So I’m very interested in all this, particularly a lithium-rapa combo since my studies show the main issue with rapa and cancer is ubiquination mediated by GSK-3 preventing mtor inhibition in cancer.
However, I’m very wary of MEK inhibitors as I started taking dihydromyricetin high dose (2 grams) in January of this year and it seemed to cause profound skin aging effects that are only recently starting to go away.
I took dihydromyricetin years ago and didn’t have these problems.
I’m still wary of lithium until more research.
But all these molecules have long history of supplementation so like with many things - it appears the dose makes the poison.
Do not take trametinib for longevity purposes. I worked on synthetic lethal chemo combinations in cancer at a startup for years. We tested this compound and it is not a good idea. The Erk pathway is very important for most epithelial cells. Stick to low risk acarbose and rapamycin combinations and do not consider trametinib. If you have melanoma or another type of solid tumor type then you could consider trametinib. Just trying to prevent you from causing long term damage.
The problem is most targeted protein kinase inhibitor clinical trials are done in patients that failed first line chemo so this is a drug population that can’t be studied long term since they often have less than a year to live. I expect most long term side effects are not documented. The side effect profile does not look promising for a drug used for longevity purposes. The study of combination longevity effect also observed a significant reduction of fecundity so I hope you do not plan on having children. This is presumably also going to be combined with rapa which is also known to reduce fecundity. So I will restate that MEKi drugs all around are a bad class of drugs to consider for longevity based on my risk reward calculations.
Wow - really good information. Thanks for posting this. Its great to have people here who have some in-depth experience with some of these compounds and biochemistry.
What do you mean by rapa is “also known to reduce fecundity?” A recent study shows that a weekly 5mg rapa administration extends child-bearing age for women by decreasing the aging of their ovaries.
