Weight gaining while on CR

[mccoy]

My present obsession is to gain muscle weight at the same time keeping off the anabolic, anti-longevity signals of IIS and mTOR. Easier said than done. When much younger and a gym rat, I was able to build conspicuos muscle by eating lots of ricotta cheese, rich in anabolic whey proteins, and eggs. Plus natural carbs like honey, fruit and fruit juice.

 

The above of course would irremediably trigger the main metabolic pathways we know are NOT conducive to longevity. 

 

Now, after having lost much of the former muscle due to forced inactivity, what I'm trying to do (this is an ongoing experiment) is to upregulate mTORC1 in muscle tissues, simply by supplying them with more protein than the minimum required at rest. So I lift weight at 60-70% my maximum load (maximum liftable weight single repetition), trying to stimulate muscle protein synthesis (MPS). Arguably, this is not the same as stimulating growth and reproduction (which would necessarily thwart longevity). Conceptually, we are stimulating the functional requirements of the body, which adapts itself to environmental demands by growing muscle cells, sequestering the excess proteins (amino acids, especially leucine) before they reach organs and other tissues.

 

The above is what I understand at present. I may be wrong, hopefully not too much. The tricky part is to estimate how much additional protein is needed to allow MPS without upregulating IGF-1 and mTOR in non-muscle tissues. 

 

That's tricky before we should estimate first our at-rest minimum proteins requirement, then our additional protein requirement because of exercise. It's a biochemical juggler's work.

 

I'm monitoring my weight, my muscles size and estimating my body fat. Without a DEXA scan it's not easy at all. I might have 24 hours urine analysis done, to ascertain the nitrogen balance. More simply I try to keep proteins as low as possible while allowing some MPS. I'm not using free leucine, only natural foods and I'm following instinct. Istinct often will tell me not to feed the body proteins just after exercise, which is the opposite of what is suggested.  Experience has taught me to heed instinct first. The muscle growth window may not open soon after exercise, whereas it might remain open later and last more days, not just hours. HUNGER is the telltale, especially hunger for proteins, muscle tissue telling you that it's looking forward to provide MPS.

[Todd Allen]

Scroll down on this page to read Dr. Rhonda Patrick's discussion with many references of the effects of heat stress therapy, which includes promoting muscle growth and perhaps longevity even though muscle growth in part comes from boosting GH->IGF1->mTOR.  I added daily hot baths to my regimen in July and believe it contributed to my gaining muscle and performance while rapidly losing weight despite having a degenerative neuromuscular disease that was previously causing rapid muscle wasting and nerve damage.

 

http://fourhourworkweek.com/2014/04/10/saunas-hyperthermic-conditioning-2/

 

and here is a link to her report on the benefits of cold therapy which I also have been doing via cold baths which will hopefully increase in effectiveness as cooler weather lowers the temp of our cold water supply.

 

https://www.foundmyfitness.com/reports/cold-stress.pdf

[GreyCup]

Any update on your progress mccoy? I have similar objectives.

 

Article discussion captures essence, the below did change my nutrition timing around exercise. But I do not come close to the high ranges suggested herein for concerns you have that I share.

 

Nutrient timing revisited: is there a post-exercise anabolic window? | Journal of the International Society of Sports Nutrition | Full Text

 

 

https://jissn.biomedcentral.com/articles/10.1186/1550-2783-10-5

[mccoy]

Hi Greycup, the Aragon & Scheonfiled, 2013 article you cite is a good synthesis, although the current practice in the bodybuilding environment is to err on the safe side, providing isolate whey proteins + a little carbs just after training plus 3 to 4 protein meal per day. BCAAs just before the workout.

 

I discontinued a rigid application of such strategy. It may be suitable when muscles are being very impervious to mass gaining, even by intense training, or in elder people to counteract a state of sarcopenia and give anabolism a boost.

 

I don't know your goals, where you are starting from, at what age and fitness level. My present strategy:

 

To avoid nagging injuries and setbacks, after a very long period of inactivity, instead of going for the suggested 60% max load, I'm practicing what may be called "Low intensity, hi volume, prolonged training".

 

That it, I find a weight I'm confortable with, I make 10-20 repetitions with perfect form with it, I repeat until I total 200-300 repetitions. It takes a long time and I usually carry out chores in between sets. But it seems to work, since muscles do get sore, at the same time minimizing nagging joints and connective tissues problems. 

 

Last time I did 300 reps of front squats with only 15 kg loading but perfect form, deep down, deliberate. The effect was intense and lasted 5 days (sore muscles). Maybe I went a little overboard but muscle soreness usually entails mTOR activation and MPS. The mechanical receptors activating Akt and what I call the 'right hand side' of mTOR are stimulated by either hi loads and few reps and small load and lots of reps.

 

During such Hi volume training I eat watery fruit to get hydrated and to have ready fuel to go on, especially with squats, which can be grueling. This constitutes the first part of my lunch.

 

Just after I'm usually very hungry and will eat digestible proteins such as cultured milk, cottage cheese and so on. Sometimes muesli with soy milk and pea proteins. This constitutes the second part of my lunch.

 

I also do lighter cardio workouts as often as I can.

 

As in our case, when the priority is not competitive fitness and  extreme muscle gain, I believe that it is not at all necessary to follow a rigid feeding timeline.

