Exercise improves health by evoking 'recycling'

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RRM
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Re: Exercise improves health by evoking 'recycling'

Postby RRM » Wed 27 Feb 2013 11:31

RRM wrote:Autophagic proteolysis and sirtuin activity are downregulated by the insulin signaling pathway.
So low insulin sensitivity may be a factor in inhibiting autophagy right ?
Yes, and insulin resistance (beta cell organelle dysfunction) is associated with deficient autophagy Full Free Article
There are 'anomalies' in autophagy responses in (type 1 and 2) diabetes. Mellor KM et al
Defective autophagy causes insulin resistance Full Free Article
Hence caloric restriction and exercise (both catabolic) evoke autophagy.
What sort of exercise ? Aerobic exercise ? Anaerobic exercise ? Is walking also evoking autophagy ?
Both acute and chronic. Both aerobic and anaerobic. From the various studies i read, it may be hours of walking or short bursts of intense activity,
and anything in between.
Example: During 80 minutes, mice either had to run 900 meters or at 75% of maximum runnning capacty. Full Free Article
The only thing that is essential, is the induction of low levels of energy (AMP to ATP) in muscle cells,Hardie DG
induced by both exercise and caloric restriction Full Free Article,
which can also be achieved by walking.

I created a preliminary Wai Wiki page for autophagy
http://www.waiwiki.org/index.php/Autophagy
Of course, i still need to add a lot of info.
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vitamin D/autophagy

Postby Kasper » Thu 28 Feb 2013 09:00

We show that 1,25-dihydroxyvitamin D3 (1,25D3), the active form of vitamin D, induced autophagy in human monocytes via cathelicidin, which activated transcription of the autophagy-related genes Beclin-1 and Atg5. 1,25D3 also induced the colocalization of mycobacterial phagosomes with autophagosomes in human macrophages in a cathelicidin-dependent manner. Furthermore, the antimycobacterial activity in human macrophages mediated by physiological levels of 1,25D3 required autophagy and cathelicidin. These results indicate that human cathelicidin, a protein that has direct antimicrobial activity, also serves as a mediator of vitamin D3-induced autophagy.
http://www.ncbi.nlm.nih.gov/pubmed/19748465
http://www.apo-sys.eu/aposys/Publicatio ... ophagy.pdf
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autophagy inhibitors

Postby Kasper » Thu 28 Feb 2013 09:20

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Autophagy

Postby RRM » Thu 28 Feb 2013 14:42

From Autophagy fights disease through cellular self-digestion (full free article)
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Re: Methionine restriction

Postby RRM » Wed 13 Mar 2013 17:54

Added Dime's methionine restriction thread to this autophagy thread (see first 2 posts of this thread).
In addition:
RRM wrote:
dime wrote:Methionione restriction in the diet seems to increase lifespan
methionine is the main regulator of step-down proteolysis, a process generally connected with autophagy Grinde B et al
"protein catabolism in skeletal muscle of healthy subjects may be sensitive to amino acids ("the 'regulatory amino acids'", including methionine) which reportedly regulate autophagy and such amino acid-sensitive mechanism of protein catabolism may be disturbed in cancer patients" Holm E et al

"Methionine restriction (MetR) decreases the protein biosynthesis rate due to methionine limitation, which correspondingly decreases generation of ribosomal-mediated error proteins, which then lowers the total abnormal protein load that cellular proteases and chaperone proteins (mitochondrial and cytoplasmic) must deal with. This will increase protease availability for elimination of proteins damaged postsynthetically and help delay abnormal protein accumulation, the major molecular symptom of aging. ... MetR will also increase lysosomal proteolysis, including autophagy of dysfunctional mitochondria, and promote mitogenesis. Hipkiss AR
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Re: Exercise improves health by evoking 'recycling'

Postby panacea » Tue 19 Mar 2013 08:41

Even better than walking, in my opinion, is to find a way to be on your feet (but not standing completely still) for as much of your ordinary routine/day as possible, and take frequent cold showers, sleep and live in a slightly colder temperature house/office if you can manage it, etc.. that way you don't have to exercise as much as the next person in order to expend the same amount of energy, and it will be energy lost in the most balanced way possible.
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Re: Exercise improves health by evoking 'recycling'

Postby RRM » Tue 19 Mar 2013 15:25

panacea wrote:that way you don't have to exercise as much as the next person in order to expend the same amount of energy, and it will be energy lost in the most balanced way possible.
I dont think its the total amount of energy used that correlates with autophagy.
Autophagy is triggered by a local or overall (temporary) lack of energy or amino acids.
Exercise may induce a lack of energy in cells, evoking autophagy.
Caloric restriction (and intermittent fasting) may (temporarily) evoke autophagy by reducing the supply of energy to cells.
Low protein diets (as in the Wai diet - acne sample diet) may evoke autophagy by reducing availability of amino acids to cells.
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Re: Exercise improves health by evoking 'recycling'

Postby panacea » Tue 19 Mar 2013 23:35

It's important to remember that standing as opposed to lying down or sitting for long periods each day, week after week, year after year, could end up expending more energy than even walking for an hour or two each day and sitting in a cubicle instead of standing at a work desk.

