How important is muscle mass?

[CR Curious]

Hi everyone,

I'm new to the forums and very impressed with the level of engagement and sophistication. I wasn't expecting to be convinced that we don't have good evidence that CR works in humans on a CR forum, but I was.

That said, my read of some of the forum posts (and other evidence) is that:

• People tend to think that the evidence suggests fasting is probably good. That means shrinking your eating window down essentially as much as possible and possibly doing some extended (e.g., 5-day fasts).
  • Though Longo continues to insist that 12 hours of fasting and 12 hours of feeding is good. He seems to be an outlier.
  • David Sinclair is into OMAD and seems to think that fasting is the key but I think I've seen some stuff suggesting that he buys into CR but thinks it's too hard.
• People tend to be bullish on protein restriction as a strategy for slowing aging. So eating vegan, keeping protein around 10% of diet. Longo/Fontana stuff.
  • But some folks on the board seem to be vegan for ethical reasons. That's great, but I do worry that there may be motivated reasoning when it comes to the health effects of animal protein.
• Both of these things would tend to support the mechanistic stuff about mTor/IGF-1/etc. This is the very basic growth/longevity tradeoff model. Protein turns on pro-growth signaling but that's bad for longevity. Fasting/eating less protein promotes autophagy. Hormesis. Etc.

Now, I'd welcome feedback suggesting that, like Dean's post on CR in humans, the evidence for these propositions is weaker than some make it out to be. Of course, nothing is clear cut but the question is whether the totality of the evidence is strong enough that it's worth acting on. I used to think that was true of CR (though whether I had the willpower to actually do it was another question), but now I think the evidence is basically 50-50 on whether it'll work in humans relative to a diet that doesn't make you fat. So I'm not really going to put in extra effort to do CR.

But my impression is that, though the evidence is not slam dunk by any means on fasting/protein restriction, there's enough that it's worth doing.

Here's my issue, though. There's the Peter Attia view that we should prioritize preserving muscle mass for healthspan. (This seems to be what he currently thinks; Attia has changed his views a lot.) And indeed, there's good evidence that muscle mass is important for longevity/healtspan. And there are a lot of exercise researchers (Stuart Phillips, Layne Norton) who think eating high protein is important for longevity. Rhonda Patrick has had some of these kinds of people on her podcast recently. These kinds of folks talk a lot about frailty/sarcopenia.

Now, I know that Longo says increase protein after 65 for this reason. But Attia makes the point that we know muscle declines with age, so we want to be starting from as high of a baseline as possible. Which would imply building muscle early in life is optimal. 

The problem is that the muscle-building diet seems to be the exact opposite of the OMAD/protein restricted diet. There seems to be good evidence that ingesting protein leads to a transient increase in muscle protein synthesis, so the way optimal to build muscle is to eat protein (especially animal protein because it has lots of leucine!) at regularly spaced intervals (and do strength training, of course). And of course, that makes sense if the basic growth-longevity tradeoff model is right.

Have others thought about this? I expect that there is some unavoidable tradeoff here, as the growth-longevity model would imply. But does that mean that a shorter eating window isn't necessarily better? How much muscle mass is enough to avoid age-related issues? Might higher protein make more sense after strength training? One thought is that regular strength training will be enough so we shouldn't worry about muscle building on the diet side. But I'm not sure.

I'm 30/yo, male. I do OMAD for the longevity benefits and exercise a fair amount. I also strength train 3 times/week primarily for longevity. (I run a lot, too, more than I would if I were just concerned about longevity.) I eat a pretty high protein diet with lots of animal protein but am thinking about trying to reduce. My approach has pretty much been trying to split the difference by eating high protein for one meal, usually timed so that I eat as soon after strength training as possible. (I find that protein is good for satiety, so high protein diets may be better (at least for some) in reducing body mass.) But I am curious if/how others have tried to split the difference here.

 

[Guest]

These are very valid questions.

 

You don't need to dive into the science of CR (specificially methionine restriction), to get statements from some well known researchers in the field advising against eating "too much" protein - often in a context of discussing autophagy, mtor-suppression or IGF-1-signaling.