 

Protein amounts: I find I'm eating lots of protein, since workouts are making me hungry. They are mostly plant based proteins (75% of protein intake), except the dairy stints just after major workouts (2-3 times per week). Last week I averaged 1.6 g kg^-1_LBM d^-1 (95 grams) which is about twice the RDA (or 170% if ideal weight, not LBM is the reference). Also, I averaged 250% Leucine RDA and 235% Methionine. Protein make up 12% of total energy intake.

 

Since I've almost constantly sore muscles, I believe the amminoacids right now are being used to replace the broken down muscle tissue. Until adaptation will set in. 

I'm consciously avoding overamplification of the anti-longevity signals by decreasing animal proteins (more than halved them) and avoiding protein supplementation (except a little pea protein). I also avoid BCAAs and creatine supplements, I only take a limited targeted supplementation of micronutrients.

 

Bottom line: I'm slowly adapting to exercise and growing more muscles. At my present age, 56 and a long time inactive, slow does the trick. Probably, there is no way we can work out with weights and increase muscle tissue at the same time restricting protein. Restriction in this context must be construed as achieving a slightly positive nitrogen balance and not going overboard with it and getting obsessed with protein meals. Also, CR can be practiced, as bodybuilders do, after mass has been gained to get ripped. In such a way restriction may be calibrated to retain the desired mass, alternating gaining periods when necessary.

[GreyCup]

Thanks for the insight. Following your instincts is probably optimal, and this seems like a good strategy. I would be characterize my diet as pesco-vegan, but limited to 10oz of fatty fish (sardine, salmon) per week. I am finding after water fasting and FMD, my weight seems to be resetting lower, which is personally suboptimal even if it is metabolically advantageous, as I would like to maintain BMI of 21. With my various fitness activities, I seem to be net negative on calories many days. I have experimented with low fat hi carb but end up losing too much weight, so now macros run around 10:45:45. I am considering experimenting with hi fat keto vegan type diet, but it may necessitate protein supplements to achieve the 10% target which is also not optimal as I prefer whole foods. Not sure how this approach would impact muscle development and weight stabilization at higher level, but will report back if I do experiment with it.

[mccoy]

Greycup, since you are citing macros, that's another conceptual framework we might pursue.

I have yet to deepen the understanding of the 10% protein  concept which, according to recent literature, is favourable to longevity. Plausibly, that means that, within a range of actual energy requirements, ranging from moderate caloric restriction to higher intake due to exercise, cold exposure and other additional requirements, trying to keep proteins not far from 10% of total calories ensures optimul longevity.

 

The above observations might be due to the fact that nature meant our metabolism to work optimally when the 10% ratio is satisfied. Preferably, satisfied mostly by vegetable proteins.

 

So, if we are more hungry because of more exercise, we increase our caloric intake and increase likewise the protein intake to mantain it at 10%. Conversely when such need for more energy ceases to be. As simple like that.

 

Actually, many vegan athletes just eat more when needed and do not worry at all about protein, which are scattered all around foods.

 

The above would constitute a very elegant and effective solution to our worries; maybe nature just intended us to eat according to hunger and about 10% of protein as an average ratio. This would ensure optimum metabolic efficiency, healthspan and longevity in most conditions.

 

The above is just speculation, which I'm going to further in the other specific thread.

[mccoy]

I have experimented with low fat hi carb but end up losing too much weight, so now macros run around 10:45:45. I am considering experimenting with hi fat keto vegan type diet, but it may necessitate protein supplements to achieve the 10% target which is also not optimal as I prefer whole foods. Not sure how this approach would impact muscle development and weight stabilization at higher level, but will report back if I do experiment with it.

 

I have decreased saturated fats and I too am fatiguing to keep my present weight and BMI of 23. after FMDs the body recovers but often at a lower level.

 

A typical ketogenic diet in athletes is: 20:5:75→ P:C:F, which is a tad higher than the optimal 10% protein.

That would be an interesting experiment but it is used by bodybuilders during the conditioning period, to get shredded and tends to decrease weight, it's probably not going to make you gain mass. Also, natural vegan keto is very hard to pursue, since the most keto-friendly foods: cheese, fish, meat, are not allowed and too many nuts may entail too many carbs, except maybe for macadamias and brazil. I would use pea protein mixed to low carb soy products for example, but I doubt that vegan-keto is a feasible way to go. Also, BCAAs supplements would probably be needed, they are vegan but they are sure not natural.

[Gordo]

I don't personally do or recommend high protein for longevity, but if you are trying to add muscle or weight, you might consider doing what these guys do:

https://youtu.be/fuc7IDQk760

https://youtu.be/WtPGAtah6Fk

 

[Sibiriak]

 

mccoy: ...the Aragon & Scheonfiled, 2013 article you cite is a good synthesis

 

I have Brad Schoenfeld's 2016 book, "Science and Development of Muscle Hypertrophy".   It covers all the basic issues surrounding muscle growth and has tons of references--too many for me to even begin to get into.    Of course,  there are still controversial areas.

 

Here's a summary of his recommendations regarding nutrient timing:

 

 

Practical Applications

 

It is important to consume high-quality protein (at a dose of ~ 0.4 to 0.5 g/ kg of lean body mass) both pre- and postexercise within about 4 to 6 hours of each other depending on meal size. Those who resistance train partially or fully fasted should consume protein (at a dose of ~ 0.4 to 0.5 g/ kg of lean body mass) as quickly as possible postworkout, preferably within 45 minutes of the bout. Those who perform 2-a-day (morning and evening workouts in the same day) should consume carbohydrate (at a dose of ~ 1.0 to 1.5 g/ kg of lean body mass) within 1 hour postworkout.

