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Dean Pomerleau

Cold Exposure & Other Mild Stressors for Increased Health & Longevity

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You could also stay at the ice hotel in Quebec, Canada. It's rebuilt every year and is open for a few months.

 

http://www.hoteldeglace-canada.com

 

Incredible artistic and structural endeavour, I'm thinking about the unique construction skills it involves, beyond the breathtaking decor. Do people really sleep in there?

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Haven't read it, but the article below looks interesting.

 

--Dean

 

Biochimie. 2017 Jan 2. pii: S0300-9084(16)30392-3. doi: 10.1016/j.biochi.2016.12.014. [Epub ahead of print]
 
A nutritional perspective on UCP1-dependent thermogenesis.
 
Bonet ML1, Mercader J2, Palou A3.
Author information:
 
Abstract
 
Uncoupling protein 1 (UCP1) is the hallmark protein responsible for cold- and diet-induced thermogenesis in brown adipose tissue (BAT). UCP1 activity is protective against body fat accumulation. UCP1 has re-gained researchers' attention in the context of obesity following the realization that BAT is present and can be activated in adult humans and of inducible UCP1-expressing cells in white fat depots. UCP1-mediated thermogenesis is activated by specific food compounds, which function by stimulating sympathetic nervous system activity to adipose tissues and/or by acting on the adipose cells directly or indirectly, through humoral factors released upon their intake. The impact, functional consequences and potential mechanism of action of macronutrients, micronutrients and bioactive compounds impinging on UCP1 expression/activity is discussed, as well as emerging links between human genetic variation and differential responses to potential thermogenic food ingredients. Advances in this field can help dietary recommendations and strategies for long-term weight loss/maintenance and improved metabolic health.
 
Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.
 
PMID: 28057582 [PubMed - as supplied by publisher]

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Holy cow. I've only read the abstract, but this study [1] found 13% lower mortality risk in people who regularly consume thermogenesis-inducing, BAT-boosting hot peppers.

 

--Dean

 

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

[1]  PLoS One. 2017 Jan 9;12(1):e0169876. doi: 10.1371/journal.pone.0169876.

 

The Association of Hot Red Chili Pepper Consumption and Mortality: A Large Population-Based Cohort Study.
Chopan M, Littenberg B.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0169876
http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0169876&type=printable

Abstract
The evidence base for the health effects of spice consumption is insufficient, with only one large population-based study and no reports from Europe or North America. Our objective was to analyze the association between consumption of hot red chili peppers and mortality, using a population-based prospective cohort from the National Health and Nutritional Examination Survey (NHANES) III, a representative sample of US noninstitutionalized adults, in which participants were surveyed from 1988 to 1994. The frequency of hot red chili pepper consumption was measured in 16,179 participants at least 18 years of age. Total and cause-specific mortality were the main outcome measures. During 273,877 person-years of follow-up (median 18.9 years), a total of 4,946 deaths were observed. Total mortality for participants who consumed hot red chili peppers was 21.6% compared to 33.6% for those who did not (absolute risk reduction of 12%; relative risk of 0.64). Adjusted for demographic, lifestyle, and clinical characteristics, the hazard ratio was 0.87 (P = 0.01; 95% Confidence Interval 0.77, 0.97). Consumption of hot red chili peppers was associated with a 13% reduction in the instantaneous hazard of death. Similar, but statistically nonsignificant trends were seen for deaths from vascular disease, but not from other causes. In this large population-based prospective study, the consumption of hot red chili pepper was associated with reduced mortality. Hot red chili peppers may be a beneficial component of the diet.

 

PMID: 28068423

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Nice ~adds possible credence to the three "Nature's Way-Cayenne, 450mg" capsules I've been popping a day.

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Nice ~adds possible credence to the three "Nature's Way-Cayenne, 450mg" capsules I've been popping a day.