 

Going strictly by data from humans, it seems the Attia-camp has a stronger backing than the Longo-camp:

1. data for the behavior of autophagy in human basically doesn't exist; there is one (1) study investigating the effect of a multi-day fast on AP in skeletal muscle; the increase of AP in humans was minuscule compared to even a 12-hour-fasting-mice

2. mtor-intervention similarly lacks data in humans (or any longer lived species other than mice)

3. growth hormone activity seems to suggest, that it favors lower levels for longer life.... but: that's all based off cohort genetic data, i.e. small people vs. tall people etc. and not even Mendelian Randomization - so it's rather fuzzy what it means for a tall person vs. another tall person to adopt a certain lifestyle

 

But we do have observational data comparing similar groups of people with differing muscle mass and strength; these studies (again: only observational) show a strong association between being, well, stronger, and decreased mortality in old age. Depending on the metric and study design, people in the lowest percentiles had a 70%-300% higher mortality rate - after adjusting for con-funders like smoking or pre-existing conditions. Still just observational, yes. But the effect size in the studies is so gigantic, that it's probably not completely false.

 

[Ron Put]

I listen to Attia and I find his show and opinions useful, but he is not a researcher and a many of his guests make claims that may not all stand up to scrutiny, perhaps because they have axes to grind, or stuff to promote and sell.
 

5 hours ago, Guest said:

But we do have observational data comparing similar groups of people with differing muscle mass and strength; these studies (again: only observational) show a strong association between being, well, stronger, and decreased mortality in old age

I am not sure that this generalization is necessarily true. Old-age frailty is not necessarily due to not lifting weights when 30, but is more likely a consequence of genetics, life-long habits and subtle changes that may not raise to "pre-existing conditions" but have an impact on mobility, ability and desire to engage in activities that would stave off frailty, etc.. Perhaps there is correlation with overall mass, but weightlifters or even folks with Attia's physique are far rarer among the very old than those with slighter builds.

I probably would not suggest CR at 30, especially for someone who is healthy and fit. While I am a vegan nowadays for moral reasons, I have observed significant measurable health benefits since I stopped consuming animal flesh, and then slowly moved away from animal products. I would venture a guess that high-amounts of animal protein are not the secret to longevity.

[IgorF]

I think it could worse to add let's say a third way of seeing things, the one described in the "Excercised" book - our bodies are evolved to do a lot of walking, a bit of running and chores. Almost all the day. For hundreds of thousands of years our bodies were tuned for such activities and energy available in the tubers etc. was the rate limiting factor for the population and brain development that is stimulated by population density. Then agricultural invention changed the things and so on. But for our bodies to adopt it could take much longer time naturally, so they are still tuned to operate in a slight deficiency of energy and that is the most common wisdom / Occam's razor argument for doing weight control / very mild CR regimen to try to get max from personal genetics.

Hard CR looks like self-induced persuasion of some people that sometimes could persuate some others but there were no strong enough arguments to persuate the majority of scholars, despite the price of the potential achivement is of the highest grade (and this potentially deregulate scepticism for some).

 

Br,

Igor

 

[mccoy]

I've been listening attentively to the muscles/protein issue from both sides. My considered thought is that the middle ground governs. Also, as we have discussed, the individual variability in protein (and other nutrients) requirement is wide, even by excluding the strength-training confounder.

Skeletal muscle: there is no doubt that it has a positive effect on well-being and longevity, but that's true of cardiorespiratory fitness as well. Everything in the body seems to benefit from both exercises, strength and cardio. Even the brain, but that's maybe almost natural, given the increased oxygen flow, the neurologic stimulation, the release of chemicals like BDNF .

I am a huge supporter of optimization. Most of us have not very much time and even if we had, after a certain age the musculoskeletal system often starts to feel the physical 'abuse': too much running, too much weightlifting, too much mechanical stress. 

Also, the response of muscles is very different individually. I am apparently genetically prone to muscle growth, I only weight-train twice or thrice a week, for a weekly total of 1 or 2 hours max. To me, muscular development is already optimized. I also feel that much protein is not needed, I let the instinct/neurological signals, govern.

For others, it may be futile to try and develop big muscles. A modest amount of well-designed exercise will bestow anyway great benefits, by stimulating some hypertrophy, by strengthening bones, muscle and joints, and so on.

Bottom line: who is right? Longo/Fontana, Layman/Attia, and so on.... To me, nobody and everybody. We just have to pick the best of them and optimize according to our own setup.