 

Take-Home Points

 

A positive energy balance is necessary for maximizing the hypertrophic response to resistance training, but overconsumption ultimately is detrimental to gains.

 

Those seeking to maximize hypertrophy should consume at least 1.7 g/ kg/ day of protein. Qualitative factors are not an issue for those eating a meat-based diet. Vegans must be cognizant of combining proteins so that they get sufficient quantities of the full complement of EAAs.

 

Carbohydrate intake should be at least 3 g/ kg/ day to ensure that glycogen stores are fully stocked. Higher carbohydrate intakes may enhance performance and anabolism, but this may be specific to the individual.

 

Dietary fat should comprise the balance of nutrient intake after setting protein and carbohydrate amounts. People should focus on obtaining a majority of fat from unsaturated sources.

 

At least three meals consisting of a minimum of 25 g of high-quality protein should be consumed every 5 to 6 hours to maximize anabolism.

 

Nutrient timing around the exercise bout should be considered in the context of the periworkout period. It seems prudent to consume high-quality protein (at a dose of ~ 0.4 to 0.5 g/ kg of lean body mass) both pre- and postexercise within about 4 to 6 hours of each other depending on meal

 

(Kindle Locations 3205-3220)

[Sibiriak]

From the same book-- a summary of Schoenfeld's recommendations for a hypertrophy-oriented resistance training regime  (the book goes into all the issues in great detail):

 

Take Home Points

 

Multiset protocols favoring high volumes of resistance training optimize the hypertrophic response. As a general guideline, beginners should perform approximately 40 to 70 repetitions per muscle group per session; more advanced lifters may need double this amount. To avoid overtraining, volume should be progressively increased over the course of a training cycle; periods of reduced training volume should be integrated on a regular basis to facilitate the recovery process.

 

Higher training frequencies appear to confer benefits, at least over short-term training protocols. However, split routines allow for a greater volume of work per muscle group per session, potentially enhancing muscular adaptations via the dose– response relationship between volume and hypertrophy. It may be beneficial to periodize frequency over time, altering the number of times a muscle group is trained weekly in accordance with individual response.

 

Training across a wide spectrum of repetition ranges (1 to 20 +) is recommended to ensure the complete development of the whole muscle. There is merit to focusing on a medium-repetition range (6- to 12RM) and devoting specific training cycles to lower- and higher-repetition training.

 

Once facility has been established with the basic movement patterns, a variety of exercises should be employed over the course of a periodized training program to maximize whole-body muscle hypertrophy. This should include the liberal use of free-form (i.e., free weights and cables) and machine-based exercises. Similarly, both multi- and single-joint exercises should be included in a hypertrophy-specific routine to maximize muscular growth.

 

Both concentric and eccentric actions should be incorporated during training. Evidence of the benefits of combining isometric actions with dynamic actions is lacking at this time. The addition of supramaximal eccentric loading may enhance the hypertrophic response.

 

An optimal rest interval for hypertrophy training does not appear to exist. Research indicates that resting at least 2 minutes between sets provides a hypertrophic advantage over resting for shorter periods. Including training cycles that limit rest periods to 60 to 90 seconds may allow a lifter to take advantage of any additive effects of metabolic stress, if they exist.

 

Current evidence suggests little difference in muscle hypertrophy when training with isotonic repetition durations ranging from 0.5 to 6 seconds to muscular failure. Thus, it would seem that a fairly wide range of repetition durations can be employed if the primary goal is to maximize muscle growth. Training at very slow volitional durations (> 10 sec per repetition) appears to be suboptimal for increasing muscle size and thus should be avoided. Combining repetition durations could conceivably enhance the hypertrophic response to resistance training.

 

 Evidence indicates a hypertrophic benefit for muscles worked first in a resistance training bout. Therefore, lagging muscles should be trained earlier in the session.

 

Full ROM movements should form the basis of a hypertrophy-oriented program. Integrating some partial-range movements may enhance hypertrophy.

 

 Hypertrophy-oriented programs should include sets taken to muscular failure as well as those that are terminated short of an all-out effort. The use of failure training should be periodized to maximize muscular adaptations while avoiding an overtrained state.   (Kindle Locations 1949-1968).

[mccoy]

 

 

The use of failure training should be periodized to maximize muscular adaptations while avoiding an overtrained state.  

 

That's what I should be careful to right now, sometimes I overtrain but when you like strenuos exercise it is hard to stop before total exhaustion

[Sibiriak]

Mccoy,

 

I used to do some hypertrophy-oriented exercise, but I've given up on it.    I'm  still fascinated by the subject-- resistance training more broadly understood.

 

I started out reading books like  "Science and Practice of Strength Training"**  by Zatsiorsky,  "Supertraining" by Yuri Verkhoshansky/ Mel Siff  and similar.  I recently read Schoenfeld and some others to update myself a bit on the theory.

