Azithromycin kill/eliminate 97% senescent cells
I assume we're gonna need to get an rx if we're going to self experiment?
"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.
This is the problem with "cell studies." The authors decided to look at what they called a "low dose" of azithromycin (AZM) on cells. They found that 50 uM did nothing, and they needed 100 uM.
That sounds low, but it's not for serum. The MW of AZM is 749 u so 100 uM is basically 75 mg/L. That's far, far over normal therapeutic serum levels of AZM, which hit Cmax of a few TENTHS of a mg/L on a standard Z-pak dose of 250 mg a day (5 mg/kg a day).
In mice 200 mg/kg AZM results in Cmax concentrations of 15 mg/L, which is only 1/5th of 75 mg/kg. (Girard, et al 2005). If the results scale linearly (no guarantees), it would take a dose of 1 gram/kg AZM to get to the senolytic 75 mg/L in the serum. This would be 50 grams AZM for a 50 kg person, which is 200 standard 250 mg AZM pills. That's a ridiculous amount.
Fortunately, AZM doses in tissues are up to 100 times those in serum (now we're back to 2 pills taken at once, at best), but unfortunately this varies by the tissue. For example in rectal tissues, a 1 g dose of AZM (4 standard pills = about 20 mg/kg) resulted in a mean Cmax of 133 mg/kg concentration in tissue. This is twice the theoretical senolytic concentation.
So a 20 mg/kg dose might be enough for senolytic effects in some other tissues, but we can't simply push the dose of AZM arbitrarily, as it has a cardiac proarrythmic side effect.
In humans, 30 mg/kg (a dose of about 6 pills or 1.5 g at once) is about the limit people have used in 1-dose treatment of STDs and ear infections. That's probably right at the edge of what we are looking for and the cardiac effects limit much exploration of higher doses.
That's probably not coincidence! The cardiac toxicity is probably due to high tissue concentration and inhibition of cardiac mitochrondria-- exactly what is happening in senolytic therapy and anti-cancer-stem cell therapy. We can probably expect that the therapeutic window of all drugs that work this way, is not that large. At doses a few times what kills cancer stem cells and senile cells, we start to get effects on normal cells. If that's in your heart, it's not something you can tolerate for a bit, like "chemo." Instead you might be dead from just momentary problems.Reply