81 replies to this topic

[reason]

Researchers here report on two new senolytic compounds identified in the existing library of approved drugs, based on screening work in cell cultures. It is worth bearing in mind that drug candidates that demonstrate good results in cell culture quite often fail to show promise when tested in animals, so it is wise to be patient as new senolytics work their way through the research and development pipeline. There will be a lot more of this sort of thing in the years ahead, as ever greater amounts of funding pour into finding new ways to selectively destroy senescent cells. Any senolytic approach that removes a significant fraction of these cells will produce a degree of rejuvenation in older patients, and so the hunt for mechanisms has taken on something of the air of a gold rush. So far at least four different mechanisms for prompting the self-destruction of senescent cells are targeted by a dozen or more drug candidates, while immunotherapy and suicide gene therapy approaches also exist. This will be a very busy industry a few years from now, and that bodes well for the future of our health and longevity.

Senescence is a clear hallmark of normal chronological aging. Senescence involves potentially irreversible cell cycle arrest, via the induction of CDK-inhibitors, such as p16-INK4A, p19-ARF, p21-WAF and p27-KIP1, as well as the onset of the SASP (senescence-associated secretory phenotype), and the induction of key lysosomal enzymes (e.g., Beta-Galactosidase) and Lipofuscin, an established aging-pigment. Interestingly, SASP results in the secretion of a wide array of inflammatory cytokines, such as IL-1-beta and IL-6, allowing senescent cells to "contagiously" spread the senescence phenotype from one cell type to another, systemically throughout the body, via chronic inflammation. Such chronic inflammation can also promote the onset of cancer, as well as drive tumor recurrence and metastasis.

Using the promoter of p16-IN4KA as a transgenic probe to detect and mark senescent cells, several research groups have now created murine models of aging in which senescent cells can be genetically eliminated in a real-time temporal fashion. Although this cannot be used as an anti-aging therapy, it can give us an indication whether the removal of senescent cells can potentially have therapeutic benefits to the organism. Results to date show great promise, indicating that the genetic removal of senescent cells can indeed prolong healthspan and lifespan.

As a consequence of this exciting genetic data, a large number of pharmaceutical companies are now actively engaged in the discovery of "senolytic" drugs that can target senescent cells. However, we believe that many FDA-approved drugs may also possess senolytic activity and this would dramatically accelerate the clinical use of these senolytic drugs in any anti-aging drug trials. Here, we have used controlled DNA-damage as a tool to induce senescence in human fibroblasts, which then can be employed as an efficient platform for drug screening.

Using this approach, we now report the identification of two macrolide antibiotics of the Erythromycin family, specifically Azithromycin and Roxithromycin, as new clinically-approved senolytic drugs. In direct support of the high specificity of these complex interactions, the parent macrolide compound - Erythromycin itself - has no senolytic activity in our assay system. Interestingly, Azithromycin is used clinically to chronically treat patients with cystic fibrosis, a genetic disease of the chloride-transporter, that generates a hyper-inflammatory state in lung tissue. Azithromycin extends patient lifespan by acting as an anti-inflammatory drug that prevents the onset of lung fibrosis by targeting and somehow eliminating "pro-inflammatory" lung fibroblasts. Therefore, the efficacy of Azithromycin in cystic fibrosis patients provides supporting clinical evidence for our current findings, as these lung fibroblasts are pro-inflammatory most likely because they are senescent.

Link: https://doi.org/10.18632/aging.101633

View the full article at FightAging

[Nate-2004]

Somewhat off topic but interesting.

 

Azithromycin and Roxithromycin define a new family of "senolytic" drugs that target senescent human fibroblasts.

 

"Azithromycin preferentially targets senescent cells, removing approximately 97% of them with great efficiency. This represents a near 25-fold reduction in senescent cells."

 

Unlikely, both of these antibiotics were produced in the 1980's. The first one is the most prescribed antibiotic in the US while the second is only available down under and in Israel. I find it highly improbable that a drug being used by outpatients for decades have had 97% of their SASP producing senescent cells destroyed. We would have already seen a major correlation by now with mortality and longevity outcomes.

 

In 2010, azithromycin was the most prescribed antibiotic for outpatients in the US,^[30]

 

Roxithromycin is available in Australia, Israel and New Zealand

 

Fisetin has more of a chance of being senolytic than either of these drugs do. At least with Fisetin, it hasn't gone through a trial to test its effectiveness while these two drugs, especially the first, has seen four decades of human testing.