 

**PDF:

http://www.traininginparadise.eu/wp-content/uploads/Science-and-Practice-of-Strenght-Training-Vladimir-M.-Zatsiorsky-.pdf

 

Nowdays I just do some fairly unsystematic "functional" training--  using homemade devices like junk-filled duffel bags (instead of sandbags);  or snow shoveling--combining resistance training w/ Siberian cold exposure!  And I use some stretch chords to do various dry land swimming exercises to stay swim-fit.

 

Russian functional strength:

https://cdn.liveleak.com/80281E/s/s/20/media20/2013/Apr/6/LiveLeak-dot-com-ac18fa8fedcb-russian_man_lifts_stuck_car.mp4.h264_720p.mp4?-f00KbSBN3-fiGxKEhGseLekzZG2BHTG2hH8nIrDuZRoDculYAkM0r1JNHo8jm9l&ec_rate=499

[mccoy]

Sibiriak, strenght really is a fascinating subject, I wish I had the time to study it in detail and the ability to practice it!

 

I used to have a fixation on strenght when at the gym, although I'm not genetically strong. I'm more of an easy gainer than a strong man, but by lifting heavier weights I grew relatively strong. Lifting without proper supervision though caused me back aches, moreover I developed chronic abdominal pain due to previous surgery, so I had to stop. Maybe I was lucky, since without the abdominal pain I might have compromised my back.

 

Now I'm practically in rehab, a couple of years ago I had bilateral hynguinal hernias. One I operated, the other is a small one and I I can train with it. The interesting fact is that such an hernya removed the chronical pain which doctors had no clue about. So now I'm trying to do my best to regain some fitness and that's a new type of challenge, an interesting one.

 

I'm probably going to order the Schoenfield book, very interesting one, together with the Zatsiorski handbook.

[mccoy]

 

I don't personally do or recommend high protein for longevity, but if you are trying to add muscle or weight, you might consider doing what these guys do:

 

 

Gordo, I saw the vids with Jon Venus, interesting stuff, those guys do show that it is possible to beef up with a plant based diet, although even the largest guys look puny compared to non vegan bodybuilders. On the other hand, the non-vegans and especially the competitive ones use androgens and many other drugs, so a direct comparison is not possible. That's a messed-up sport, the one where you are allowed to take any drugs. The competitors are practically compelled to use otherwise they inevitably will lag behind.

 

Natural bodybuilding is more genuine and vegan bodybuilding is a further challenge. I have this gut feeling (partly confirmed by empirical observation) that a vegan diet is very good for endurance sports, marathons and ultra-marathons, whereas is not ideal for strength sports (with very few exceptions, like Patrick Baboumian and Kendrick Farris). Something in the animal-derived food which is missing in plant-based food, beyond the mere EAAs.

 

Some people do get good results though, and it is anyway fair to compare vegan bodybuilders among themselves. If I were in real shape I think I would try that out as well, I do like those kind of challenges. In the eighties I remember there were absolutely no vegan bodybuilders, Andreas Caling claimed to be a raw vegan but he  himself admitted to eat 10 eggs a day when bulking.

[mccoy]

Greycup, since you are citing macros, that's another conceptual framework we might pursue.

I have yet to deepen the understanding of the 10% protein  concept which, according to recent literature, is favourable to longevity. Plausibly, that means that, within a range of actual energy requirements, ranging from moderate caloric restriction to higher intake due to exercise, cold exposure and other additional requirements, trying to keep proteins not far from 10% of total calories ensures optimul longevity.

The above observations might be due to the fact that nature meant our metabolism to work optimally when the 10% ratio is satisfied. Preferably, satisfied mostly by vegetable proteins.

So, if we are more hungry because of more exercise, we increase our caloric intake and increase likewise the protein intake to mantain it at 10%. Conversely when such need for more energy ceases to be. As simple like that.

 

I'm quoting myself because I have to correct the above. re-reading the articles, I realized that the 10% ratio is relative to carbs, so, relative to total energy, protein woudl be too little (pls look up the other thread on nutritional geometry).

That's one unrealistic thing when working out.

 

I'm going to propose a feasible strategy, and the most practical thing is to start from protein, afterwards adjusting carbs and fats ratios.

[GreyCup]

Lots of interesting content here, thanks to all for the ideas. I prefer to exercise fasted, feel better/stronger, but worried about going catabolic. So, will experiment with 10 grams of hip protein in a beet juice prior to workout, otherwise fasted. Can't bring myself to consume the .4g/kg recommendations seems to high and in opposition to longevity goals. Will have large protein meal within 1 hour of weight training. I also add on sauna to end of sessions for heat stress.

 

timely:

 

https://www.nytimes.com/2017/04/26/well/move/the-best-thing-to-eat-before-a-workout-maybe-nothing-at-all.html?smid=tw-share&referer=https://t.co/ajEPjVnKGd&_r=0

- discusses benefits of walking while fasted and extrapolations 

 

and just came across somewhat related to performance

https://nutritionfacts.org/video/preserving-athlete-immunity-with-chlorella-2/

- some chlorella and nutritional yeast to support immune function around sessions 

[Sibiriak]

 mccoy: I find a weight I'm confortable with, I make 10-20 repetitions with perfect form with it, I repeat until I total 200-300 repetitions. It takes a long time and I usually carry out chores in between sets. But it seems to work, since muscles do get sore, at the same time minimizing nagging joints and connective tissues problems. 