 

The epidemiology much more strongly supports fresh chilis than supplements. In this study, they carefully excluded "ground red chili peppers," so the reported effect can really only come from fresh (tho' some do use whole, dried chilis).  In the earlier Chinese study on whose basis this study was in part modeled, the investigators initially asked whether people ate any hot spicy foods, and for those that did, they further asked “When you eat spicy foods, what are the main sources of spices usually used?”, with entries for fresh chilli pepper, dried chilli pepper, chilli sauce, chilli oil, and other/don’t know. Both fresh and dried chili peppers yielded significant inverse associations with total mortality, but only fresh chili pepper yielded significant negative associations with multiple specific causes of death (tho' in the new study death from vascular disease seemed to be the key factor). They did speculate however that an effect of other forms of chili might have been masked by the fact that "production of chilli sauce and oil usually requires more oil, and intake of pungent foods may be accompanied by an increased intake of carbohydrate-rich foods such as rice to relieve the burning sensation."

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I've been consuming about 1/4 hot chili pepper (thinnly sliced) a week, too.  ~Any more than that is greater than this pie hole is gonna allow!  :()

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Holy cow. I've only read the abstract, but this study [1] found 13% lower mortality risk in people who regularly consume thermogenesis-inducing, BAT-boosting hot peppers.

 

Nice!  Now if only there was a thermogenesis-inducing, BAT-boosting pepper that wasn't hot (so you could eat massive amounts without stomach cancer or vomiting, just the health benefits)!    ;)xyz

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So I decided to do more reading on olives and olive oil after learning of the BAT connection and other reported health benefits of high phenol EVOO.  Looking back at that study mentioned recently in this thread, it is specifically Oleuropein that was found to enhance UCP1 expression in BAT.  These guys discovered that specifically the Mission variety of olive (North America's only native olive variety?) from California presented in all analyzed samples significantly higher (5 times more) concentration of oleuropein aglycon than all Mediterranean varieties. Characteristically the Berkeley Olive Grove Mission showed the highest concentration among all studied samples at 397 mg/kg (but it turns out this wasn't even their best year, more to come). All Mission based olive oil tested, even within a blend, were found to be very rich in Oleuropein. This specific phenolic compound is associated with neuroprotection:

Olive-Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer’s Disease: In Vitro and in Vivo Studies

 

Anyway, something interesting happened with Berkeley Olive Grove last year, one of their products lab tested out with THE highest Oleuropein Aglycone ever recorded (compared with thousands of samples spanning many years).

 

On a whim, I decided to call Berkeley Olive Grove, mostly just to find out when the 2017 oil would start flowing. I ended up getting MUCH more than I expected!  The owner and farmer/orchardist himself, Darro Grieco answered my call, and I am so glad we connected.  He is the ultimate olive enthusiast/geek, we talked for a long time.  The latest crop has already been harvested and sent to the mill, but the oil is not yet returned (nor has lab testing been completed yet).  They won't be selling the new crop until sometime next month. This is his "down time" considering almost all of last years product is already sold out.  

 

Anyway Darro attributes his unusually high phenol content to his cultivation practices, he does "dry farming" (no irrigation despite an arid climate), completely organic (certified), and he stressed this part - very low density planting (he specifically said 65 trees per acre, versus other farms that do several hundred trees per acre).  He talked a lot about the lab testing, and then forwarded me all sorts of documentation.  I asked him about just eating olives vs. olive oil - like others here have mentioned, he didn't see them as equivalent - and he talked about how olives are completely inedible unless cured, and then he described some of the different curing methods, some are better than others, and how the phenols can be depleted by that process, but when I asked he admitted that he knew of no studies that demonstrated this definitively with lab testing (so for me I'm not completely convinced yet but its not looking all that good for whole olives from my point of view).