 

[Sibiriak]

12 hours ago, CR Curious said:

There's the Peter Attia view that we should prioritize preserving muscle mass for healthspan.

I would aim for preserving neuro-muscular quality,  not simply muscle mass.   If the goal is to maintain physical functionality  through old age,   you don't  actually need that much muscle mass per se to achieve that,  and furthermore,  there is a lot of evidence showing that the loss of muscle mass per se is not the driving factor in the loss of functional strength, balance etc.     

Unfortunately, I don't have the time to link the various threads that have delved into these questions.

Edited February 17, 2023 by Sibiriak

[mccoy]

Sibiriak, do they have a rigorous definition for neuromuscular quality? AFAIK, the neurological component of strength is less dependent of muscle mass. Maybe this is referred as to neuromuscular quality.

I know that handgrip strength, yes, this apparently weird parameter appears to be a proxy for neurological strength (don't know if it is the same thing as neuro-muscular quality) which appears to be associated to lesser mortality. Actually, in the literature they often cite muscular mass together with strength, two variables which are not independent at all, one can be used instead of the other (although it's clear that they have not a perfect positive correlation).

I would say that greater muscle mass usually automatically implies greater strength so it's generally a valid pro-longevity parameter. It may happen though that in some individuals lesser muscle mass has greater strength than bigger muscles, then it may constitute a better pro-longevity indicator. 

Also, we have handgrip strength and relative handgrip strength, which is hand grip scaled to body mass and if we consider this latter parameter, changes in mortality from the lower to the higher quartile are less evident.

Another confounder, are we speaking of untrained, or trained people, or both, should they be treated separately?

Bottom line, the issue is complex, I don't know it studies exist which separate neurological strength and muscle mass and define mortality accordingly.

 

[CR Curious]

Thanks for the pointer, Sibiriak. I searched and found at least one thread where you discussed this. Seems convincing that the high (animal) protein/muscle building diet does not make sense! I wish more forum users had weighed in, though. I wonder what the Attia crowd would say in response?

• Some examples of Attia's arguments:
  • https://peterattiamd.com/dispelling-myths-protein-increases-cancer-risk/
  • https://peterattiamd.com/are-you-eating-enough-protein/
  • https://peterattiamd.com/category/nutritional-biochemistry/protein/
• I'm particularly interested in whether anyone has arguments responding to the top clip with Layne Norton (there are notes below the video if you don't want to watch it). It has a provocative title--"Dispelling myths that excess protein intake increases cancer risk"!
  • One argument in there is that there may be a difference between an acute and chronic rise in mTOR/IGF-1.
    • I've seen other folks like, e.g., Kaeberlein who does all the research on rapamycin argue that cyclical mTOR activation might be optimal.
    • And that might suggest that, e.g., doing TRE with animal protein could be good--keep mTOR low generally but really go for it when you activate! So maybe OMAD with a fair bit of animal protein (which is what I've generally been doing, though not really for longevity reasons) is one way to approach it.
      • There's a book called The Switch that also takes the view that we should cycle between anabolism and catabolism. 
  • Another thing Layne Norton points out is the meta-analysis that showed no ill effects on people who ate a lot of meat but also ate a lot of fruits/veggies.
• FWIW, Rhonda Patrick has discussed this issue a fair amount, too:
  • https://www.foundmyfitness.com/episodes/brad-schoenfeld
  • https://www.foundmyfitness.com/episodes/stuart-phillips
  • https://www.foundmyfitness.com/episodes/how-much-protein-should-you-eat-muscle-growth-vs-igf-1-longevity-concerns-rhonda-patrick
• The top 2 clips are just interviews, so I wouldn't say that RP has staked out a position on this issue but I think it's something she's thinking about.

 

Thanks to all who have responded thus far! I'm deeply grateful that you are sharing your knowledge!

 

 

[mccoy]

I simply find that I'm not able to sustain a hi-protein diet for long. Maybe I could ingest the amounts suggested by Dan Layman if I ate protein first, satiate with it, then eat little vegetables and nuts. This would have undesired effects though, first of all little fibers and constipation (which I hate), not to mention forsaking all the other benefits of vegetables and fruits, seeds and nuts. 

