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Really interesting talk, with a main thrust that isoleucine shortens lifespan via a range of mTor-mediating genes. But in the context of therapeutic rapamycin, would isoleucine have the same effects, or would the benefits of low isoleucine be minimal when one is taking rapa?
I read Attia’s email today, where he doubles down on optimal protein intake being 1g/pound of body weight (which for muscle growth in the context of intense resistance training, is probably true). It’s interesting to note that he mentions his discussion with Layne “dispelling the myth that extra protein causes cancer” but notably says nothing about high protein and the aging process itself. This seems like selective avoidance (whether conscious or unconscious, I don’t know).
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We know that under the age of 65 that protein increases IGF-1. Levels of IGF-1 over 160 are a significant cancer risk. If you keep protein intake between 50-80 grams per day, you’ll hit the sweet spot of IGF-1 between 120-160.
A gram per pound per day is very high and not necessarily indicated even for muscle growth.
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Thanks for that video! I’d really like to see a study where they selectively lower both methionine and BCAAs (or even specifically just methionine and isoleucine) to see if there are additive or synergistic benefits to health and life extension.
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Morgan Levine touched upon the issue of longevity diets in her recent Wired interview:
What is the secret to longevity?
Laughing my ass off.
Actually, longevity science says plant-based diet
is probably the best diet.
There’s a lot of evidence from both epidemiological,
which is the science when you actually look at populations,
as well as some more emerging clinical trials,
that suggests that a diet rich in mostly plant-based foods
can actually extend your lifespan and prevent disease.
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Thanks RapAdmin
Good stuff. The evidence is getting overwhelming. I don’t know or communicate with Peter Attia, and he’s not here to give his viewpoint, so I can’t comment on his take on proteins.
As an aside, I also get this occasional small rash since rapamycin. No idea what to make of it.
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And maybe , in terms of life extension, there’s something to this idea of just eating during the day and stopping in the evening. Thirty five percent is alot!
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Couldn’t agree more. Case in point: my buddy got a personal trainer who also pushes high protein consumption. I told him protein accelerates aging. He said:“Yeah , my personal trainer is 30 , but he looks like he is 40 at least!” Buff and cut, yes. But at an obvious cost!
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Why is fat worse? No insulin response, no mTOR response.
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I tried acarbose for a while. Didn’t seem like it was something one should do. Just felt weird in my stomach. Decided to just don’t go crazy on carbs instead.
Canagliflozin is much easier in the GI tract.
Thanks for sharing the link to the interesting talk by Dudley Lamming. At the 5:00 minute mark, he states, “Restricting isoleucine is necessary and sufficient for the effects of protein restriction.” … “In fact leucine restriction may be slightly detrimental.”
At the 11:00 minute mark, he states that higher isoleucine intake in humans is associated with higher BMI. He shows a graph from a paper at the 11:40 minute mark…look at Leucine…higher levels were associated with a lower all-cause mortality risk (HR = 0.82).
From that research paper: “For the total lipids in chylomicrons and extremely large VLDL and small high-density lipoprotein (HDL), the mean diameter for VLDL particles, the ratio of polyunsaturated fatty acids to total fatty acids, and the concentrations of histidine, leucine, valine, and albumin a higher level is associated with decreased mortality, while for the concentrations of glucose, lactate, isoleucine, phenylalanine, acetoacetate, and GlycA the opposite applies.”
Here’s a link to the full text of the paper:
A metabolic profile of all-cause mortality risk identified in an observational study of 44,168 individuals
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Yeah I’m trying to take this these into consideration when it comes to optimizing the cycling of mTOR activation (for muscle growth, sufficient short-term immune function) and mTOR inhibition (for autophagy, lipolysis, long-term immune function, and all other things longevity).
On a monthly scale, regular FMDs OR fasting protocols are one way to do this. Perhaps FMDs can then be low carb, low protein (and especially low isoluecine and methionine and histidine – I think vegan diets may help here).
On a shorter time scale, perhaps diets with low isoluecine + methionine + some berberine/metformin on inactive & sedentary days.
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Is there a way to direct a question at Dr. Blagosklonny? At times he seems to be responding to people on twitter. Though, if a question about optimal diet is directed to him, from what I have read thus far, I think he will answer that his concerns are high simple carb limitation and general calorie control (ie weight control). Still, it would be valuable to get his opinion. I don’t know if this site would even exist if it were not for his work.
I can’t speak for him, but I get a feeling that he thinks these are not relevant or important questions if one is taking (sufficiently high doses of) rapamycin regularly. The logic being that any harms of mtor activation through protein would be attenuated via rapamycin, and we may not want to skimp on essential amino acids. He does seem to however still support low-carb diets; perhaps the belief here is that carbohydrates and insulin spikes contribute more to mTOR activation via AMPK than proteins.
While all of these may be true, I think it’s still good to seek deeper understanding of what’s at play so that we can if possible, further optimize our approaches to longevity, and so that we can use different interventions in different situations than be constrained to just use rapamycin (despite my love for it). Given that Blagosklonny has proposed anti-aging cocktails, I believe he’d think so too, but just not so much about dietary protein.
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This mirrors my thinking perfectly.
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Maybe we’ve been focusing far too much on the composition of diet- in large part because weight loss is the goal.
Maybe just eat generally less and eat according to a circadian rhythm while awake and active during the day. Stop eating later in the day when you get more sedentary. Don’t worry so much about counting grams of protein, fat, and carbs.
Limit the sugars and processed foods.
The circadian rhythm of diet may be as important as that of wakefulness and sleep.
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Recent article on Intermittent Fasting and cancer risk:
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Protein is complicated. Yes, it signals abundance, which shifts away from maintenance and towards proliferation. But it also preserves muscle mass, and given how big a risk factor frailty becomes as you age that’s a very significant counterweight.