Rapamycin: an anti-ageing medicine?
The conventional wisdom of protein maximisation is wrong. It's good to be a soyboy
Suppose that there is one compound that has the potential to be a universal drug to delay, or possibly reverse, ageing? Rapamycin, which inhibits the mTOR (mechanistic target of rapamycin) enzyme, is a strong candidate for such.
In animals, mTOR plays a focal role in promoting cell growth and modulating ageing, at the cost of inhibiting autophagy, and to the extent where this may possibly promote cancer and neurodegenerative diseases as we age. Indeed, it's the only known treatment that extends longevity in every single model organism studied, and the autophagy mechanism via which mTOR signalling promotes ageing easily generalises to us primates too. However, the results appear to be influenced by antagonistic pleiotropy to some degree, so some reported benefits disproportionately accrue to the relatively old. Nonetheless, it’s in old age when chronic diseases play a salient role in our lives, so any mitigation of this suffering and tragedy is in itself invaluable.
If rapamycin is such a promising pharmacological substance for promoting longevity, then why isn't it more widely prescribed? After all, it is an FDA-approved medication to prevent organ transplant rejection and sometimes in the treatment of cancer. The answer: some side-effects yield tangible costs to our healthy wellbeing. For instance, as an immunosuppressant, it increases our risk of infections. Henceforth, until pharmacology resolves this issue or makes the tradeoff more palatable, perhaps we want to inhibit mTOR signalling indirectly, via our lifestyle choices?
Recurring throughout this series once again, the literature cited above has suggested calorific restriction as a solution to restrict mTOR signalling. In the absence of GLP-1s [1], human nature renders this a task that (for many) could be as painful as ageing itself. Fortunately, protein restriction may be a more potent longevity booster than calorific restriction per se, as amino acids, the building blocks for proteins, are the primary “switches” for mTOR signalling. Calorific restriction boosts AMPK, which inhibits mTOR, yet this is a more indirect mechanism.
But hang on? Aren't we always told to focus heavily on amping up our protein in our diet? Perhaps if you're a bodybuilder, but for those of us that care about fundamentals over deceptive appearances, most of us exceed the recommended levels - raising our risk of cancer [2][3]. Those consuming “low protein” diets such as vegans actually meet the optimal intake (animal proteins, owing to a different amino acid structure that triggers IGF-1 and mTOR more easily, are substantially worse than plant proteins) [4]. Although (as IGF-1 and mTOR levels rapidly drop in old age anyhow) some frail subpopulations such as the elderly may benefit from a protein maximising strategy, for most of us that is a one-way ticket to cancer.
In particular, the amino-acid methionine, crucial for protein synthesis, activates mTOR whilst suppressing autophagy. Concentrated in the animal protein food groups, it makes sense to minimise our consumption of those. Leucine, another amino-acid and potent mTOR activator, tends to be concentrated in milk and meats. In other words, we should go as vegan as our tastes will allow. This is not denying the ubiquitous succumbing to temptation prevalent amongst those whom attempt this, yet we should reframe our consumption of meats, eggs and dairy [5] to a habit more analogous to drinking or eating confectionary. If you consider animals as sentient beings, there is a strong ethical case for such anyhow, especially in tandem with what we know about protein restriction and the health benefits of veganism.
So we've established what foods we seek to avoid or minimise. I have no need for dairy milk or yogurts, so I can easily substitute them for their oat or soya equivalents. The rest is a case of minimisation and restriction, rather than abstinence altogether - corner solutions are rarely feasible. Nonetheless, what do we want more of? Sulforaphane, concentrated in cruciferous vegetables, suppresses mTOR activity. Green tea, my favourite beverage, is likewise a powerful inhibitor of the ageing hormone.
Socialised medicine in Britain, and the NHS’ reluctance to purchase these agonists at market prices, result in strict eligibility criteria for prescriptions. Consequentially, our country still has an obesity problem as a result of this shortage. Private providers will supply GLP-1s for £150 to £350 (about $200-500) per month, yet the NHS and the taxes that fund it crowd out private expenditures.
Stimulating IGF-1 signalling is another mechanism via which excess protein consumption reduces longevity, yet the causal literature on this is more tenuous at this stage so I haven't cited it.
Ironically, testosterone also activates mTOR signalling, which may in part explain why men tend to have lower life expectancies than women. With keto diets (which cause endogenous acetone production; accelerating AGE accumulation) being a scam, steroids bad for longevity, and protein restriction good for longevity, it appears that we actually want to avoid the bodybuilder lifestyle. Turns out being a soyboy is how you maximise your lifespan!
If there are protein deficient vegans, then that may be owing to their consumption of ultra-processed vegan crap as opposed to tofu, legumes, edamame, soy, seitan, and the like. The idea that one cannot easily obtain a sufficient amount of protein on a vegan diet is a ridiculous myth, as East Asian countries demonstrate.
As mentioned in my last post, fish is rich in Omega 3 (unlike other foods) so I might make an exception here, although a vegan diet is anti-inflammatory anyhow.