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Eating too much protein and longevity

Someone asked me about Dr. Sinclair appearing on the Joe Rogan podcast:

David Sinclair, the anti aging doctor in the video,  recommends a couple of things in this video for longevity and anti-aging:

Skip meals, Exercise, Limit meat, Sugar, Carbs and he also takes:

1 gram NMN (Nicotinamide)

1/2 gram Resveratrol

Metformin (diabetic drug)

You think he's onto something? For some reason, I feel like you've mentioned those supplements in the past.

Here was my response: 

"I was taking NMN and Resveratrol at one point, but forgot about them probably because they didn't make me feel any different. (Not to say they don't work, I just never remembered to buy more.) I haven't looked into metformin much but am hesitant to try it because it's a prescription drug. I may take them consistently when I'm older. He did say it's OTC in some countries so it's probably not all that dangerous. 

Re: meat
・Sinclair didn't say an amount, but if he means anything less than 1.2g of animal protein per day then I disagree.
TL;DR - Elderly need more high quality protein than young people because their muscles are more resistant to growth and they have a harder time digesting protein. Sarcopenia and poor glutathione production are good ways to not live long. 
You don't want to keep mTOR activation to a minimum at all costs. Not everything that activates mTOR is bad. He recommends exercise. Exercise activates mTOR.

Longer comment on mTOR:
As many researchers like the PROT-AGE study group are finding, the elderly actually need more protein than younger people to support "good health, promote recovery from illness, and maintain functionality" and that a "...shortfall of protein supplies relative to needs can lead to loss of lean body mass, particularly muscle loss."

Furthermore, the elderly need to be eating high quality protein. This means "animal" protein. Quote from a 2016 study: "the current recommended dietary allowance for protein (0.8 g/kg/day) might be inadequate for maintaining muscle health in older adults, probably as a consequence of “anabolic resistance” in aged muscle. Older individuals therefore need to ingest a greater quantity of protein to maintain muscle function. The quality of protein ingested is also essential to promoting muscle health." The PROT-AGE group recommends at least 1.0-1.2g of protein per kg of body weight per day. 

Unfortunately Dr. Sinclair didn't really elaborate on this mTOR thing that connects to a ton of other puzzle pieces. Without adding nuance, these mechanistic arguments are like:

"Everybody wants a dog that doesn't poop. So, we looked for ways to minimize pooping. Not providing food to the dog was the single most effective intervention our research group tested. Later studies found that while zero pooping was achieved, the dog died."
It's a lot more complicated than "mTOR activation is bad. So, things that activate mTOR are bad."

-We don't want to reduce mTOR at all costs
-Ironically, protein is really important for the elderly to stay healthy for many reasons (see PROT-AGE below)
-Caloric restriction/avoiding overeating is a very robust way to increase longevity. Protein is very satiating. 
-You want to avoid too much mTOR activation, but you still want some (see David Sabatini image)
-There are better ways to keep mTOR activation in check. For example, insulin is a stronger activator of mTOR than amino acids. (Which falls in line with Sinclair's less carbs and less sugar recommendation)
-Context matters. Are you eating your protein between two hamburger buns or are you eating a steak by itself? See this 2011 study: The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway

-Less mTOR activation does seem to increase longevity.
-As Dr. Sinclair said, protein does activate mTOR ...but as mentioned above we need protein to maintain good health in old age. The production of the most important endogenous antioxidant, glutathione (far more effective than blueberries, green tea, etc.) relies on amino acids.
-Exercise activates mTOR ...but It's widely agreed upon that exercise is fantastic for improving health and increasing longevity. 

mTOR is regulating this often seen tradeoff between growth and longevity. It's a balancing act. You don't just want less and less mTOR activation because after a point, your health will suffer. mTOR researcher David Sabatini has a nice image: 

(Looking at the graph, Rapamycin really lowers mTOR activity, but this suppresses the immune system. Rapamycin is used for organ transplantation - to suppress the immune system enough that their body doesn't reject the new organ.)

As Dr. Chris Masterjohn said, the vegan doctor T. Colin Campbell did several studies on protein's effect on cancer. He found that more protein fuels more cancer when the cancer has already been established. What he doesn't talk about is that he also found that if the animals don't already have cancer, more protein prevents cancer. In fact, protein was protective even if you were giving it to the animals while they were being dosed with a carcinogen. Masterjohn says the reason why protein is so protective is probably because the amino acids, especially those found in animal protein, are key to the production of glutathione which is key to antioxidant defense and to detoxification."

Comments

We're is the graph/image from David Sabatini??

I've watched a couple of talks by Sinclair on YT, but am skeptical of his ideas, especially taking metformin. I might be misremembering, but I think intermittent fasting has some similar effects to metformin. Also, were there supposed to be some images?

Mark Simonson


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