Edited by Nate-2004, 17 November 2018 - 09:34 PM.

[smithx]

Very interesting! Thanks for the reference.

 

If nothing else, this could be great as a skin cream or serum (and that might be a relatively safe first test of it).

 

If we were discussing a skin cream, the concentration they said worked was 100 µM, which is the very tiny amount of 0.075 g / L, but that was in tissue culture. A skin cream or serum would likely need a higher concentration to get through the outer layers of skin. There is probably a rule of thumb for this, but I don't know what it is.

 

Somewhat off topic but interesting.

 

Azithromycin and Roxithromycin define a new family of "senolytic" drugs that target senescent human fibroblasts.

 

"Azithromycin preferentially targets senescent cells, removing approximately 97% of them with great efficiency. This represents a near 25-fold reduction in senescent cells."

 

Edited by smithx, 18 November 2018 - 07:04 AM.

[ryukenden]

Any one trying Azithromycin and Roxithromycin as senolytic?

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

https://www.ncbi.nlm...pubmed/30428454

I have been taking Azithromycin as antibiotics from time to time.

I saw a comment from someone taking it regularly for years and he believed ithat t had slowed the ageing. The comment is at the following link (number 2 comment).

https://www.fightagi...lytic/#comments

If one takes it regularly, it can cause some antibiotic resistance and I will be concerned to take it on regular basis. May be once every few months might be an option.

There are few studies using Azithromycin in cystic fibrosis and it appears having positive effects on the condition.

Edited by ryukenden, 18 November 2018 - 09:10 AM.

[Alpharius]

I wouldn`t dismiss Azithromycin too fast. Its interesting that it seems helpful with COPD and lung fibrosis, where senolytics seem to help with lung fibrosis. Coincidence?

Also its interesting that it helps to reduce tissue damage after radiation injury, similar what we have seen with Navitoclax. 

 

The limitation I see here, its in vitro, its only on sensecence induced fibroblasts, while we can see that Fisetin has prolonged lifespan in mice and hit different tissue types.

 

 

 

Cellular senescence mediates fibrotic pulmonary disease.

Schafer MJ, White TA, Iijima K, Haak AJ, Ligresti G, Atkinson EJ, Oberg AL, Birch J, Salmonowicz H, Zhu Y, Mazula DL, Brooks RW, Fuhrmann-Stroissnigg H, Pirtskhalava T, Prakash YS, Tchkonia T, Robbins PD, Aubry MC, Passos JF, Kirkland JL, Tschumperlin DJ, Kita H, LeBrasseur NK.

Nat Commun. 2017 Feb 23;8:14532. doi: 10.1038/ncomms14532.

PMID:  28230051

The Potential Impact of Azithromycin in Idiopathic Pulmonary Fibrosis.

Macaluso C, Furcada JM, Alzaher O, Chaube R, Chua F, Wells AU, Maher TM, George PM, Renzoni EA, Molyneaux PL.

Eur Respir J. 2018 Nov 15. pii: 1800628. doi: 10.1183/13993003.00628-2018. [Epub ahead of print] No abstract available.

 

Azithromycin attenuates acute radiation-induced lung injury in mice.

Tang F, Li R, Xue J, Lan J, Xu H, Liu Y, Zhou L, Lu Y.

Oncol Lett. 2017 Nov;14(5):5211-5220. doi: 10.3892/ol.2017.6813. Epub 2017 Aug 24.

 

Edited by Alpharius, 18 November 2018 - 08:48 AM.

[Turnbuckle]

Unlikely, both of these antibiotics were produced in the 1980's. The first one is the most prescribed antibiotic in the US while the second is only available down under and in Israel. I find it highly improbable that a drug being used by outpatients for decades have had 97% of their SASP producing senescent cells destroyed. We would have already seen a major correlation by now with mortality and longevity outcomes.