 

Finally, Darro mentioned on the call that he still has a little bit of this world record breaking organic mission classic olive oil left from last year's batch. Considering the stats on this liquid gold, it's also quite inexpensive, especially if you buy a gallon (transfer it to glass containers yourself). Looks like all the other lower phenol oils they produce are sold out, the really pungent stuff that people like us want is the last to sell out (go figure).  Anyway, the phenol content varies year to year, and I'm guessing this years product is not likely to break last year's record.  Of course I asked about the decline in phenols over time.  He told me that one of the labs kept a sample from him for one full year, not stored in any special way, just in clear glass, and exposed to normal room lighting, when they tested his oil a year later, the phenol levels were unchanged.  He believes this is the result of the very low free oleic fatty acids in his oil.  He even forwarded me documentation of this (the year old oil testing was done by Dr. Prokopios Magiatis, Univ. of Athens Department of Pharmacognosy and Natural Products chemistry).

 

8 Dec 2015: “Berkeley Olive Grove 1913 robust olive oils are among the top 2.5% or higher of the top
 
samples regarding the total phenolics compared with our database of more than 2,500 samples.”
 
It is exciting that we discovered in your samples very high concentration of a compound with
 
antihypertensive* activity named elenolide**. We are very excited about this discovery, a new field of
 
research have opened for us and for your product is something very important!!!
 
--Dr. Eleni melliou, World Olive Labs
 
17 Nov 2015, from Scientific Evaluation Report for the Olive Oil “Berkeley Olive Grove”: It should be
 
noted that oleocanthal, oleacein and oleuropein aglycone present important biological activity and they
 
have been related with anti-inflammatory, antioxidant, cardioprotective and neuroprotective activity. The
 
levels of oleuropein aglycone are the highest that have been recorded in the international database which
 
has been developed by the University of Athens. --Dr.Eleni Melliou
 
Nov 17, 2015: The name Oleomissional (in the honor of Mission variety from California) has been accepted
 
by the international olive oil council and is going to be published in the November issue of the official
 
journal of the council. It is formally mentioned that the new ingredient was isolated for the first time from
 
the olive oil of Berkeley Olive Grove.
 
Two weeks ago, in Spain we announced the results of the clinical study that was performed in Davis with
 
olive oil rich in oleocanthal and oleacein. For the first time we were able to show that an olive oil with
 
oleocanthal+oleacein around 450 mg/Kg (similar to your last year's Classic) can have a similar effect on
 
humans like ibuprofen in the prevention of thrombosis and protection from heart attack and stroke.
 
–Dr. Prokopios Magiatis, Univ. of Athens Department of Pharmacognosy andNatural Products chemistry
 
Dec 10, 2015
 
We checked again yesterday the sample "Classic" that you had sent us in January and it is still great. After
 
almost one year the levels of phenols are the same. So it is a very stable oil in contrast to some other oils
 
that we have measured and can lose a significant part of their phenolic content. It is a great advantage of
 
your oil.  The sample was kept at room temperature in a clear glass vial under conditions similar to a supermarket
 
shelf. –Prokopios Magiatis
 
    
 
Berkeley Olive Grove EVOO Packs a Punch       Recent research shows one California extra virgin olive oil just might be among the world’s healthiest.      
 
 
 
 
*  I send you attached the certificates for the 3 samples. The results are
excellent!!! Congratulations for an other year you have high quality!!!
    In next days we are going to send you the advanced certificate (briefly
your samples are among 2.5% or higher of the top samples regarding the
total phenolics compared with our database with more 2.500 worldwide
samples!)
    It is exciting that we discovered in your samples very high concentration
of a compound with antihypertensive activity named elenolide.
we are very excited about this discovery, a new field of research have
opened for us and for your product is something very important!!!
 
 
 
Edited by Gordo

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Thanks, Gordo, that is a very valuable and fascinating account. Excellent find, and a great report!

 

That said, a few observations, if I may. The claim "He believes this is the result of the very low free oleic fatty acids in his oil." - however oleic fatty acids are an integral part of what we look for in health benefits of EVOO. The super-high levels of oleuropein have to be seen in context - is this at the cost of other elements in the EVOO (as implied by the above claim) - perhaps that is not optimal. After all, if we are interested in super high levels of oleuropein, then you can look to olive leaf extracts and powders with off-the-charts levels (much higher than here) - see other threads where we discuss oleuropein and olive leaf powder/extracts. 