I don't subscribe to caloric restriction,
http://www.nature.com/news/calorie-rest ... un-1.11297

I deduce from logical thinking that there must be a sweet spot - where nutrient needs are met optimally from high quality, nutrient dense foods, in the correct timing and amounts, to allow for self repair/recycling tasks alongside digestion. I also realize there are countless factors which aide in health/longevity outside of diet and exercise, such as our posture. In a standing posture, our body is better designed to digest things, mechanically, in relation to the design of our organs and gravity, than sitting a C shape hunched over a desk.

I propose that it's due to removing an excess of food and/or poor quality food. The world has yet to learn optimal food habits, until it does, we can't trust the research based on removing this poor quality food from animals/humans or other living things to mean anything other than lifting a burden from cells and enhancing their performance because of it.
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Re: Exercise improves health by evoking 'recycling'

Postby RRM » Wed 20 Mar 2013 13:52

panacea wrote:I propose that it's due to removing an excess of food and/or poor quality food.
Initially, i was sceptic too (about the effects of caloric restriction and exercise), but i was convinced by the simple logic involved in autophagy,
and by the loads of solid evidence that supports the autophagy-longevity theory.
Aging is associated with the accumulation of damaged, malfunctioning and redundant proteins in our cells.
Autophagy is a survival mode, responding to a lack of protein / energy in cells.
Autophagy is the process of cleaning up these proteins, using them for energy and (re)construction,
instead of obtaining the required proteins from diet.
By stressing cells, one triggers this clean up process, preventing cell death due to accumulation,
and making protein synthesis more efficient.
Hence the bonus of increased cell survival, increasing longevity. (autophagy replacing apoptosis)

Basically, without elevated autophagy, there are a lot more dysfunctioning cells that need to be destroyed and rebuild completely.
With elevated autophagy, dysfunctioning parts and accumulating waste products are being recycled in the cell.
so that the entire cell is saved.
Autophagy is like maintenance, instead of buying a new car in case of a puncture, or every time the windows will not close.
This saves a lot of energy and protein.
Hence the possibility of caloric restriction; the additional energy (up to 40%) is saved by precise maintenance and recycling instead of whole-cell waste.
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Re: Exercise improves health by evoking 'recycling'

Postby dime » Wed 20 Mar 2013 18:27

I think the effects of caloric restriction on autophagy are mainly due to protein restriction, not calories. E.g. methionine restriction according to some studies.

The only way to accurately determine the min. amount of protein that you yourself need daily in my opinion, is to stick to the same foods and activity level, and slowly decrease the protein amounts every month until you come to an amount that's too little. I'm kind of doing this, same food and then same exercises at the gym every day, so I'm very aware of my muscle strength. If my lifts start decreasing then it's most likely due to too little protein. I eat 70g protein at 73kg bodyweight, and my strength slowly increases with just this much protein. 50-60g protein would be perfectly enough just for maintenance. Bodybuilders would laugh at you to hear these amounts, when they typically eat 200-300+ grams.
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Re: Exercise improves health by evoking 'recycling'

Postby panacea » Thu 21 Mar 2013 15:57

One thing you discover when you try to formulate a low protein diet the difficulty of finding suitable foods. When the national Academy of Science established its Recommended Daily Allowances for protein, it started with the amount of protein and its breakdown products lost by the average adult male body per day. Since nitrogen is found in proteins but not fats or carbohydrates, its measure serves as a close measure of protein. Obligatory urinary nitrogen losses at about 37 mg/kg/day, fecal nitrogen losses at 12 mg/kg/day, perspiration, hair, fingernails, and sloughed skin nitrogen losses at 3 mg/kg/day and other losses at 2 mg/kg/day imply a protein loss of 0.34g/kg/day or 0.15g/lb/day. Any net recovery from the diet beyond that in the absence of growth is converted to carbohydrate (sugar) and burned for energy or then converted to fat. Of course energy is as legitimate a need as any other and there is nothing bad about getting it from protein, unless you have a condition like some kidney diseases for which a low protein diet is indicated.

Source:
http://proteincyclingdiet.wordpress.com ... wklbxs-11/
So, .34*73kg is 24.82g of protein per day minimum, much less than 70g/day. The author also notes that too little protein is more dangerous than too much, so most sources buff up the recommended intake for safety, but there is clearly a lot of room for potential improvement here, if we can determine how to be safe about it. Although the author is very adamant about eating some days and starving the others, as it induces authophagy which he claims requires the body to be lacking protein, I still don't see why it's necessary to go to the extremes of one day eating protein, one day not, or fasting for multiple days from it or even weeks, and then bulking up etc. It would make more sense to me to just eat a baseline, you will never have it totally correct anyway - some days you'll eat too little of it, some days more than you need, so that it averages out, and tiny amounts of autophagy happen each day, rather than really stressing your organs with excess eating to re-cooperate from frequent fasting.
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Re: Exercise improves health by evoking 'recycling'

Postby dime » Thu 21 Mar 2013 18:08

It would make more sense to me to just eat a baseline, you will never have it totally correct anyway - some days you'll eat too little of it, some days more than you need, so that it averages out, and tiny amounts of autophagy happen each day, rather than really stressing your organs with excess eating to re-cooperate from frequent fasting.
I absolutely agree.