 

Last time I did 300 reps of front squats with only 15 kg loading but perfect form, deep down, deliberate. The effect was intense and lasted 5 days (sore muscles). Maybe I went a little overboard but muscle soreness usually entails mTOR activation and MPS.

 

 

 

That brought to mind the notion of “San Gong”:

 

Wai Dan Muscle/ Tendon tension and relaxation practice focuses on training the Qi in the limbs. The main purpose of increasing the Qi in the limbs is to energize the muscles to their highest efficiency. The specific postures also train the coordination of the muscles in the torso with those in the limbs. If you understand that one of the major purposes of Da Mo’s Wai Dan exercises is to increase martial power, then you will see why the limbs are emphasized in the training. After Da Mo, many sets were created from the same theory, mostly by martial artists.Naturally, these exercises will also improve health. However, many martial artists who trained the Da Mo Wai Dan exercises heavily for a long time found that they over-developed their muscles the way weight-lifters often do.

Although they were healthy as long as they were able to practice, once they got old their muscles degenerated much faster than normal. This is called “San Gong” (energy dispersion). Because of this, Da Mo created a set of Nei Dan exercises which is also included in the Muscle/ Tendon Changing Classic. This set builds up and circulates the Qi internally, preventing the Qi channels from plugging up when the practitioner gets older.

 

Since the 6th century, many martial styles have been created which were based on Qigong theory. They can be roughly divided into external and internal styles. The external styles emphasize building Qi in the limbs to coordinate with the physical martial techniques. They follow the theory of Wai Dan (external elixir, ) Qigong. In Wai Dan Qigong, Qi is usually generated in the limbs through special exercises. The concentrated mind is used during the exercises to energize the Qi. This increases muscular strength significantly, and therefore increases the effectiveness of the martial techniques. Qigong can also be used to train the body to resist punches and kicks. In this training, Qi is led to energize the skin and the muscles, enabling them to resist a blow without injury. This training is commonly called “Iron Shirt” (Tie Bu Shan) or “Golden Bell Cover” (Jin Zhong Zhao). The martial styles which use Wai Dan Qigong training are normally called external styles (Wai Gong) or hard styles (Ying Gong). Shaolin Gongfu is a typical example of a style which uses Wai Dan martial Qigong.

 

Although Wai Dan Qigong can help the martial artist increase his power, there is a disadvantage. Because Wai Dan Qigong emphasizes training the external muscles, it can cause overdevelopment. This can cause a problem called “energy dispersion” (San Gong) when the practitioner gets older. In order to remedy this, when an external martial artist reaches a high level of external Qigong training he will start training internal Qigong, which specializes in curing the energy dispersion problem. That is why it is said “Shaolin Gongfu from external to internal.”

 

Internal Martial Qigong is based on the theory of Nei Dan (internal elixir, ). In this method, Qi is generated in the body instead of the limbs, and this Qi is then led to the limbs to increase power. In order to lead Qi to the limbs, the techniques must be soft and muscle usage must be kept to a minimum.

 

Yang, Jwing-Ming. The Root of Chinese Qigong    Second Edition.

[mccoy]

Sibiriak, since when I'm listening or watching to Rhonda Patrick and the likes, I'm seeing those teachings in a new light.

 

Rhonda says that meditating on a gene may express it.  Meditating on the life force in the muscles may upregulate mTOR in those muscles. Or mithocondria.

 

I remember once I read an interview to the bodybuilder Lee Haney, former mr. Olympia 8 times in a row in the eighties. He recounted that his weak point was biceps, no matter what he couldn't make them grow up to par to the other muscles. 

He eventually overcame the problem by visualization exercises. He just visualized with concentration his biceps growing and growing. 

 

That's an example on how he was able to stimulate mTOR in those specific muscle groups by mental concentration (plus adequate exercise of course). Maybe Rhonda Patrick came across that same interview as well, but I doubt it, that some independent source, although I didn't try to do a literature search.

[Sibiriak]

mccoy: My present obsession is to gain muscle weight at the same time keeping off the anabolic, anti-longevity signals of IIS and mTOR. Easier said than done.    [...] after having lost much of the former muscle due to forced inactivity, what I'm trying to do (this is an ongoing experiment) is to upregulate mTORC1 in muscle tissues ....

 

 

I'm not sure to what extent you are incorporating cold exposure (CE) into your regime,  but I was re-reading the mammoth "Cold Exposure" thread and this post by Dean Pomerleau caught my attention in relation to your concerns:

------------------------------------

https://www.crsociety.org/topic/11488-cold-exposure-other-mild-stressors-for-increased-health-longevity/page-9        #161

 

Dean Pomerleau: 

 

[...]The mystery I'm alluding to is the following: The primary metabolic responses found to accompany cold exposure are all quite anabolic in nature - involving the genesis of new BAT cells, the conversion of WAT cells to BAT cells by adding mitochondria and other cellular machinery to the WAT cells, the biosynthesis of new mitochondria in muscle cells to support thermogenesis in muscles, generating new immune system cells or creating new bone cells. Sure there may be sufficient calories available to support such anabolic activities (at least if you don't starve subjects on top of cold exposure like the Ikeno et al study discussed here). But triggering and orchestrating such anabolic activities is typically done through elevated insulin, IGF-1 and other growth factors. But cold exposure doesn't raise insulin or IGF-1, as discussed here, here, here and here. For example, [2] (discussed in detail here) found serum insulin levels were lower in mice exposed to 17 °C compared with normal room temperature, and insulin was even lower when cold exposure was combined with capsaicin. Study [3] found that IGF-1 was reduced in primates as a result of cold exposure.

