Well, I go by the example of CR, which in some ways is a much simpler intervention - it’s just restricting calories to various levels.
Yet it doesn’t extend lifespan for all, and for some it shortens. And yes, there are nuances, like age of initiation, how sudden the onset, compensatory micronutrients etc., but the fact remains it shortens lifespan for some. And for others there seem to be no benefits to CR.
Also, there are drawbacks and side effects, with vulnerabilities, such as pathogens.
Rapamycin seems very similar in many ways. There are some who don’t benefit at all, and others who are actively harmed. It has not been proven to extend lifespan or healthspan in humans. The danger of bacterial infections is very real. There are concerning possible risks of interstitial lung disease and pancreatic beta cell toxicity and more. It is much more complicated than CR to find the right dosing protocol - we have some hints but are very far from any confirmed recommendations. Individual variability seems quite great.
Now you’re asking about how to determine who falls where on the spectrum of possible responses to rapamycin. Frankly, I think this is really uncharted territory. For example, in CR, we have at least some hints, like late life initiation seem not good; those who tend to hold onto more of their weight when on CR do better and some other factors. But rapamycin - no real clues at all. All you can do is to try and see, and even then you really don’t know because of the lack of verified dosing protocols.
Rapamycin is a high uncertainty intervention. With the uncertainty around possible benefits and harms. One small reassuring fact seems that rapamycin appears safe as far as fatalities and great irreversible harm. It appears that stopping rapamycin reverses most of the undesirable side effects.
Anabolic vs catabolic is certainly a dynamic of rapamycin action, but I don’t think one can use that as a global discriminator as to who will benefit and who not. As example, look at the effect of rapamycin on the muscle - rapa inhibits mtor, so you’d think it would have a catabolic effect that interferes with muscle growth. But that doesn’t seem to be the case, and in fact in the PEARL trial there was an actual benefit to the musculature of women, and anecdotal evidence from this site male members seems to confirm that too. Therefore it seems to me that a global anabolic/catabolic discriminator is not going to be predictive of what individual will reap more benefits than harms from rapamycin. YMMV.