Regarding that minimum amount of protein, you should calculate in it that I for example want to build some muscle too, so some extra is needed for that. Furthermore you can't translate the figure 1 to 1 to the protein content of foods, because
1) the body needs various amino acids, some more some less, and this may not overlap perfectly with the amino acid make up of the dietary proteins you ingest. We have some topic here on "protein quality" with respect to the amino acids as calculated by the FDA. Egg yolks and liver have about the highest quality of 80% or so, meat and fish are around here too at around 75%.
2) assimilation of protein may not be complete, e.g. in egg yolks some 10-15% of the protein is phosvitin which is very much undigestible.
3) especially when it comes to raw food I've seen studies that demonstrate raw protein is not so well digested, compared to cooked (e.g. fish). But they are all short term studies (at most months), so I'm assuming it takes some time to adapt to digesting raw foods. Experimenting cold turkey from cooked SAD will of course give such results.

You can do all the calculations and theory, but to transfer that to practice is extremely hard if not impossible. The calculations are enough to just have some general idea that you don't need huge amounts of protein to live. But if you want to fine-tune it to your case you have to experiment yourself. I stick to 70g for now, few months later I'll try 60 for example and see how that works. You have to start somewhere and as you said, a bit more is much safer than too little.

PS. I'd suggest you to break down your thoughts in smaller sentences. I know it's easier to just write down along as you're thinking, but it makes it much harder to read and understand.
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Re: Exercise improves health by evoking 'recycling'

Postby RRM » Fri 22 Mar 2013 08:02

dime wrote:I think the effects of caloric restriction on autophagy are mainly due to protein restriction, not calories.
Its both.
Insulin is triggered by both protein and sugars, and is a very potent autophagy inhibitor.
Autophagy is a survival mechanism, and therefore its also logical that it responds to both calorie- and protein-restriction.
Its a cellular adaptation to consuming too little calories / protein.
With autophagy switched on, the body can survive on less energy and protein.
Much of the organelles and redundant materials in cells can be used either for protein synthesis or energy.
dime wrote:especially when it comes to raw food I've seen studies that demonstrate raw protein is not so well digested, compared to cooked (e.g. fish)
Thats including all nitrogen sources,
so also damaged amino acids and newly created mutagens are included in that assimilated protein.
Net profits (for reconstruction purposes) will therefore be lower.
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Re: Exercise improves health by evoking 'recycling'

Postby panacea » Tue 26 Mar 2013 10:22

RRM, when you say insulin inhibits autophagy is this because insulin increases represent energy from diet?
In other words.. if the body senses food intake (through insulin) shut down cellular cannibalism as it's not necessary anymore.

This is what my logical guess would be, and if so, then I don't think low insulin levels would inhibit autophagy completely if you were eating even slightly less than the minimum amount needed to maintain current weight. There would still be a net loss in energy that the cells need to extract from autophagy, even if the effect isn't as dramatic as would be during fasting.

The essence of a theory being that the body is better at doing specialized tasks, such as repair or recycling, under special conditions where the body is: sleeping, digestive system free of or almost free of anything but water, etc, is that our bodies are designed to go through phases of nutrition, and then fasting, much like our waking and sleeping patterns - grow and resupply during the phase of nutrition or excess, and repair and recycle during moderation/fasting or sleep.
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Re: Exercise improves health by evoking 'recycling'

Postby RRM » Tue 26 Mar 2013 10:58

panacea wrote:RRM, when you say insulin inhibits autophagy is this because insulin increases represent energy from diet?
As a hormone, insulin directly 'instructs' cells. When insulin is elevated, autophagy is inhibited, by the direct influence of insulin.
Thats because the body wants to make use of all available dietary macro nutrients (as in nature, excess never lasts),
which happens more profoundly if the cells do not supply their own energy.
I don't think low insulin levels would inhibit autophagy completely if you were eating even slightly less than the minimum amount needed to maintain current weight. There would still be a net loss in energy that the cells need to extract from autophagy, even if the effect isn't as dramatic as would be during fasting.
Indeed.
Either our bodies are designed to go through phases of nutrition, and then fasting, much like our waking and sleeping patterns - grow and resupply during the phase of nutrition or excess, and repair and recycle during moderation/fasting or sleep. The essence of that theory being that the body is better at doing specialized tasks, such as repair or recycling, under special conditions
Yes, energy is more efficiently utilized during relative starvation and activity, and (re)construction happens more efficiently after a great influx of nutrients (and during rest).
There will be an optimum of balances somewhere. (preventing too much muscle break down for energy, for example)

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