Blagosklonny on protein

This is worth a discussion.

In case the Twitter link doesn’t work…

“Protein restriction is bad for you
When started very very early in life protein restriction may slow mTOR-driven developmental growth, increasing longevity. Thus, methionine restriction in childhood (MR) increases lifespan in numerous species but data are conflicting. Now we know why. Lifespan may be limited either by poor fitness or by aging. MR decreases fitness but slows mTOR-driven aging. MR decreases body temperature, IGF-1 and glucose levels and deactivates the AKT/mTOR pathway in normal mice {Barcena, 2018 #87}. MR decreases fitness but slows aging. In normal mice, MR slows growth and weight gain and increases risk of death in the first year of live (Fig in Miller). Some MR mice died from rectal prolapse, which is not an age-related disease {Miller, 2005 #71}. But surviving mice lived longer because MR slows growth and aging, which is a contituation of growth. (Note: the authors’ conclusion was different but their data support my re-interpretation). Similarly, sulfur amino acid restriction (SAAR) decreases levels of Insulin and IGF in rats {Nichenametla, 2020 #88}, thus slowing growth and aging. SAAR-induced lifespan extension occurs at the cost of growth. It prolongs life span dramatically, when started early in life. In old mice group, its longevity effect is not even statistically significant ( p=0.0504) and 5 times less than in young mice group {Nichenametla, 2020 #88}. This result is consistent with the notion that aging is a quasi-program of developmental growth. (Note: the authors’ conclusion was different but their data support my re-interpretation). In Drosophila essential amino acids (EAA) shortens lifespan and rapamycin prevented this effect. In other words, EAA decrease longevity by activating mTOR. Yet, EAA increases fitness and heat stress resistance, also by activating mTOR-dependent (abrogated by rapamycin) {Emran, 2014 #77}
For us, adult humans: Combine protein diet with rapamycin”


The important thing is measuring strength and muscle mass and other indicators for frailty. These discussion ex ante are based on mouse and human studies. If you measure what’s important you can have as low of a protein intake as possible.

If strength/muscle mass is under optimal, you can increase protein intake and measure the result. This seems the wisest approach. Since it declines over time the optimal range can be higher earlier in life.


My takeaway is that one should cycle between periods of low mTOR and high mTOR to gain the best of both worlds. During the high mTOR period, one could consume high amounts of protein combined with a series of good workouts to build muscle mass. During the low mTOR period, one could combine rapamycin with calorie/protein restriction to promote autophagy.

There is an interesting discussion of fitness vs aging in the tweet. I think I agree with the sentiment in favor of fitness, i.e. having more muscle mass than may be optimal from an aging perspective. Beyond functional benefits, muscle also serves as a reserve of protein, which is a major factor in one’s ability to survive traumatic accidents (a leading cause of death in my age group). I will say that there are some incredibly jacked dudes at my local gym, for whom I have great respect for their mental drive, dedication and lifestyle optimization needed to achieve such levels of muscularity. But there is definitely a point of overdoing it when the sheer mass of the muscle affects your ability to sleep.

I would also say that from a longevity perspective, it’s better to carry muscle mass in your lower body, which is less likely to affect sleeping, lowers your center of mass and strengthens your legs to prevent falls, whereas folks (myself included) focus more on upper body at the gym.


IMO: It is critical when you grow old to maintain muscle mass and strength in your legs. This is one of the main things that keep you mobile and out of nursing homes.


Far more complex than simple muscle mass. It’s all the little muscle that help you with balance. It’s practicing balance to use those muscles and test your proprioception. And don’t forget upper body, you will need that when you do fall.


Some people knowledgeable in this area disagree with Blagosklonny:

An interesting take, but the frail elderly don’t do well.


This debate is lacking nuance. Nobody disagrees that strength, anti-fraility and muscle mass is important. The question is how to get there. On one hand there is an anti-protein camp that says that low protein diet along other things is important. Another camp is pro-protein which cite studies showing when there is optimal muscle gain. It depends on the situation.

Someone who is lacking in strength, is frail, lacks muscle mass needs to eat high protein to increase growth of muscle mass as soon as possible.

Someone who doesn’t, and is in a preventative phase have all the time in the world to find what protein intake works best for them and their markers of strength, muscle mass, and biomarkers.


How much protein you need as a minimum likely different than what is best. It likely changes by your age. And it varies by what your goal is.
Im sure people in blue zones get by on low protein and have long average lifespans. But having muscle mass as an individual may be what saves you when you fall.