 

More importantly, there is the old black box methodology that I always look for. I am extremely reluctant to guide my dietary (or generally: health) practices based on biomechanical speculation about how some compound or another has benefits/harms. Sometimes it's unavoidable, simply because we have no other data to guide us. But we've all seen such speculation turn out to be completely wrong so often that we should all be chastened by now: for example how many vitamins have we seen work splendidly in one context (whole foods), while counterproductively when supradosed or isolated in pills? One approach is to regard the human body as a black box: you input on one end, and get results on the other, but you don't speculate on what happens inside the box. I leave speculation about how the insides of the box work, to scientists. I am not a scientist, so I just look at studies - if the study determines that EVOO is beneficial to health - you put it into one end of the black box (consume it) and at the other end the result is: more health, then that's good enough for me. I don't try to then isolate some specific mechanism or compound, as it's liable to be completely wrong when science learns more. So if you based on purely speculative reasoning on what is happening inside the box, now tell me that a new kind of EVOO - let's call it SUPEREVOO must be better, my response is: where is the study showing it passes the black box test - show me SUPEREVOO going in, and MORE health coming out the other end, and I'll be all over the SUPEREVOO. But for now, why not stick to WHAT WE KNOW FOR SURE - EVOO that has passed the black box test and health benefits are obtained. We DON'T know what happens when SUPEREVOO is put into one end of the black box - so speculating about what comes out the other (more health) is just that: speculation. Why not stick to what we know?

 

Of course, inevitably we do have to gamble on some speculation and I suppose in this case at least we are indeed dealing with EVOO that has a long record of health outcomes - unlike f.ex. olive leaf extract. So it's worth taking a flyer on this EVOO - and thank you for this fantastic and fascinating find, Gordo. That said, while I might grab some, I don't think I'll limit myself to just this EVOO for life - I'll continue to consume the EVOO that has a lengthy track record - Meditarranean olive varietals. The Mission varietal has no such track record, so it has not passed the black box test for me, thus it is something of an occasional treat for me. YMMV.

 

Btw. some  of the other claims are odd too - ibuprofen is generally as most NSAIDS (with the exception of aspirin) associated with greater risk of heart attack, not "protection from hear attack".

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All:

 

Thanks, Gordo, that is a very valuable and fascinating account. Excellent find, and a great report!

 

That said, a few observations, if I may. The claim "He believes this is the result of the very low free oleic fatty acids in his oil." - however oleic fatty acids are an integral part of what we look for in health benefits of EVOO.

 

We should maybe move these posts into a separate EVOO thread, yes?

 

A quickie: to be clear, "free oleic acid" does not mean "percent total fatty acids as oleic acid:" is a synonym for "free fatty acids" (FFA), ie, fatty acids hydrolyzed out of their triglyceride structure. It's thus unrelated to the overall %oleic acid in the oil: FFA is assayed as free oleic because it's the dominant fatty acid even in low-oleic oils and can thus be conveniently measured as a reading of overall TG hydrolysis. FFA is  a quality marker, as it generally indicates poor fruit quality, a long delay between plucking/falling off the tree and crushing, or infestation with mold or insects.

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Yea, probably move to another thread, although my original posts on EVOO in this thread were in the context of their connection to BAT which is relevant to this thread.

 

Regarding that "ibuprofen" comment, it was an email from a researcher, I think he really meant "aspirin", but not sure, I briefly searched google scholar for the clinical study he mentioned but nothing immediately caught my attention, not sure it has been published yet.

 

Regarding Oleic Free Acidity - the lower the better the health benefits:

PolyphenolComparisons_787x612.png

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I just browsed Wim hof's site, there are interesting practical suggestions on how to start practising cold exposure (breathing exercise + cold shower).

He also offers a free minicourse plus other courses to develop gradually resistance to cold.

Edited by mccoy

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mccoy,

 

By the way, guys, you sure must know about the absolute master of cold exposure, the iceman, Wim Hof himself. A reference to him cannot be avoided in such a thread. Rich Roll has a very good interview with him.

