Right. These however are not mutually exclusive. Even if longevity drugs donât prevent modern lifestyle death and disease causes, they still work. Btw., true longevity drugs are supposed to work by slowing ageing, which delays these diseases, and there seems to be evidence that at least in animal models rapamycin does so. To me, rather than dropping longevity drugs, this is a reason to escalate the use of drugs that prevent or ameliorate these diseases, like statins and the like.
Rapamycin - or longevity drugs - are like a healthy diet, we know that a healthy diet leads to a longer life. But what if you live in an unsafe neighborhood, and there are regular shootings? Would you say âgee, Iâm not going to bother with a healthy diet, because a healthy diet does not prevent my being shotâ. The solution is to keep the diet and move your place of residence. Same here, just because rapamycin does not prevent modern lifestyle diseases (and Iâd dispute that, at least in animals), doesnât mean it makes sense to drop it. Dropping rapamycin will do nothing to cure heart disease, cancer or T2DM.
However, there is a much more interesting argument, brought up by Matt Kaeberlein. What if rapamycin both slowed down aging and killed you prematurely? That might very likely be the case. Now you truly have a dilemma⊠except the solution is very simple.
How can rapamycin delay aging and yet kill you way ahead of your natural time? Because while rapamycin slows down your aging, it also, especially at higher doses, might depress your immune system and you might die of an opportunistic infection. In lab animals you donât see that, because labs take pains to shield animals from pathogens. So whatâs the solution? Drop rapamycin? No, the solution is the same as with the diseases above. Retain rapamycin (although you might want to mitigate the danger with dosage), but get all the vaccinations you can for pathogens you might be exposed to, and minimize unnecessary exposure to such pathogens in the first place. Win-win.
Same with the diseases you mentioned. To me thatâs a compelling argument for carefully curated polypharmacy. I take rapamycin, but I also take a bunch of drugs to ameliorate the chances of my getting these diseases: lipid lowering therapies (statin, bempedoic acid, ezetimibe etc.), blood sugar control (SGLT2i, soon pioglitazone, perhaps acarbose), blood pressure control (telmisartan down the line). Exercise and a good diet are a given - Iâd do that regardless. Itâs not an either or. I want maximum impact on healthspan and if lucky maybe even lifespan, and the first step is diet, exercise, stress and lifestyle adjustments. But that only takes me so far. The next tranch is taking medications proven to enhance healthspan or lower health risks: lipid control, blood glucose control, BP control and vaccintions. And then I roll the dice with a cherry on top: longevity drugs - thus far rapamycin, but weâll see what science brings us in the future. Iâm not dropping the longevity drugs just because other risks exist, I lower the other risks instead. Furthermore, we have evidence from the ITP that many of these work synergistically: rapamycin works even better with for example an SGLT2i, acarbose, metformin etc.
These lifestyle drugs (statin etc.), get me into the door of the casino. Rapamycin gets me some chips I can place on the roulette table. I for one am not going to reject the rapamycin gambling chips. I am gambling that Iâll come out ahead instead of going bankrupt, but thatâs the nature of the game. YMMV.
EDIT: incidentally Matt Kaeberlein published a short on yt. contrasting short term vs long term effects of rapamycin in mice. Short term, there were metabolic derangements of glucose control, but longer term there was an improvement in these parameters compared to the baseline. A nice illustration of why it is important to focus on long term outcomes and not short term mechanistic perturbations in evaluating these drugs:
