The monkey studies you could write a book about, I wouldn’t make glib conclusions from a few graphs. These studies were extensively discussed on the CR list for years and years. Believe me, when I tell you, it’s very, very complicated. Just a few points: UW showed results favoring CR, NIH not. But as always, is it apples to apples or camels to hunchbacks. The UW had crappy diets - was the good CR result because of eating less crappy food or lower pathologies or slower aging. NIH showed no CR resluts, and the monkeys had better diets, but a very heterogenous group of monkeys assembled from all over the place, survivors from other labs possibly damaged. Sure, take damaged monkeys, and CR can’t do much for them. Then were the NIH monkeys comparing AL to CR or mild CR to full on CR - because what the NIH folks did was to clamp the food supply of the controls so they ate about 20% less than they would of their own free will, that was to prevent obesity so that you could test normal healthy monkeys against CR and not sick obese monkeys to CR. But that begs the question a bit. And mapping to humans, you could argue that we are eating ourselves sick, so cutting back is preventing pathologies, not slowing aging. Then there are the lab shenanigans, where it was revealed that a lab tech sabotaged the whole thing by feeding the monkeys extra food, unbeknownst to the researchers, because they looked hungry to him. It’s a mess. So I’d be careful with looking at a couple of graphs from those studies and reaching far going conclusions. It ain’t that simple.
But getting back to CR and anti-aging interventions. The simpler the organism, the stronger the effect of the intervention. You can prolong a worm’s life by 300+%, but a rat’s by only about 50%, a dog/cow probably 15%, a human’s 10% or as some would argue not at all. The worm has fewer organs, hormones and systems. It’s simpler to dramatically affect the physiology. But for a more complex animal, you have to affect all systems equally. That’s like instead of spinning 5 plates on sticks, you’re spinning 20 plates on sticks. More things can go wrong. Or cannot be affected. The eye lens doesn’t change through your lifespan, and is subject to the laws of physics - you are not going to slow the deterioration by some drug or CR or whatnot. It’s set. And so too limits of how various organs and systems are built - you are just not going to affect them all uniformely.
There is the argument, promoted by some (I think deGrey is one), that short lived species like mice/rats are fundamentally different than longer lived species, since they’re essentially seasonal. If a mouse lives for 3 years max, that’s three seasons. If a season has too little food, it makes sense that the food restriction should allow the mouse to survive until the next season where there is hopefully more food. That could be 1/3 of it’s lifespan. Right there, you have a 33% life prolongation by CR as it allows the mouse to live another season. But what purpose would CR serve in a human that is not a seasonal animal? Why should CR prolong the life of a human by 1/3? It’s not like a season that is going to change the food supply situation. If your food is poor by 1/3 of your life, you should move to where the food is, as the comic Sam Kinison said in response to “people are starving in Africa”. Mice/rats are essentially throwaway species anyway goes another argument - their bodies are supposed to only last for 3 years or so, frankly less, because of predation, so nature didn’t optimize for sh|t as far as making the bodies capable of lasting longer. Good example are possums. Those poor bastards only last about 2 years before terrible old age sets in. Why? Massive predation - so nature just didn’t care to do better with their bodies. Meanwhile, take possums to an island where there is no predation and in some generations, the possums go to 4 years before old age starts hitting. Now, we humans have to last longer - partially because we don’t even mature until our teens and so have to be taken care of and so on. So there was a premium on optimizing our bodies for a longer life. And an optimized body is less susceptible to being massively improved by some drug. It’s already pretty optimized. Meanwhile a mouse is a mess, and any small improvement and whoa, results! It’s starting from a low base. Whereas evolution has kicked our bodies around for some time getting the kinks out. Gonna be harder to improve without going deep into genetic manipulation.
In humans, the CR argument is the same as the NIH trial. NIH trial would argue that a CR effect must be measured against a healthy individual, so one that isn’t overeating. Otherwise, cutting back on food is merely fixing the pathology of overeating. And all those WWII food restriction health effects - are those because the aging slowed or because they weren’t overeathing and eating so that pathologies don’t show up from overnutrition.
But does CR even work in humans, hmm. Which is why there’s another school of thought about how to approach anti-aging interventions. We are essentially a collection of organs and systems, all having their own rates of aging. We always die of something. It’s the weakest link theory. Whatever is your weakest point, that’s what’s gonna get you. Maybe your brain could go on another 30 years, but your heart craps out. Or maybe your heart and body could go on for another 50 years, but your kidneys did you in. Something is going to fail. So how about we detect what our weak point is and fix that, so at least we can last a bit longer. It’s like that anecdote about Ford and his automobile - he ordered his minions to go to the scrap yards and identify what failed in his cars - of course, he was a bastard businessman, so he said “OK, now weaken that which has not failed, because that’s a waste - why make the axel last, at great cost, for 200K miles, if the engine can only hack 150K - save money on the axel, make it weaker and last only 150K”. Now we want to go in the opposite direction. My body can last 120 years, but my heart only 80 - let’s fix the heart. In a roundabout way, medicine is kinda addressing that with saying “let’s focus on the pathologies”, because if we can fix all that is going wrong, we can have people last and last, because people have to die of something and we’re progressively removing the “something”. Or as the comedian Redd Foxx joke: “all those people who eat right, avoid all the good things in life, chicken gizzards, necks, all those delicious things, just so they can stay healthy - they’re gonna feel awful silly lying in the hospital dying of nothing”. Well that’s the idea, we’ll keep fixing pathologies so we don’t have a chance to die. That’s where things like statins enter, CV systems are the weak point of the vast majority of humans, if you improve that, you’ve already prolonged their lives because you addressed their weakest points.
And there you have the fundamental distinction of avoiding/curing pathologies or things that go wrong, and slowing down aging itself. Two different things. And the associated distinction between healthspan and lifespan.
