibroblast)    Dasatinib 100 mg x 3 consecutive days x every 3 months. He has set up a compounding pharmacy to make Dasatinib affordable for his patients.  I order powder from China.  He believes that Rapamycin slows down senescence, but cannot remove them.   Please refer to his website for additional info.

 

The following is an interview by Dr. Blagosklonny for his Aging article.

 

Aging, COVID-19 and more   Interview with Alan S. Green, M.D., who practices medicine in New York state, and who, in 2016, began to treat patients with rapamycin (Sirolimus), an anti-aging drug. Interview was taken via email on March 31, 2020, by Editor Dr. Blagosklonny for the journal Aging. Question 1: How many patients and for how long have you treated with rapamycin? Answer 1: Patient number 1 is myself, treated for 4 years. An additional 480 patients treated from 3 years to present. Question 2: Rapamycin (Sirolimus) and its analog Everolimus are FDA-approved drugs used in millions of patients with several severe diseases for many years. Based on a few murine models, some people believe that rapamycin may have unacceptable side effects, even though rapamycin extended the health span and life span of mice in these studies. Have you noticed side effects in your patients? Answer 2: Rapamycin in older persons is very beneficial for the brain, heart, muscle, joints, insulin sensitivity, decreasing visceral fat, and prevention various age-related diseases. Rapamycin is a very potent drug and good results dependent on proper dose and interval. My patients show good results with sirolimus [rapamycin] 2 to 8 mg once a week. Major side effect in that range is decrease in activity innate immune system. To extent chronic inflammation is harmful in aging, this is generally beneficial. The basic researchers I follow are Matt Kaeberlein and Veronica Galvan who have recently shown excellent protection against normative aging in heart (dogs) and brain (rats). I have observed those same beneficial results in older humans. Question 3: Z-pak (Azithromycin) that you prescribed to your patients (just in case of possible bacterial complications) is now considered a promising drug to treat COVID-19. Would you like to comment? Also, it was published in Aging by Sargiacomo et al, that Azithromycin and hydroxychloroquine are senolytics, drugs that selectively kill senescent cells. Answer 3: A natural tension always exists between treating physicians who use standard of "reasonable degree of medical certainty" and government scientists who use standard of "definitive proof" and dismiss anything short of definitive proof as "anecdotal". (Perfect is the enemy of Good). As regards recent paper in Aging by Sargiacomo et al, that was an extraordinary important paper connecting COVID-19, aging, senescent cells and senolytics. In 2017 paper, Blagosklonny noted role of Doxycycline and other antibiotics as anti-aging drugs. Azithromycin looks like major drug in prevention and treatment COVID-19. I use same dose used in Cystic fibrosis study (500 mg 3 times a week) in which Azithromycin appears to be acting as senolytic.