 

So the mystery is how the body manages to build up these new tissues and cellular organelles without much in the way of circulating growth-promoting signalling molecules insulin and IGF-1, which are normally required to trigger this sort of biosynthesis, and which are thought to be deleterious to health and longevity. Put another way, how is it that CE seems to be able to mimic CR's beneficial effect of keeping insulin and IGF-1 low (and thereby promoting longevity), while still promoting maintenance & growth of important body tissues like bones and immune cells, rather than catabolizing them the way CR does?

 

This new study [1] (press release), sent to me by a shy CR veteran who I'm hoping will join these discussions, may suggest an answer. The paper is pretty dense, but the upshot can be summarized pretty succinctly. It found that catecholamines, like the noradrenaline released as a result of cold exposure, upregulate the conversion of white adipose tissue (WAT) to brown adipose tissue (BAT) via a pathway that includes PKA (protein Kinase A) increasing mTORC1 (mammalian target of rapamycin complex 1) activity, which in turn pulls the strings to promote BAT synthesis.

 

Did you say mTORC1? Isn't that the same as mTOR? Doesn't CR turns off mTOR as an important part of how it shifts the body from "growth and reproduction" mode to "maintenance & repair" mode? 

 

Yes! And that's where I think things get interesting...

 

Rather than activating MTOR/MTORC1 via the usual pathway, namely Insulin/IGF-1 → AKT → mTORC1, epinephrine (i.e. cold exposure), activates MTORC1 via the pathway Epinephrine → PKA → mTORC1. And this makes a big difference. You see, mTORC1 is a "complex" of proteins (hence the 'C' in its name). It's basically a core mTOR protein with little extra bits hanging off it. Together, these parts form a complex mini-factory, which the authors of [1] liken to a multi-function printer:

 

 Imagine mTORC1 is a machine with multiple capabilities, like a printer/copier/scanner. Energy-storage signaling [via Insulin/IGF1 pathway - DP] pushes one set of buttons and gets one outcome (fat storage), while PKA pushes another set to get a different outcome (conversion to brown fat).

 

In a nutshell, cold exposure programs that anabolic mTORC1 mini-factory in a way that causes it to churn out a different set of outputs & outcomes than if it is programmed by elevated Insulin/IGF-1, with beneficial results (i.e. turning WAT to BAT rather than synthesizing more WAT).

 

This result got my thinking about the relationship between CR & CE, and the possibility of synergy between them. If you haven't already, now would be a good time to (re)read the introductory post from yesterday that serves as a prelude to what I'm going to discuss next.

 

The discussion from here out can best be understood in reference to the three-panel diagram below. It represents three different metabolic milieus - CR only (left), CE only (middle) and CR + CE (right). It is a greatly simplified diagram of important metabolic pathways that I've synthesized based on several diagrams from review papers. I won't claim it is entirely complete or accurate. I'm sure Michael or Al might quibble over the details. But I've tried to highlight as best I can some of the most important pathways involved in the health & longevity benefits of CR and CE based on the available science, in a way I hope is comprehensible. 

 

Let's start with the "CR Only" metabolic milieu illustrated on the left:

 

 

The green-shaded regions represent pathways that are upregulated by CR, while the red regions show pathways that CR downregulates. First, we all know the CR upregulates the beneficial AMPK / SIRT1 / FOXO pathway(s), with pretty much unmitigated benefits in terms of insulin sensitivity, stress resistance and overall longevity goodness.

 

The red region is more interesting - due to its "double-edged sword" nature. It shows that by keeping insulin and IGF-1 low, CR does lots of good things, including improving insulin sensitivity, reducing systemic inflammation and in general slowing the accumulation of age-related damage. At the same time, it turns the mTOR / mTORC1 activity down/off. This has some good effects, like preventing accumulation of WAT and enabling autophagy (killing off) of rogue cells. But turning off mTORC1 has its downsides as well. In particular, mTORC1 is responsible for orchestrating many important anabolic processes, beyond just the browning of white fat talked about in [1]. For example, mTORC1 is important for promoting the growth of new bone cells [4], for differentiating/activating new lymphocytes in the immune system [5], including natural killer (NK) cells [6], which are particularly important for fighting cancer as discussed in a post on this thread a few days ago. Further, mTOR is critical for adult neurogenesis and hence maintaining a healthy brain [7]. Unfortunately I left off "Brain Cell Synthesis" from the bottom row of outcomes in the above diagrams, so you'll have to use your imagination☺. The other key benefit of mTOR activity I left off the diagram is protein synthesis to build and preserve skeletal muscles [8]. 

 

In short, by dramatically attenuating Insulin / IGF-1 signalling, CR prevents lots of bad health & longevity consequences, but also shuts down important anabolic activities like synthesizing BAT, bone, immune, muscle and brain cells. This is why many thoughtful CR practitioners harbor some concerns about the long term effects of CR on bone health, immunocompetence, muscle loss and cognition. In fact, there have been endless discussions on these forums (like this recent one) and on the email list before that about the possible downsides of very low IGF-1 resulting from serious CR, usually focused on concerns about bones, brains and/or brawn☺. 