When the theorists sustain a hi-protein diet they should think that not everyone has an insatiable appetite, that the neurological signal of satiety has a purpose, that not everyone carries out brutal gym workouts or hours of daily running. They also forget that protein requirement follows a gaussian law and that some people need much less protein than others (the classic studies of Randd et al).

The problem of sarcopenia is simply solved by working out a little everyday, which will stimulate local IGF-1 (the mechanogrowth factor) and will boost appetite allowing for a natural increase in energy and protein ingestion.

 

[Ron Put]

Well, most people naturally veer toward whatever their confirmation bias may lead them to. If one wants to believe that large amounts of animal protein are good for their health and longevity, there are plenty of "expert" opinion to reassure them. From what I have seen however, and irrespective of my current moral stance, animal protein is generally harmful in the long run compared to whole food plant protein. 

Again, the correlation between muscle mass in an 80 or 90 years old to life expectancy is most likely due to genetics and the ability to maintain muscle mass at such age, rather than looking like Norton at 30.

As often the case with Attia and Patrick, guests may have something to push, Norton is no exception (he pushes supplements and protein shakes).

But I had read an interesting paper discussing "stout" males a while back that sort of made sense, and just found it:

This approach allowed us to eliminate confounding effects of birth cohort, race and place of draft registration on survival. It was found that the ‘stout’ body build (being in the heaviest 15% of population) was negatively associated with survival to age 100 years. Both farming and having large number of children (4+) at age 30 significantly increased the chances of exceptional longevity by 100-200%. The effects of immigration status, marital status, and body height on longevity were less important, 1 and they were statistically insignificant in the studied data set. This study provides the first estimates of height, body build and other vital characteristics for the future centenarians at their young adult ages, and shows that detrimental effects of obesity may have an exceptionally long time range, and that obesity at young adult age (30 years) is predictive for almost three times lower chances of survival to age 100 years.

Edited February 19, 2023 by Ron Put

[corybroo]

23 hours ago, Ron Put said:

But I had read an interesting paper discussing "stout" males a while back that sort of made sense, and just found it:

Thanks for the reference Ron.  The discussion on page 12 made three interesting points:

1) Obesity is bad for longevity.

2) It (body build) was the top variable for predicting longevity.

3) Being slender did not provide a benefit. 

For the last point, I guess it could be argued that there are "good" and "bad" reasons to be slender while there are probably no good reasons to be obese.

Our findings also expand this knowledge further in three ways: 1) the detrimental effects of obesity may have an exceptionally long time range, that is obesity at young adult age (30 years) is still predictive for decreased chances of survival to age 100 years; 2) the significance of body build as predictor of exceptional longevity is much higher than all other potentially important variables, such as body height, immigration status, marital status, and professional occupation (with exception that being a farmer is highly beneficial for attaining exceptional longevity); 3) contrary to expectations based on life extension of calorically restricted animals, a 'slender' body build do not improve chances of survival to 100 years.

 

[BrianA]

New study shows eating more protein actually correlates with worse sarcopenia:

 

Higher dietary protein intake is associated with sarcopenia in older British twins

https://academic.oup.com/ageing/article/52/2/afad018/7036280?login=false

[corybroo]

On 2/18/2023 at 2:58 PM, mccoy said:

I simply find that I'm not able to sustain a hi-protein diet for long.

Isn't this consistent with the discussion we had about the idea of protein leveraging as discussed in Eat like the Animals?  IOW, there's range of protein intake that the organism tries to stay within by either eating more (if short on protein) or eating less (if protein is too high).

BTW, Al has been posting articles by the lead researcher on protein leveraging since 2016.  I just did a search for "Raubenheimer" in these fora and was surprised to see a number of papers already here.   

[mccoy]

Quote

Higher dietary protein intake is associated with sarcopenia in older British twins

https://academic.oup.com/ageing/article/52/2/afad018/7036280?login=false

 

The outcome is definitely contrary to the muscle-centric hypothesis of Dan Layman and others, but we all know that a single paper does not constitute enough evidence of a phenomenon, which may be related to so many causes in a complex system such as the human body. The authors, as usual, do not hint at any possible mechanism. I didn't notice if the cohorts exercised or not, an excess of protein in non-exercising individual aged >60 may trigger some energy deficiency (greater satiety, lesser intake of other nutrients). Also, the authors hint at a possible reverse causation (those with sarcopenia deliberately eating more protein).

