Azithromycin might have interesting anti-aging effects. It targets senescent cells very effectively and without targeting healthy cells. The effect is concentration dependant though .

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

"Azithromycin, at 100 μM, had no effect on the viability of normal MRC-5 lung fibroblasts, but selectively killed only senescent MCR-5 fibroblasts."

"Neither drug showed any significant effects on viability at 50 μM, indicating that the effects we observed were concentration-dependent."

https://pmc.ncbi.nlm.nih.gov/articles/PMC6286845/

Another macrolide antibiotic Azithromycin also inhibits mTOR according to these studies:

https://pubmed.ncbi.nlm.nih.gov/34600916/
https://pubmed.ncbi.nlm.nih.gov/37633240/
https://pubmed.ncbi.nlm.nih.gov/30334401/

Although there is one study that said it didn't have an effect on mTOR:

https://pubmed.ncbi.nlm.nih.gov/39284999/e

In light of this thread, the findings of this old thread by haidut are even more interesting.

https://lowtoxinforum.com/threads/gut-bacteria-overgrowth-drives-cocaine-addiction-glycine-can-reverse-it.48285/

@yerrag
Yes, although this study shows rapamycin has thymus weight lowering effect in mice. Although there was clearly a dose dependant effect and the HEDs were like 15-60mg per day which is really high, so I'm not sure if there would be any such effect if you were to take just 1-5mg / week .
So the weekly dose of this study was about 30-100 times higher than what most humans take.

https://pmc.ncbi.nlm.nih.gov/articles/PMC9360838/

@yerrag definitely. I think it has benefits because of endotoxin reduction and reduction of toxic chemicals.
But the mTOR activation and high amounts of methionine and cysteine are definitely an issue.
Large amounts of gelatin might protect to some degree. But the studies on rapamycin and methionine restriction are so obvious and many that I don't think theres a way around this.
It always leads back to a high carb diet.

@Lejeboca said in Strong Sistas finally posted an interview with Dr. Ray Peat - The Basics Of Pro-Metabolic:

@yerrag said in Strong Sistas finally posted an interview with Dr. Ray Peat - The Basics Of Pro-Metabolic:

I've been wondering why in one of his last newsletters Ray would say that when the body is in the process of drawing calcium from the bones, in an osteoclastic process, it cannot be at the same time in a full optimal mitochondrial respiratory mode where among other things CO2 is being produced.

From this paper Calcium paradox disease: Calcium deficiency prompting secondary hyperparathyroidism and cellular calcium overload
in Page 7:

Mitochondria are conspicuously affected by
Ca overload [151]. These organelles have the capacity
to store significant amounts of Ca in the form of biologi-
cally inactive amorphous calcium phosphate, but when
their buffer capacity is overtaxed mitochondrian physi-
ology is disrupted with severe reduction of oxidative
phosphorylation, resulting in an ATP deficit that in turn
diminishes the effectiveness of the Ca pump with fur-
ther cellular Ca overload. Elevation of [Ca] stimulates
Ca-activated neutral protease [7,8] and phospholipases
[6], affecting the pathophysiological process of muscu-
lar dystrophy [152] and other diseases characterized by
cellular Ca dishomeostasis [146]

That sounds like a good answer to yerrags question above. We don't want intra-cellular calcium.

@Epik this guy gives a great answer at 51:22

Rapamycin dampens excessive sterile inflammation that is often present unnecessarily in old age.

While cortisol has a strong short term anti-inflammatory effect as well, it is disastrous for the body in the long run.

https://youtu.be/_vsNw-OCciU?si=0N8V-Bdlhelu7iUo

Rapamycin, fisetin and other anti-aging compounds (but not Metformin) help with stem cell formation .

https://pubmed.ncbi.nlm.nih.gov/21615676/

It increases dopamine .

"MPTP-induced reduction of dopamine contents in the striatum and hippocampal CA1 region was improved by nobiletin administration (50mg/kg i.p.). Acute intraperitoneal administration of nobiletin also enhanced dopamine release in striatum and hippocampal CA1,..."

https://pubmed.ncbi.nlm.nih.gov/24316474/

NOB could restore memory impairment via the improvement of neurogenesis by ameliorating neuroinflammation in the hippocampushttps:

//pmc.ncbi.nlm.nih.gov/articles/PMC10181043/

Nobiletin increases testosterone and lowers estrogen.

In this in vitro study nobiletin increases testosterone:

"Furthermore, we found that these compounds enhanced testosterone production via cyclic AMP (cAMP)/cAMP response element binding protein signalling. In particular, the compounds inhibited activation of phosphodiesterase and thereby increased production of cAMP. These findings support the possibility that K. parviflora extract, 5,7-dimethoxyflavone, and nobiletin may mitigate age-related disease and hypogonadism by enhancing testosterone production."

https://www.researchgate.net/publication/306926144_Effect_of_Kaempferia_parviflora_extract_and_its_polymethoxyflavonoid_components_on_testosterone_production_in_mouse_testis-derived_tumour_cells

Nobiletin lowers estrogen by inhibiting aromatase.
https://pubmed.ncbi.nlm.nih.gov/28177754/