 

Now let's look at the middle panel above, representing the metabolic milieu resulting from cold exposure without calorie restriction - i.e. eating enough calorie to fully compensate for the extra thermogenesis required, so as to maintain the same (unhealthy) weight as someone eating ad lib. As you can see, to first approximation, things are green (activated) across the board. But activating SIRT1 and AMPK via adiponectin, CE upregulates the same longevity pathway as CR - a good thing. But at the same time, with an excess of calories coming from eating completely ad lib, the Insulin/IGF-1 pathway gets fully activated, and mTOR gets an extra boost from the PKA pathway discussed in [1]. So you get the detrimental, pro-aging effects of Insulin / IGF-1 (systemic inflammation, etc.) along with the mixed blessing of the full complement of anabolic effects of mTOR activation (include white fat synthesis & obesity). As a result, cold exposure combined with an ad lib diet (e.g. Ikeno et al's "cold but chubby" control mice, discussed here), doesn't improve health or longevity relative to warm, ad lib fed controls. In other words, cold ad lib rodents eat a lot more, maintain the same weight, and live as long as, but not longer than, warm ad lib controls.

 

By now you may see where I'm going with this. But if not, take a look at the third panel above, representing the metabolic milieu resulting from the combination of CR & CE. As you can see, CR [ and/or protein/ BCAA restriction--Sibiriak]  keeps Insulin & IGF-1 low, preventing their detrimental, pro-aging effects. But at the same time, CE does an "end run" around the Insulin/IGF-1 → AKT → mTOR pathway, instead activating mTOR via the "back door" PKA pathway. Activated in this way, mTOR helps promote growth of important new cells, but in different combination than if activated via the insulin/IGF-1 pathway (e.g. promoting BAT rather than WAT). As a result, the combination of CR + CE provides the anabolic bone, brain and immunity [and muscle preservation/growth--Sibiriak]  benefits of mTOR activity, without the downsides associated with elevated insulin and IGF-1. 

 

In short, the combination of CR & CE appears to allow you to have your cake and eat it too.

 

[red highlighting added]

[mccoy]

Sibiriak, Dean has indeed done a formidable job of pointing out all effects of CE on cellular metabolism. Actually, during a google search I came across his 3rd diagram (CE+CR) and commented it in one of the more recent threads. But what is of interest here, and what I understood of mTORC1 activation, which also serves to develop Dean's discussion further, is that specific tissues have specific receptors which start a signaling cascade which eventually upregulates mTOR. So, apparently, each tissue/organ (or at least, some of them) have their specific 'favorite' signal.

 

For example, mTOR in muscle cells is sure activated by the common (to all tissues) pathways: Leucine→RAGulators + [iGF-1+Insuline]→ PI3k→akt.

 

However, this is true up until a baseline. Abundant nutrition will make your muscles grow until your genetic baseline (dependent upon many factor among which the myostatine pathway). You cannot grow bodybuilders' muscles by providing abundant Leucine, aminoacids and glucose alone. After that baseline, you need the specific signal of the mechanoreceptors, which boost the PI3k→akt pathway to higher levels than growth factors alone. As a matter of fact, this pathway seems to supersede the growth factors pathway.

 

Likewise, in the case of brown fat, we cannot think that increasing the amminoacids and glucose intake will increase BAT tissues. This is true up until a genetic baseline. To make BAT tissue increase, we need to activate its specific pathway by the norepinephrin receptors:

 

1)COLD→beta-adrenergic stimulation→PKA→mTORC1

 

2)COLD→sympathetic nervous system→Akt→mTORC1 (also →mTORC2→Akt→mTORC1)

 

The complete discussion is in the CE thread, (Posted 11 February 2017 - 11:33 PM)

 

So, CE only does not upregulate mTOR in muscles, since muscles do not have NE (norepinephrine)receptors upstream the mTOR pathway, rather they are sensitive to mechanoreceptors, whereas mTOR in BAT is not sensitive to mechanical loading, but it is sensitive to the NE signal.

 

Now, brain cells and cells of the nervous system might have some specific receptors which supersedes the IGF1-Insuline→PI3K→Akt  pathway, but I don't know if and which ones. This seems to be a common feature though of many bodily tissues:

 

1. Baseline mTOR activity: regulated by the common (to all organs) pathways
2. Specific mTOR upregulation: regulated for every single organ/tissues by specific receptors.

 

For example, upregulation of mTOR in the immune system to increase lymphocite size and quantity might be triggered by some 'stress sensor' which is sensitive to the hormetic signals we all know. This is just an hypothesis, but a reasonable one. And I already posted an article on piperine in black pepper stymulting mTOr in the intestinal immune system. And we all know that bone tissue is created by mechanically stressing the bones, similarly to the mechanical stress of skeletal muscle tissue, although probably in a slightly different way.

 

 

Bottom line, CE probably will not upregulate mTOR in skeletal muscles directly, whereas may contribute to upregulate it by increasing appetite, increasing NE which increases willingness to engage in physical activity, and so on....

 

Another interesting aspect: CR might chronically downregulate mTOR in the immune system, making practitioners more vulnerable to disease, but we might bypass such problem by providing an hormetic stymulus which will activate the PIK3→Akt pathway in the same immune system, regardless of CR. Consequently, mTOR activity will get a boost providing of course that there is a basic Leucine signal + amminoacid availability.