Again, the study should be replicated a few times to be considered a real life situation. The authors provide alternative explanations which are then ruled out. I find annoying that in this kind of literature they always underline an association without an in-depth discussion of possible causal mechanisms. The association by the way is not so strong to suggest an acceptable degree of probability of causation (hi-protein causes sarcopenia). I also missed how high is the high protein, I only could see >1.3 g/kg/d, the lower bound may not be enough high.

Quote

It is plausible that this association is due to those individuals with sarcopenia deliberately consuming more protein to ameliorate their muscle loss. Considering sarcopenia is not routinely diagnosed in clinical practice [20], one might consider this unlikely; however, these individuals may have had another event that led to a dietician referral, so it cannot be ruled out. It is worth highlighting that our cohort has a healthy volunteer bias, with a healthier diet and higher protein intake than average, and therefore is distinct from a clinical inpatient or multi-morbid and/or frail population. Thus, our results indicate that for older adults who are relatively ‘healthy’, exceeding recommended protein intake may possibly be more detrimental to muscle health than insufficient protein intake.

 

Edited February 23, 2023 by mccoy

[mccoy]

9 hours ago, corybroo said:

sn't this consistent with the discussion we had about the idea of protein leveraging as discussed in Eat like the Animals?  IOW, there's range of protein intake that the organism tries to stay within by either eating more (if short on protein) or eating less (if protein is too high).

Yes, of course satiation is due to multiple factors beyond protein quantity such as immediate need of energy, fibre/bulk of food, amount of water, type of foods (some inhibit hunger), gastric capacity and so on. But protein definitely triggers a satiety of protein (but not a satiety of sweet foods for example). unless eaten beyond the signal of satiety so that e quasi-nausea intervenes and hunger is neutralized.

Edited February 23, 2023 by mccoy

[CR Curious]

I'm willing to believe that Attia's concern is misplaced, but my understanding is that the relationship between muscle mass and strength is pretty robust and I wonder if the threads Sibiriak referenced (which I looked for and found interesting/insightful) cite enough evidence that we would tend to doubt that maintaining muscle mass in old age will tend to lead to less falls, hip fractures, etc. and that muscle mass earlier in life gives you more of a "cushion" later in life as you start to lose muscle mass as you age (which is inevitable, of course). 

That said, another datapoint here is the stuff about rapamycin. Rapa seems to help maintain muscle mass in old age based on the (albeit limited) evidence I've seen. But the interpretation of the rapa studies I've seen is that it's good, somehow, to suppress mTOR and then turn it on--which would imply that high (animal) protein would be good for health sometimes (when you want to turn mTOR on). Right?

[Todd Allen]

On 2/22/2023 at 3:25 PM, BrianA said:

New study shows eating more protein actually correlates with worse sarcopenia

I'd suggest the correlation of higher protein intake with sarcopenia is not causal and surely confounded by other factors.

At 58 I am able to slowly gain strength and lean mass despite SBMA a genetic muscle wasting disease.  I weigh 130 lbs and after years of careful experimentation with diet closely monitoring body composition and physical performance find my current sweet spot for protein is about 160 grams per day on a diet of roughly 1900 calories.  My tolerance for protein was lower when I suffered from severe insulin resistance and hyperinsulinemia.  I had to sort out other issues like optimizing PH, sleep and strength training to make this work.  This is roughly 1/3 of calories as protein which would be considered high by many although not particularly unusual among body builders.  If it caused sarcopenia you would not find any body builders eating this way.

 

[mccoy]

4 hours ago, Todd Allen said:

If it caused sarcopenia you would not find any body builders eating this way.

Bodybuilders also exercise, many exercise in a brutal fashion and in that article it is not clear if the individuals are exercising or not and how much, and this would constitute a huge confounding factor.

Again, it would seem that that study is to be taken with a huge container of salt, unless some plausible explanation is given.

 

[IgorF]

Hm, the study is about people who are usually not excersising heavily because of age. It is relatively easy to imagine a possible path like:

- abundance of protein triggers some signaling for breakdown+rebuild flow

- intuitively breakdown is easier to be done and less energy eager

- since older people are worse at rebuild part an excess of abundance signaling will shift the overall balance into breakdown

 

So there is probably an optimal range of protein or perhaps rather individual aas where the mechanism will make least harm.