 

 

 

Interesting find. I'm not sure the last statement holds, as most people take this for just a few days. Long term users have chronic diseases like COPD, and any increase in longevity would be attributed to other effects. One group did study health effects of azithromycin in COPD patients--

 

Relationship of Absolute Telomere Length

With Quality of Life, Exacerbations, and

Mortality in COPD

 

COPD is an age-related disease. The role of cellular senescence in COPD has

not been fully elucidated. This study examined the relationship between telomere length of

peripheral blood leukocytes and clinical outcomes, including health status, rate of exacerbations,

and risk of mortality in individuals with COPD.

https://sci-hub.se/1...est.2018.05.022

 

 

 

What they found was rather amazing, yet they brushed over it. Mortality in COPD patients who were given a placebo showed a definite relationship to telomere length over the 4 year study. Those with short telomeres died at about four times the rate of those with long telomeres. But in those given azithromycin, this was reversed. Those with long telomeres died at about twice the rate of those with short telomeres. And it appears from Figure 3 that the overall death rate over that period was higher in the azithromycin group.

Edited by Turnbuckle, 18 November 2018 - 10:40 AM.

[extendcel]

It seems azithromycin has immunomodulatory properties, but disrupting gut flora cannot be good for longevity. One has to consider this in experiments with chronic dosages.

[Nate-2004]

 

And it appears from Figure 3 that the overall death rate over that period was higher in the azithromycin group.

 

 

That sounds bad though...

[QuestforLife]

Interesting find. I'm not sure the last statement holds, as most people take this for just a few days. Long term users have chronic diseases like COPD, and any increase in longevity would be attributed to other effects. One group did study health effects of azithromycin in COPD patients--




What they found was rather amazing, yet they brushed over it. Mortality in COPD patients who were given a placebo showed a definite relationship to telomere length over the 4 year study. Those with short telomeres died at about four times the rate of those with long telomeres. But in those given azithromycin, this was reversed. Those with long telomeres died at about twice the rate of those with short telomeres. And it appears from Figure 3 that the overall death rate over that period was higher in the azithromycin group.

Sounds to me like the azithromycin is harmful to all cells to some extent, but in those with many pre existing senescent cells the net effect of their elimination is an overall improvement, but in those with less senescent cells as a proportion of the whole, treatment is harmful (as it damages functional cells).

Basic conclusion, the older you are the more risky you can be. The more selective and safe the treatment the younger age that you should consider it.

[Turnbuckle]

Sounds to me like the azithromycin is harmful to all cells to some extent, but in those with many pre existing senescent cells the net effect of their elimination is an overall improvement, but in those with less senescent cells as a proportion of the whole, treatment is harmful (as it damages functional cells).

Basic conclusion, the older you are the more risky you can be. The more selective and safe the treatment the younger age that you should consider it.

 

 

It’s possible that long telomeres in the azithromycin treated group reflect the efficient removal of senescent cells as well as the still metabolically active cells with senescence-associated secretory phenotypes, thus they would have lost more cells and function than the group with shorter telomeres after azithromycin treatment. If there were sufficient stem cells to replace these cells, then the outcome would be far better for both groups, but particularly for the long telomere group.

[Ms02138]

Any ideas on what dosage regimen might be needed for this effect? In the study above, it was one-time exposure, albeit to senescent cells in a petri dish. In all the review articles on it extending lifespan in cystic fibrosis and a few other related illnesses, they've kept the patients on it continuously--don't see any of those studies that tried one-time or short term dosing.

[xEva]

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

 

 

 

Edited by xEva, 29 November 2018 - 10:38 PM.

[xEva]

Actually, there are more studies in pubmed on this topic
 
Azithromycin-induced proarrhythmia and cardiovascular death, 2017

CONCLUSIONS:
An emerging body of evidence suggests that azithromycin therapy may prolong the QT interval and, in rare cases, precipitate the potentially fatal arrhythmia torsade de pointes. Patients with additional risk factors for QT prolongation appear to be at highest risk, including women, elderly individuals; those with existing or prior history of cardiovascular disease, QT interval prolongation, hypokalemia, hypomagnesium, or bradycardia; and those using concomitant drugs associated with QT prolongation. For patients without these additional risk factors, azithromycin appears to be relatively safe.

 

Risk Evaluation of Azithromycin-Induced QT Prolongation in Real-World Practice, 2018

CONCLUSIONS:
The risk of QT prolongation was increased when patients, particularly the elderly aged 60-79 years, were exposed to azithromycin. Therefore, clinicians should pay exercise caution using azithromycin or consider using other antibiotics, such as amoxicillin, instead of azithromycin.

 
Is azithromycin treatment associated with prolongation of the Q-Tc interval? 2002

CONCLUSION:
In previously healthy persons, a modest statistically insignificant prolongation of the Q-Tc interval without clinical consequences was observed after completion of a course of 3 g of azithromycin administered over a period of 5 days for solitary erythema migrans.