 

Of course. Typing "iceman" in the search box at the top of this page will return the 7 posts where we've talked about Wim in this thread alone, not including your own.

 

--Dean

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Thanks Dean, I read your comments on the Rich Roll podcast. It seems that Wim hof is an intuitive master of the technique. I liked the interview even though it lacks detailed scientific explanations. He's not a medical man, he's what we might define a technical operator and has refined the method to withstand cold temperatures to an extreme level. 

 

I wonder if anyone has followed his course here. I just read his instructions on cold shower, which I've been practicing for decades and they are sensible, especially in the part of very gradual exposure. I used to practice cold exposure (in the winter) for about 10 years and I must say the body gets accustomed naturally to it, until a certain extent. For example, I could not swim easily into the wintry sea. After some threshold probably specific techniques are required. It also seems that Pranayama (breath-control techniques) is a vital part of Wim Hof's method, especially the g-tummo method or some variation of it, an old renowned Tibetian practice cited in the articles.

 

Another important issue is this: barring acute events of hypothermia and frozen flesh, is there an exposure threshold beyond which the longevity benefits of cold exposure turn into detrimental effects, and where is such threshold. 

 

One detail I remember from the podcast: the iceman eats one meal only at 6 PM, so it is reasonably to believe that he practices cold exposure on an empty stomach. That's a very important detail to remember, especially if immersion in cold water is concerned.

 

I'm going to read more about his method and the previous posts in this thread. 

Edited by mccoy

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All,

 

New paper reinforces previous observations that quercetin (e.g. from onions, esp. the peal) promotes WAT → BAT conversion [1].

 

--Dean

 

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

J Nutr Biochem. 2017 Jan 12;42:62-71. doi: 10.1016/j.jnutbio.2016.12.018. [Epub ahead of print]

 
Quercetin, a functional compound of onion peel, remodels white adipocytes to brown-like adipocytes.
 
Lee SG1, Parks JS2, Kang HW3.
Author information:
 
1Food and Nutritional Sciences, Department of Family and Consumer Sciences, North Carolina Agricultural and Technical State University, Greensboro, NC, 27411.
2Department of Internal Medicine-Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157.
3Food and Nutritional Sciences, Department of Family and Consumer Sciences, North Carolina Agricultural and Technical State University, Greensboro, NC, 27411. Electronic address: hkang@ncat.edu.
Abstract
 
Adipocyte browning is a promising strategy for obesity prevention. Using onion-peel-derived extracts and their bioactive compounds, we demonstrate that onion peel, a by-product of onion, can change the characteristics of white adipocytes to those of brown-like adipocytes in the white adipose tissue of mice and 3T3-L1 cells. The expression of the following brown adipose tissue-specific genes was increased in the retroperitoneal and subcutaneous adipose tissues of 0.5% onion-peel-extract-fed mice: PR domain-containing 16, peroxisome proliferator-activated receptor gamma coactivator 1α, uncoupling protein 1, fibroblast growth factor 21 and cell death-inducing DFFA-like effector. In 3T3-L1 adipocytes, onion peel extract induced the expression of brown adipose tissue-specific genes and increased the expression of carnitine palmitoyltransferase 1α. This effect was supported by decreased lipid levels and multiple small-sized lipid droplets. The ethyl acetate fraction of the onion peel extract that contained the highest proportion of hydrophobic molecules showed the same browning effect in 3T3-L1 adipocytes. A high-performance liquid chromatography analysis further identified quercetin as a functional compound in the browning effect of onion peel. The quercetin-associated browning effect was mediated in part by the activation of AMP-activated protein kinase. In summary, our study provides the first demonstration of the browning effects of onion peel and quercetin using both animal and cell models. This result indicates that onion peel has the potential to remodel the characteristics of white adipocytes to those of brown-like adipocytes.
 
Copyright © 2017 Elsevier Inc. All rights reserved.
 