That is a speculation off course..

 

Br,

Igor

 

[Ron Put]

I like twins studies for a number of obvious reasons and I don't find this study's results all that strange.

These are generally healthy subjects in their 70s. I'l try to extrapolate based on my personal experience.

I am just about 60 and generally healthy. I am vegan, consuming between 100-110% protein per day, mostly from legumes and nutritional yeast (it surprised me), according to Cronometer. Since I am vegan, the protein is presumably less absorbable than "high quality" animal protein. I am lean (11.7-13% body fat according to yearly DEX scans and tracked daily by a Withings scale which measures consistency about 1.5% lower.Bone density is still good at 0.5 T-score, especially for my pretty lean body (fat people often have higher bone density). Muscle mass is between 85-86%.

Now about muscle mass. Most men my age I know consume far more protein than I do, often in the form of "high quality protein." While most are shorter than my 6.1 height, most are also beefier. Some stil go to the gym, but my guess is that I am stronger than at least half, and most if measured pound per pound. These days I can do just over 50 decent push-up continuously in about 75 seconds. I don't reay do weight-lifting, just push-ups and pull-ups mostly, and relatively steep hiking on most days.

My long-winded point is that I am at just a tad over RDA for protein intake, but since it's all pant-based protein, it's not al absorbed (my fiber intake is rather robust, often about the same as my protein intake). Yet my muscle mass is steady, without heavy weight workouts. Genes undoubtedly play some role, but that's why I like twins studies.

One other point. Many of the protein studies are sponsored by entities with vested interests selling supplements or by the meat and dairy industry. This does not automatically mean that they are bad studies, but methodology matters, as does reporting of negative or inconclusive outcomes. Over the last few years I have become far more cautious about accepting headlines, and even studies, at face value.

[mccoy]

15 hours ago, Ron Put said:

My long-winded point is that I am at just a tad over RDA for protein intake, but since it's all pant-based protein, it's not al absorbed (my fiber intake is rather robust, often about the same as my protein intake). Yet my muscle mass is steady, without heavy weight workouts. Genes undoubtedly play some role, but that's why I like twins studies.

Ron, your routine exercise is not a trivial one, pullups do provide strong mechanical stress to muscles, even more than weight lifting (I do pullups with a pull machine at the gym and I'm surely loading less than you are). No wonder that your muscle mass is steady, pushups and pullups, I suggest to add dips and that's a complete upper body routine.

For what we know, nutritional yeast may have a hi DIAAS, or mixtures of yeast and legumes. There is no data on that. Also, long-time vegans may become a little ruminant-like, as discussed in another thread, and synthetise essential amino acids from ingested carbon and nitrogen.

 

[mccoy]

In addition to all the above: if we want to try a more detailed analysis of the article, just in the abstract there are some useful hints. Emphasys is mine.

• This is an observational study, prone to many kinds of errors and from starting data which may not be accurate. The GIGO factor may not be negligible here.
• Participants (n = 3,302) were 89% female (n = 2,923), aged a mean of 72.1 (±7.3) years. A very specific subgroup, above all most of them are  post-menopause women. The study is more representative of this group and much less of males.
• Using optimal protein intake as the reference group (1.0–1.3 g/kg/day), there was no significant association between protein intake (neither high nor low) and low muscle strength, or between low protein intake and sarcopenia  in unadjusted models. So the lack of association was in unadjusted models, and the protein intake classes may not be so distinct, there is vagueness about it, at least so far.

[Alex K Chen]

Just get follistatin therapy from Minicircle. They're doing trials now.

We still need *long data* from them, and data on whether they increase benchpress values and not just muscle mass, but they could solve *everything*

https://www.rapamycin.news/t/minicircle-this-biohacking-company-is-using-a-crypto-city-to-test-controversial-gene-therapies-mit-tech-rev/5647

[Ron Put]

I came across an article about the supposedly oldest marathon runner in the world, who gave up marathons at the 100, but still walk 5 miles per day:

The #1 Eating Habit the World's Oldest Male Athlete Follows To Run at 111 (yahoo.com)

On the other hand, there seem to be only two wrestlers to ever cross the 100-year barrier, and the oldest, Abe Coleman, was of relatively small overall mass at just over 5", and died at 101.

Just saying.