 

And, as for cystic fibrosis dosage, Cystic Fibrosis Pulmonary Guidelines Chronic Medications for Maintenance of Lung Health, 2007 says:

 

Azithromycin doses ranged from three times weekly at 250 or 500 mg  to 250 mg daily.

 

So it sounds like they did not achieve the senolytic concentration of 100µM in cystic fibrosis patients, which was brought up in another thread.

[xEva]

oops and I forgot the most important part, and that is how 0.4 mg/L compares to 100 µM -- and I can't believe the answer I'm getting. Maybe someone can help?

 

when I convert 0.4 mg/L (which is the average peak plasma concentration after 500mg dose) to µM, I get 0.5340, which is about 187 times lower than the senolytic  concentration of 100 µM -- and if this is right, why would the authors suggest this untenable idea?

 

No one in their right mind will take a dose this big. So I'm hoping I figured it wrong.

 

So, the question is, how much in µM is 0.4 mg/L, when molar mass is 748.996 g/mol ?

Edited by xEva, 30 November 2018 - 12:19 AM.

[HaplogroupW]

 

So, the question is, how much in µM is 0.4 mg/L, when molar mass is 748.996 g/mol ?

 

Yes, using your molecular weight I get 0.4 mg/L = 0.5 micro-molar.

[xEva]

Thanks Haplo

 

Ok then I guess we have to consider the volume of distribution. According to this,

The 70 kg 'standard male' contains 42 liters of water - 60% of his body weight. The hypothetical adult female contains 55% of her body weight as water: this lower percent being due to a higher fat content.

 

which means that we have to only change the number of liters in that calculator above. For a 55kg female like myself that would be 30.5L, for which the molarity calculator gives 2.2844 g, and with 37% availability, it comes to 6 g.

 

A standard 70kg male would need 3.1458g -> 8.5g

 

which is kinda a lot! And to keep concentration this high for 5 days (which is what they did in their in vitro study) is kinda scary (considering all those QT interval pubmed studies above). I personally would wait for human studies.

 

this has been a sorta fun way of killing time

 

 

Edited by xEva, 30 November 2018 - 06:58 AM.

[StanG]

Where can I buy this without a perscription?

[StanG]

Where can I buy Azithromycin without a perscription?

[xEva]

Where can I buy Azithromycin without a perscription?

 

try indian pharmacies.

 

how much are you planning to take?

Are you satisfied with my efforts? I'd prefer someone else contributes at least an opinion -- as the saying goes, one head is good but two is better. 

[PAMPAGUY]

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.

 

https://medicalxpres...PmfNKq7VyBWp6xw

Edited by PAMPAGUY, 01 December 2018 - 11:05 AM.

[sphere]

Antibiotics eliminate senescent cells associated with ageing

.you thoughts appreciated. Almost outrageous results, only >>senescent cells in culture.<< but geez 97% >>Moreover, the normal healthy cells thrived in the presence of Azithromycin.<<

if this holds up in vivo it's a game changer. and messes big time with many companies spending big bucks on getting similar results. Therefore be careful with "expert" opinion as this is threatening to many experts  

Reason; what do you think? Always trust your thoughts as a good starting point:

>>Now, scientists have shown for the first time that an FDA-approved antibiotic – Azithromycin – can effectively target and eliminate senescent cells in culture.

Publishing in the journal Aging (US), a team from the University of Salford's Translational Medicine Laboratories compared the effects of a panel of FDA-approved drugs, on i) normal cells and ii) senescent cells, derived from human skin and lungs.

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.

"It was an astonishing result, and one that got us thinking about the implications for treating or preventing a variety of ageing-associated diseases," said Professor Michael P. Lisanti, the research lead.

"Azithromycin is a relatively mild antibiotic that has been proven to extend lifespan in cystic fibrosis patients by several years.

"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.

"If that is the case, then we may have unearthed a very inexpensive and readily available method of eliminating ageing cells that are toxic to the body."

 

 

https://medicalxpres...PmfNKq7VyBWp6xw

[sphere]

and here's the link to study

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

[QuestforLife]

and here's the link to study
https://www.aging-us...cle/101633/text

Fascinating. If it is working in cystic fibrosis in the way they suggest, then it should also help with pulmonary fibrosis as well and possibly arthritis and other auto immune triggered maladies.

