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Azithromycin: Can this antibiotic treat symptoms of ageing?

azithromycin senolytics

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#1 Engadin

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Posted 11 June 2020 - 01:50 PM


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S O U R C E :   Health Europe

 

 

 

 

 

 

Professor Michael P Lisanti of the University of Salford highlights the potential applications of senolytic drugs in treating age-associated conditions.
 
Professor Michael P Lisanti, Chair in Translational Medicine at the University of Salford, has been an active research scientist for more than 30 years and is an expert in the field of cellular senescence. In 2018 Lisanti, along with his wife and research partner Professor Federica Sotgia, co-authored a paper entitled ‘Azithromycin and Roxithromycin define a new family of “senolytic” drugs that target senescent human fibroblasts’, which identified the FDA-approved antibiotic azithromycin as a senolytic drug: a compound which can be used to treat the symptoms of ageing.
 
Their research was made possible through generous funding contributions from Lunella Biotech, Inc, a Canadian-based pharmaceutical developer which fosters medical innovation; the Foxpoint Foundation, also based in Canada; and the Healthy Life Foundation, a UK charity which funds research into ageing and age-related conditions. Lisanti speaks to HEQ about his work and the future of senescence studies.
 
 
Can you give us a brief introduction to the results of your research into senescence and senolytic drugs?
 
We started out focusing on cancer, but the relationship between cancer and ageing led us to shift our focus towards senescence, the process by which cells chronologically age and go into cell cycle arrest. Senescence leads to chronic inflammation: the cells secrete a lot of inflammatory mediators, which allows the cells to become almost infectious; so then neighbouring normal cells become senescent – it has a kind of cataclysmic effect. As you age – especially as you approach around 50 – you begin to accumulate more senescent cells, which are thought to be the root cause of ageing; this then leads to various ageing-associated diseases, such as heart disease, diabetes, dementia and cancer, the most life threatening conditions in the Western world.
 
The goal, therefore, would be to remove the senescent cells. It is possible to use a genetic trick to remove senescent cells from mice: this causes them to live longer by preventing ageing-associated diseases; but it is not possible to use the same genetic trick for humans. We would therefore need a drug that only kills or removes senescent cells; and that could then potentially lead to rejuvenation, thereby extending the patient’s healthy lifespan.
 
We set up a drug assay using normal, commercially available, human fibroblasts: MRC-5, which comes from the lungs, and BJ-1, which comes from the skin. The idea was to artificially induce ageing, which we did using a compound called BrdU. This compound is a nucleoside: it incorporates into the DNA and that leads to DNA damage; and the DNA damage in turn induces the senescence phenotype. The overarching concept was to create a population of cells artificially that were senescent; and then to compare primary cells that were normal with cells which were senescent, with the goal of identifying drugs which could only selectively kill the senescent cells and not harm the normal cells.
 
We had previously observed positive results in tests on the metabolic effects of antibiotics, so our drug screening identified two drugs called azithromycin and roxithromycin, which constitute a new family of senolytic drugs. They’re both clinically approved drugs – azithromycin has been around longer; and has a strong safety profile – and we looked at other members of the same drug family such as erythromycin, which is the parent compound, but erythromycin has no senolytic activity. The characteristics we were looking for appeared to be relatively restricted to azithromycin, which in our observation was very efficiently killing the senescent cells. As we reported in the paper, it had an efficacy of approximately 97%, meaning that it was able to facilitate the growth of the normal cells, while concurrently selectively killing the senescent cells.
 
 
How did you measure the efficacy of the drugs?
 
We tested the drug on normal and senescent cells which were otherwise identical. The senescent cells underwent apoptosis – programmed cell death – so that led us to the conclusion that the drug selectively kills the senescent cells, while at the same time the normal cells are able to continue to proliferate. That selective effect of removing exclusively the senescent cells is what we were searching for; because in this instance we would want a drug that could potentially be used in humans and which would only kill senescent cells.
 
What would be the next steps in proving the credibility of antibiotics removing inflammatory senescent cells and boosting healthy ones?
Obviously, we would have to do clinical trials going forward, but the first step should be to identify the pharmaceutical application. Given that this drug appears to selectively kill and remove the senescent cells, it could be used potentially to prevent ageing-associated disease; and it could therefore potentially extend the human lifespan, especially in terms of reducing diseases and conditions like diabetes, heart disease, dementia and even cancer.
 
Cystic fibrosis is the most common genetic disease in humans; patients with cystic fibrosis are prone to bacterial lung infections. Researchers started to explore the possibility of using azithromycin preventatively in patients with cystic fibrosis; and they found that, while it didn’t necessarily affect patients’ susceptibility to infection, it did prevent lung fibrosis – where the lungs become stiff and the patient is unable to breathe – and in doing so, extended the patients’ lifespan. These studies were focused on myofibroblasts, which at the time weren’t really seen as senescent; whereas the literature now acknowledges a general consensus that myofibroblasts are indeed senescent cells.

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#2 Targz

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Posted 25 July 2020 - 07:56 AM

If anyone is interested in azithromycin I may have some lying around if you want to pay the shipping fee or are close enough to come pick it up.



#3 jroseland

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Posted 12 February 2021 - 08:13 AM

I would not take an antibiotic as an antiaging hack. I investigated Azithromycin and I think it's usefulness is limited to treating serious infections, the side effects are not worth it otherwise.

 

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