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Isn’t it bone density that saves you, the last defender? Kids fall all the time but never break their hips.

Muscle mass might be a proxy for bone density, or slightly help with falling more gracefully. But for the latter I think reaction time matters more to slow down a fall with arm etc, or ?

So this is the real reason dwarves and midgets live so long? The rest of us have too much momentum when we fall?

I agree with this.

I’m 28 years old and I take rapamycin weekly. Ive been wanting to gain some muscle mass which requires me to up my protein intake to gain muscle mass. However due to the recent videos/articles about protein being bad for longevity due to MTOR ive been hesitant about taking protein so I’m thinking about doing low protein intake on the first 2-3 days of taking rapamycin & for the remaining 4 -5 days i’ll train in the gym & up my protein intake to support muscle mass. So if i take rapamycin monday I’ll go low protein/animal products from monday to Wednesday and from thursday - sunday (gym days) I will up my protein intake to support muscle growth after the gym.

Curious to know if anyone else does something similar?


Funny, and true. Nor do mice have to worry about falls.

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Alternatively take protein supplements when not on rapamycin. You may try 4 weeks on rapamycin and then 4 weeks off when you do your supplements and stimulate growth.

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My visits to nursing homes suggest they are filled with frail people with little muscle mass. Does this mean people who have muscle mass are able to stay out of the nursing home? Or does it mean they died earlier? I’m betting my life on the former: if I can cycle MTOR on and off with heavy exercise and Rapamycin/fasting I can get the best of rejuvenation and survival, and stay out of the nursing home.

I also think if we really want to have this discussion about protein and muscle mass, we not only need to discuss where the muscle mass is built (yes legs are critical, but I see core and back as critical as well; you can have t-Rex arms and survive fine). But even more critically (and I didn’t understand this until I started lifting heavy weights) there is a massive difference between “muscle size” (volume) and “muscle strength” (the amount of weight you can lift, or the speed/impulse you can generate). There are many “gym bros” (or “lunks” as Planet Fitness calls them) with huge muscles and can’t put their arms down, but many of them can’t lift as heavily as people who look more reasonable but train specifically to lift heavily. So there must be a difference in either muscle density or biochemistry between these groups. (The anabolic steroid usage seems to favor “size”). Does this difference show up on a dexascan or other test? I assume the “strength” is better for longevity than “size” but I don’t think there’s been a lot of research on this.


I agree. Functional strength and coordination is the key. Ability to:

  • balance without looking (turning to look for oncoming cars)
  • catch a stumble (when stepping over a curb)
  • get up from the floor
  • walk up stairs with groceries
  • walk on a slippery surface (snow, ice)
  • catch a ball
  • etc

A deadlift or other heavy lifting might not be functional but is a way to build a reserve of capacity (have room to decline).
Upper body muscle isn’t as important as lower body or core but is still an important

I also periodization my protein and resistance training to avoid rapa dosing. Low protein and low calories on rapa day and +1. High protein on resistance training days. I do zone 1 & 2 endurance work on non resistance training days. As Attia says, “everyday is leg day”.


The swole folks might have died early, but the rest probably got caught in a pernicious cycle of frailty. Once basic movement starts to go, it screws up everything and so it’s hell to rebuild. I’ve expressed my doubts about building size in excess of that needed for quality movement elsewhere – I don’t think there’s much evidence to support that. On the other hand, IMO you should prioritize being able to do things at the level of, say, a median 30 year old. This includes dynamic skills like falling safely.

I agree. It should be said that falling can be minimized but not avoided. Shit happens, as they say. I plan to be good at falling, and at having strong bones, and good muscle mass to spread and absorb the impact of falling. I can remember my Judo teacher shouting at me to “slap the mat”. I’ll be doing tumbling and fall training. Just getting down on the floor gracefully is a start. In cycling, my teams always had falling courses to teach people how to fall well. In cycling, if you are racing, you are crashing.


Out of curiosity, how do you practice cycle specific falling? Martial arts training let me walk away from my last fast crash. Or luck, TBH, but one likes to feel in control.

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We used gymnastic mats. Progressed from rolling to falling while walking (into a roll) to falling while riding (into a roll).

Generally, when you go down on a bike, tuck your arm under you to roll when you hit instead of putting the arm out to catch. Don’t land on shoulder either…think in terms of landing on your back. Hear a helmet of course.

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