[OP2040]

Thanks Sphere, I've read this with great interest as well.  Problem is, you need a prescription, mild or not.   The only reason I would still favor the Fistein study somewhat is that they targeted many tissues in that study, whereas here they only look at fibroblatsts.  It's not to say that it isn't effective in other cells, but it isn't proven.

 

Does anyone know where you can get this without a prescription?  I'm thinking the biggest advantages may be that  it's not as expensive as Fisetin, and it could help with the many disease processes related to persistent bacterial infection.

 

In the last couple years, we have seen just how powerful the microbes can be in disease, and therefore probably in aging as well.  Of the many studies I could cite, the most intriguing is the Herpesvirus/Alzheimer's connection.

 

Coming back to aging, it begs the question.  Would thymic rejuvenation pretty much solve most of this problem, or is there much more to the microbial burden and aging phenomenon?  A proper thymic rejuvenation study is on my wish list.  I hope when Fahy publishes his study there will be lots of biomarkers, etc.

[Iuvenale]

I bought some at chewy.com. Made for aquarium fish. Between this and the dasatinib, quercetin, piperlongum, fisetin, and tocotrienols I’ve taken, I should be pretty good with respect to senescent cells.

[sphere]

Let's ask now; which of the non-prescription internet pharm's  are reliable that folks here use?

Generic and cheap of Azithromycin is Azee: https://www.practo.c...-mg-tablet-1018

quite cheap; will be easy to get without a prescription  online

 

>> whereas here they only look at fibroblatsts.  It's not to say that it isn't effective in other cells, but it isn't proven.<< Ty for that comment.

Reason replied to an email [very impressed by his quick reply]

>>All of the more effective existing senolytics can be made to kill near all senescent cells in culture. This one just has low off-target effects on cells in culture. That doesn't mean you can just take a very high dose of this safely; you'd have to go look at what else that might do that isn't great, which is probably recorded in the early trials in animals and humans for this compound. For new senolytics, as a general rule it is always worth waiting for the mouse studies, and for an initial understanding of the mechanism of action before getting too excited.<<

 

wise advice I think.

 

I did do a 4 day fast with 5 days of fisetin at 1000mg/day. with olive oil and coconut oil. Bioavailability is an issue and can be improved beyond just the added oils that I took it with. Not expensive, just did swanson's but other expedients with the 100mg's per tablet so not ideal, available from China without added stuff if ui have a trusted source from China.

Effects hard to say as I'm over 70 but no real health issues and did not do tests before/after. No side effects in terms of what I physically felt--quite gentle. 

 

Probably will do again in 6 months [i hate fasting on only water in winter so in spring/summer], 

 

Certainly will keep my eye out for the mouse studies, except who will fund? the financial incentive is not there. In fact the generic Azee is available as an injection. That may eliminate some of the possible negative side effects [antibiotics should generally be avoided imo as they deciminate the "good" gut bacteria, an injection would side-step that]

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

 

again if folks here use a non-prescription online pharm perhaps that is available--the azee oral will be for sure 

 

 

Thanks Sphere, I've read this with great interest as well.  Problem is, you need a prescription, mild or not.   The only reason I would still favor the Fistein study somewhat is that they targeted many tissues in that study, whereas here they only look at fibroblatsts.  It's not to say that it isn't effective in other cells, but it isn't proven.

 

Does anyone know where you can get this without a prescription?  I'm thinking the biggest advantages may be that  it's not as expensive as Fisetin, and it could help with the many disease processes related to persistent bacterial infection.

 

In the last couple years, we have seen just how powerful the microbes can be in disease, and therefore probably in aging as well.  Of the many studies I could cite, the most intriguing is the Herpesvirus/Alzheimer's connection.

 

Coming back to aging, it begs the question.  Would thymic rejuvenation pretty much solve most of this problem, or is there much more to the microbial burden and aging phenomenon?  A proper thymic rejuvenation study is on my wish list.  I hope when Fahy publishes his study there will be lots of biomarkers, etc.

 

[StanG]

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).

 

[StanG]

Hi luvenale,

 

They only sell Azathioprine (is this the same)  and they seem to say you need a vet's approval of some kind. Did you get a vet to write you something?

[stefan_001]

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?

[Iuvenale]

I don’t see it anymore. I’ll remove my post.