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Except that the mTOR pathway also promotes growth and preservation of muscle tissue, and we know that muscle tissue is rather important to quality of life and avoidance of injury in old age.


Manipulating the mTOR pathway involves making a trade-off based on your preferred type of death: on the one hand we have frailty, hip fractures, muscle wasting, etc, and in the other metabolic diseases, cancer, CVD, alzheimer's, diabetes etc.

But, you can probably still grow strong enough from life-long resistance training a few times a week+eating enough other (plant) protein. I believe that this is the modern longevity recipe from what we have learned so far from the mTOR/fasting/leucine/isoleucine/methionine research. I hope we soon learn more about optimizing anabolism/autophagy in a targeted way instead of the entire body, that's what it all seems to boil down to.


There is a statistically inverse relationship between diameter of the muscle mass of the legs and dementia[1]. Higher muscle mass has more capacity to store glycogen and in a higher priority than insulin-activated GLUT receptors which in tern means less glucose and insulin spikes. And we do know that high glucose levels are inflammatory.

Point being, a more anabolic lifestyle with higher muscle mass has direct benefits in metabolic syndrome and cognitive decline, so your trade-off is incorrect.

[1] https://jamanetwork.com/journals/jamanetworkopen/fullarticle...


The study you linked to doesn’t support the conclusion you claimed. It provides evidence that low muscle mass is associated with cognitive decline. But it’s presented as a binary - low muscle mass vs not low. There is no talk of a “statistically inverse relationship”, as if adding more and more muscle results in less and less cognitive decline. Intuitively, it shouldn’t be too surprising that critically low muscle mass is associated with issues. Either because it causes decline in other areas or because it is correlated with it (or both). Indeed, from that paper: “Whether low muscle mass is an early marker or a causal factor of executive cognitive decline, and elucidation of mechanisms linking muscle mass to cognitive functions remain to be determined.”


As a daily runner that makes a LOT of sense. I wouldn't have been able to put my finger on it and express it but a similar idea has already been told to me, in another context, in another form.

I also think the conclusion of the research and the poster you responded to is rather wrong. It doesn't matter how long you live if that longevity isn't pleasantly usable. From the elderly I take care of around me, I would rather die sooner from some random disease than live longer and be as useless as they are (both physically and cognitively).


>I also think the conclusion of the research and the poster you responded to is rather wrong. It doesn't matter how long you live if that longevity isn't pleasantly usable.

Agreed. The "human body is a battery" type of arguments are a common misconception and have their roots on the fact that the only positive thing we've found about inflammation so far is that it's an integral part of muscle growth as a response to exercise stimuli/stress via the mtor pathways. But that's a one-off you don't need continuous inflammation to maintain your muscle and enjoy the long term benefits of it.

Oh and the plant based protein is also wrong as that protein is 99% of the time incomplete. You need multiple sources.


A fact that is often overlooked is that the mTOR pathway is activated through resistance exercise.

Interestingly, autophagy and mTOR have an inverse relationship.

In nature there is no free lunch, your suggestion would focus on longevity rather then maximum muscle strength and size.

Although intressestingly enough there also is some research stating muscle size and all cause mortality are linked.

Personally I think cycling nutrition over periods could give the better overall results by not overfitting to one diet and lifestyle.


Very well articulated, You’ve given me that strange feeling that happens when some once expresses cohesively a set of ideas you’re still trying to map


There are also dose-size and age-related dependent components to protein intake.

You want to ingest a decent sized amount of protein to stimulate mTOR instead of ingesting small amounts of protein multiple times throughout the day.

As one gets older, you may need more protein to stimulate/kick off mTOR.

from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882708/ (ref numbers removed from text for better legibility):

"Skeletal muscle mass and functional capacity are controlled by the dynamic interaction of numerous factors, also encompassing diet and nutrition. An adverse yet typical consequence of the aging process is the progressive loss of muscle mass and physical function, named sarcopenia. Although the onset and progression of sarcopenia can be influenced by many factors, a compromised capacity to maintain the anabolic response after dietary protein intake has become a key target for researchers.

Independent of the type of protein and its source, it is important to underline that meals should include an appropriate amount of high-quality protein. In recent years, consensus statements and opinion articles have asserted that protein intake above 0.8 g/kg/day may confer muscle health benefits greater than those conferred by the current RDA.

As such, a protein intake of 1.0–1.2 g/kg/day has been recommended for the preservation of healthy aging muscles, while 1.2–1.5 g/kg/day of protein may be necessary in older patients with acute or chronic diseases. Elderly people with severe illness or malnutrition may need as much as 2.0 g/kg/day of protein.

In young individuals, slowly digested proteins (e.g., casein) may produce greater protein retention than those that are more quickly digested (e.g., whey). An opposite pattern has been documented in older individuals. Accordingly, some authors have demonstrated that the intake of whey protein stimulates postprandial muscle protein deposition in older men more efficiently than casein or casein hydrolysate."


There might be a timing aspect to it - eg by boosting mTOR only in the morning (protein rich breakfast etc).


Circadian rhythm of the body timing is quite important.

There is some research pointing towards that most hunger pangs not caused by daily eating schedule are protein related.


I think it’s multifactorial, but yes, protein is definitely an important part. Impaired gluconeogenesis or glycogen production, or insulin resistance could be other factors there. Chromium, vanadium, zinc, copper, selenium, iron, iodine deficiencies can all lead to problems in those areas. Certain (micro)biome pathogens, too, eg acetaldehyde producers.


Interestingly though, the article says mice on the low-isoleucine diet did better on muscle strength.


It's not exactly what it says. They mention "better shape" but I wish it would be more precise how the jugement is made and what factors are at play. If it's not a hard measure I wouldn't trust their judgment much because of confirmation bias.

There are also a lot of people who consider that anything that isn't extra lean is not good even though we have a lot of evidence that it is actually not healthy. You need some amount of body fat for good hormones regulation, storage and protection.

In the paper, past a certain age the difference in fat mass is not very significant but the control group had much better lean mass. So, it's not that they only lost some fat, the starved mouse are also missing out on useful muscle mass that could potentially make their life better and more enjoyable.

The more I read the more it looks like vegan progaganda...




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