It would make things so much easier for us if this was a default thing to look at. The problem is that drugs that treat certain conditions effectively might decrease lifespan which would make companies hesitant to release the data. It should be a mandatory release, but it should also be noted that sometimes a drug that treats a condition that shortens your life increases the lifespan for that individual if the condition is addressed.
So you would say that people here digging through all of this FDA data wouldn’t be of much use? Nothing to gain from it at all? Looking at rapamycin data for instance I don’t see anything of much use indicating you are correct that carcinogen/toxicology data ≠ lifespan data
Do you have a link to the podcast where you discuss this?
What makes you say this? This doesn’t seem true. Million Molecule Challenge uncovered Omipalisib as something that can increase lifespan in C Elegans. Was this known before? This is one such candidate to compare the carcinogenicity data, though looking it up I think it hasn’t gone through this process yet as it is still in trials.
This is a good starting point. As I said earlier I don’t see anything in the toxicology data from rapamycin indicating lifespan effects. This doesn’t mean we will never find useful data here for other substances.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity:
Carcinogenicity studies were conducted in mice and rats. In an 86-week female mouse study at sirolimus doses 30 to 120 times higher than the 2 mg daily clinical dose (adjusted for body surface area), there was a statistically significant increase in malignant lymphoma at all dose levels compared with controls. In a second mouse study at dosages approximately 3 to 16 times the clinical dose (adjusted for body surface area), hepatocellular adenoma and carcinoma in males were considered sirolimus-related. In the 104-week rat study at dosages equal to or lower than the clinical dose of 2 mg daily (adjusted for body surface area), there were no significant findings.
Genotoxicity:
Sirolimus was not genotoxic in:
- the in vitro bacterial reverse mutation assay
- the Chinese hamster ovary cell chromosomal aberration assay
- the mouse lymphoma cell forward mutation assay
- the in vivo mouse micronucleus assay
Female Fertility (Rat):
When female rats were treated by oral gavage with sirolimus and mated to untreated males, fertility decreased at 0.5 mg/kg (2.5-fold the clinical human dose on a BSA basis) due to decreased implantation. Reduced ovary and uterus weights were also observed. The NOAEL for female rat fertility was 0.1 mg/kg (0.5-fold the clinical human dose).
Male Fertility (Rat):
When male rats were treated by oral gavage with sirolimus and mated to untreated females, fertility decreased at 2 mg/kg (9.7-fold the clinical human dose on a BSA basis). Testicular, epididymal and prostate atrophy, seminiferous tubule degeneration, and reduced sperm counts were observed. The NOAEL for male rat fertility was 0.5 mg/kg (2.5-fold the clinical human dose).
Short-Term IV Study:
Testicular tubular degeneration was also seen in a 4-week intravenous study.
