There are several studies showing that repeat BCG protects against multiple types of infections which in itself increases lifespan (as well as increasing lifespan by reducing cancer risk) so that is the low hanging fruit. I posted about how to take it orally which is IMO safest and most convenient.
UTIs are common in older people particularly older women who take daily rapamycin. There are several vaccines\immunotherapy treatments against the most common bacteria that cause utis. Uromune MV140 is the best and is specifically tested on people taking immunosuppressive drugs. The same company is trialling a vaccine against respiratory infections MV130 and it is going well, but it is not approved yet.
I’ve been wondering about that “inhibit MTORC-2” issue and found several references that Rap does not directly inhibit MTORC-2 but does disrupt it in other ways. So I’m a bit confused on this
Rapamycin is an acute inhibitor of mTORC1 but not mTORC2, and kinase inhibitors generally target both mTORC1 and mTORC2. Hence, whilst the role of mTORC1 in aging is relatively well defined – rapamycin is well established to extend the lifespan of mice – the study of mTORC2 function has been limited by a lack of specific mTORC2 inhibitors. This is complicated by the fact that chronic rapamycin treatment disrupts mTORC2 in a cell-type and context specific manner. For example, chronic rapamycin disrupts hepatic mTORC2 in vivo, leading to glucose intolerance and insulin resistance; attributed to mTORC2 as Rictor deletion alone also induces hepatic insulin resistance.
I am not sure anyone has a definitive answer to your question.
My own experience from taking rather high doses for almost 3 years is:
It does seem to delay wound healing, papercuts, etc., but does seem to affect my overall immune system in a positive way. Again, I am 83 and I have caught nothing including Covid in the last three years despite exposure in places that are relatively high risk.
Yes, rapamycin doesn’t inhibit mTORC2 directly. However, chronic rapamycin therapy inhibits mTORC2 indirectly. That’s why it’s important to not take it too frequently in too high doses, or else it will start inhibiting mTORC2 too much and cause side effects like e.g. glucose intolerance and increased lipid levels.
I think you will need better mTOR inhibitors without the side effect. Even at 6 mg/week, I suffer enormous pain from mouth sores most of the time. Last cycle, the sores lasted a full two painful weeks. Can’t imagine a higher dose.
Thanks for the reply. I wonder why it affects on some people. My sister and my nephew never had mouth sores from taking rapamycin at 6 mg/wk while it is a completely different situation with me. I have head experts talk about it, but no one has given a good explanation why it is happening. If one knew the biochemical mechanism, then one can try to devise a strategy to prevent it. Don’t want to be condemned to not enjoying the potential benefits of consuming rapamycin due to side-effects
He makes an excellent point. How are the marmosets dying? Diabetes or blood sugar related diseases? If so, adding Metformin or Acarbose or an SGLT2I would probably increase lifespan from 15% to 20-25%!