PMID: 28131896 [PubMed - as supplied by publisher]

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I want one:

 

A Real Life “Hibernation Chamber” is Being Made For Deep Space Travel

 

https://futurism.com/?p=70021

 

 

Therapeutic Hypothermia

 

Manned, long-term, deep space missions are an exciting prospect, but one that remains in the realm of distant possibilities–particularly because we don’t have all the technological innovations needed to make it happen.

 

One major consideration is the time it takes to reach the destination. Mars, which is at the top of various space programs’ go-to destinations for manned missions, is about six months if travel time away from Earth. If we wanted to explore even further, keep in mind that New Horizons, the fastest spacecraft to leave Earth, took nine and a half years to reach Pluto.

 

Science fiction conveniently sidesteps this challenge by putting the space explorers into deep sleep–a state of suspended animation. But slowing the human metabolism down while ensuring that a person will stay alive for extended periods is a lot easier said than done."

 

Spaceworks

 

Spaceworks however, led by John A. Bradford, is proposing to use a method they refer to as “therapeutic hypothermia.” The process involves cooling the body a little below the normal body temperature (37 C), to slow down heart rate and blood pressure. This process is already being used in the medical world. By bringing the body temperature of patients undergoing treatment for cardiac arrest or traumatic brain injuries down to 32 and 34 degrees Celsius, doctors have more time to address the issues.

 

The method normally allows patients to stay in stasis for about 2-4 days, but has worked for as long as two weeks. Spaceworks not only believes they can extend this for months, but also that they can create the technology needed to automate the process and apply it for deep-space missions.

 

Suspended Animation

 

Unlike the cryo-chambers depicted in films however, where row upon row of space travelers are left in suspended animation in individual pods, Spaceworks is conceptualizing an open chamber that allows the crew to go into stasis in shifts.

 

“There would be some robotic arms and monitoring systems taking care of [the passengers]. They’d have small transnasal tubes for the cooling and some warming systems as well, to bring them back from stasis,” Bradford describes an interview with Quartz.

 

This not only addresses concerns of adding too much weight to a spacecraft, but also ensures that there will be people awake to manage possible emergencies and conduct standard monitoring.

 

As for the long-term health effects of space travel, Spaceworks is trying to find ways of incorporating exercise into stasis. The team is looking into using electrical stimulation, which is already used to aid physical therapy. Having this technology in place also solves a lot of logistical issues for manned space missions. With crew members awake, you have to factor in the volume of food, water, and air needed to keep them alive for months and years at a time. It could also help manage the psychological impact of long-term space travel and hopefully lower the risk of space crews succumbing to depression, claustrophobia, or anxiety.

 

According to Spaceworks, they are due to begin animal testing next year, with human testing set to follow after in space and on the International Space Station."

 

Don't you want one, too?

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I'm back practising cold exposure. Although I still could not read all this thread from the beginning (but it is one of my short-medium term goals) I'm not new to it, having practised that in my youth.

I don't know physically, but sure mentally this has a definite rejuvenating effect, hurling me decades back in time.

I started lengthening the duration of my usual morning cold shower until a paralyzing numbness manifests. And I do that twice a day.

Plus, I'm going around with no coats nor sweaters. Sometimes just with a T-shirt, but that definitely is noticed, and people starts asking me.

 

I'd be curious to hear your answers to people asking how come you are not cold.

 

I have a few answers ready, depending on who asks.

 

From serious ones, like 'My new heating plant is really working too well, I didn't expect it'  to more facetious ones like 'This must be the onset of menopause to me'. All in all, I'm having some fun out of it.

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When someone makes a comment I usually say something like "coats are for wimps" or "cold is good".

If you don't have time to read this thread, I did summarize the science in a very condensed alternative form over at LongeCity (it's also the first link in my profile if you click my picture).

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Good summary Gordo, also I'm impressed by the low GI without hypoglicaemia (actually I already noticed that in another thread here but forgot to ask). Did you post your fasting GI before starting the practice of CE? If you did, I missed that.