[Sibiriak]

Mccoy :... strenght really is a fascinating subject, I wish I had the time to study it in detail and the ability to practice it!

 

I think it's important to keep in mind that as we grow older  what really matters is the loss of functional ability brought about by the loss of strength, power, agility, balance, coordination,  flexibility etc.  The loss of muscle mass is involved in that, of course,  but strength and power, for example,  are not strictly determined by muscle mass,  and resistance training (including neuromuscular training) for functional strength /power uses  different methods than resistance training  strictly for muscle hypertrophy.

 

Consider:

 

Longitudinal Muscle Strength Changes in Older Adults: Influence of Muscle Mass, Physical Activity, and Health (Hughes et al.)

https://academic.oup.com/biomedgerontology/article/56/5/B209/554584/Longitudinal-Muscle-Strength-Changes-in-Older

 

The total amount of muscle is a major determinant of the force-generating capacity of the muscle, as demonstrated by the high correlation between muscle mass and strength in a cross-sectional analysis ⁽⁴⁾. This has led some to conclude that the loss in muscle strength is due entirely to the loss in muscle mass ⁽³⁰⁾. However, a significant association between the change in muscle strength and mass with exercise training or restricted activity is rarely observed ^(31)(32).

 

This, along with the finding of disproportionately greater loss of strength compared to lean tissue declines over 11 to 15 years and no correlation between muscle strength and fiber area changes ^(7)(10), suggests that other neuromuscular changes may mediate muscle strength change.

 

In our cohort, muscle mass changes explained a small (5%) part of the variance in knee strength.

 

 

 

Conclusions

The results of this study quantify the substantial longitudinal decline in maximal dynamic force production of upper and lower extremity muscle groups. Although strength is expected to decline in these older subjects, many individuals increased strength over the follow-up period, pointing to the potential to modify muscle function by exercise or through accretion of lean tissue with age. Older subjects in general had greater relative losses in leg strength than younger subjects in our cohort. Muscle mass changes accounted for 5% of the change in strength. In men, a change in health status predicted muscle strength declines. Because only a small amount of the variance in strength was explained by muscle mass loss and because of the lack of association with physical activity, there is a need to explore the relative contribution of other cellular, neural, or metabolic mediators of changes in muscle function.

 

 

The Loss of Skeletal Muscle Strength, Mass, and Quality in Older Adults: The Health, Aging and Body Composition Study

https://academic.oup.com/biomedgerontology/article/61/10/1059/600461/The-Loss-of-Skeletal-Muscle-Strength-Mass-and

 

Conclusions. Although the loss of muscle mass is associated with the decline in strength in older adults, this strength decline is much more rapid than the concomitant loss of muscle mass, suggesting a decline in muscle quality. Moreover, maintaining or gaining muscle mass does not prevent aging-associated declines in muscle strength.'

 

Muscle weakness is consistently reported as an independent risk factor for high mortality in older adults (1–5). Since muscle strength also appears to be a critical component in maintaining physical function, mobility, and vitality in old age, it is paramount to identify factors that contribute to the loss of strength in elderly persons. Sarcopenia, the age-associated loss of skeletal muscle mass (6–10), has been postulated to be a major factor in the strength decline with aging (9–11). Moreover, sarcopenia is related to functional impairment (12,13), disability (14,15), falls (16), and loss of independence (17) in older adults. However, the prospective association between changes in muscle mass and changes in strength has not been extensively evaluated in older adults.

 

 

A primary finding of this study was that initially well-functioning older men and women exhibited a 3-fold greater loss in strength than decline in muscle mass over the course of 3 years of follow-up. This pattern was consistent for men and women and for blacks and whites. Another novel finding was that maintenance or even gain of lean mass in these older men and women did not necessarily prevent the loss of strength. Thus, while these data do not diminish the importance of maintaining muscle mass with old age, they do underscore the importance of muscle quality in older adults.

 

 

Although it has been postulated that reduced muscle mass plays a major role in the age-related decline of strength (9,32,33), in this large cohort of older adults, initial lean mass and changes of lean mass could explain only a small portion (∼5%) of variability of strength decline. Moreover, even individuals who maintained their lean mass became weaker, and individuals gained weight and lean mass did not become stronger as might have been expected. This finding further suggests that alterations in muscle quality play a role in the loss of strength in old age. Hughes and colleagues (29) also reported that changes in muscle mass explained only 5% of the changes in strength.

There are additional interpretations of the association between age-related loss of muscle mass and strength. It is possible that muscle weakness leads to decreased function, diminished physical activity, and sometimes immobility, consequently leading to secondary muscular disuse atrophy. Thus, decreased muscle mass is likely both the result and the cause of the age-related loss of strength. Both the selective loss of type 2 muscle fibers (37) and increased levels of proinflammatory cytokines (38) have been postulated to be related to the loss of strength with aging.

 

Moreover, exercise-induced increases in strength are typically greater than would be expected for the concomitant increase in muscle mass (39), although this dissociation between changes in strength and mass has recently been challenged in studies examining changes in both the strength and size of single muscle cells (40).

 

Thus, it is possible that age-related neurological changes, the hormonal and metabolic milieu, pro-inflammatory cytokines, and perhaps fat infiltration—lipotoxicity—may contribute to progressive muscle weakness in older adults. Further studies are needed to help elucidate how these factors may be related to changes in muscle mass and strength with aging.