 

Cold showers: if the water is really cold, I can definitely feel the blood pressure spike, at night more than in the morning (that's what I noticed and don't know the reason). If there are potential problems then maybe it's better to increase a little the water temperature and stay longer, possibly showering the head as well. Or maybe it's better to start with a 'cold air shower'.

 

I also subscribe to the quote below:

 

there is nothing quite like the feeling you get after stepping out from a cold shower - I have come to really enjoy this now, the sense of invigoration and positive alertness is a wonderful way to start your day! 

 

 

Also, do you shower your head or keep it out of the water? the former is obviously more severe and more similar to an immersion.

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Because of my evident fixation with mTOR, I went and searched for the possible interactions with CE and mTOR. The top google link forwards to this thread (or maybe another which links to this graph):

 

 

 

 

WQK0Qhs.png

 

 

 

In the above diagram there seems to be some some contrasting effects on mTOR from cold exposure.

Activation of adiponectin and subsequently of AMPkinase tends to inhibit mTOR. Cold, according to the diagram, will increase blood adiponectin. Interestingly, it seems that CR increases adiponectin as well (but there is no activating arrow from CR to adiponectin in the diagram).

Activation of the cAMP-PKA pathway (presumably caused by increased  epinephrine=adrenaline stimulated by cold) tends to activate mTOR.

 

So according to the diagram we are having a tug-of-war effect between AMPK and PKA. 

 

Also, the diagram does not illustrate the effects of CR on glucose and amminoacids, both of which would imply an inhibition on mTORC1.

 

Right now I have no time to delve further in the subject, but so far I found no other articles on the stimulation of mTOR by PKA other than in adrenocortical cells.

 

Also, AFAIK longevity is boosted in general by mTOR downregulation, although I agree with Dean that a degree of cell growth and proliferation is necessary and often advantageous. We get back to the balance between repair & manteinance (↓mTOR) and growth and proliferation (↑mTOR).

 

That's a complex issue, though, since it often depends on the specific tissues and which I'm only starting to understand very little in a few of its aspects.

Edited by mccoy

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Found this Nature article from Sebastien et al. 2016

 

mTORC1 is Required for Brown Adipose Tissue Recruitment and Metabolic Adaptation to Cold

which illustrates how cold upregulates both mTORC1 and mTORC2 in BAT, by two proposed routes:

 

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

 

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

 

It is very interesting to notice that the 2nd metabolic route has strict similarities with the activation of mTORC1 in myocites, or muscle cells:

 

2b) MECHANICAL LOAD→mechanoreceptors→Akt→mTORC1

 

Also, both the above #2 routes bypass the Insulin-IGF1→Akt→mTORC1 pathway, that is, BAT synthesis and MPS do not need insulin-IGF, since cold, or load, govern the activation of mTOR.

 

The cited article illustrates the COLD→Norepinephrine receptors*→Akt→mTORC1 route.

* I construe NE by NorEpinephrine, which is also a neurotransmitter and is released by cold 

post-7347-0-26958400-1486852265_thumb.jpg

Edited by mccoy

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After the above, it stands clear that the dualism between mTOR upregulation and downregulation depends often on the target tissues.

 

For example, since it seems that muscle cells hypertrophy and BAT hypertrophy are good for longevity, then mTOR activation in these tissues is good. Of course, the local activation should not imply a general amplified mTOR activity, otherwise cancer cells might develop in organs. Probably the issue is one of balancing maximum growth in specific tissues and barely necessary growth in other tissues, becoming an optimization problem.

 

One example: COLD upregulates mTOR in BAT and it doesn't need increased food intake which would upregulate mTOR in other tissues like hepatocites, prostate cells, and other organ cells. Situation seems straightforward.

 

On the other hand, increased hunger by increased energy use (thermogenesis) might theoretically result in an abundance of nutrients which would chronically amplifiy mTOR's activity in the organs (unwanted effect). This would also be balanced by the anti-insulinic effect of BAT and who knows how many secondary homeostatic mechanisms...

Edited by mccoy

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Previous pre-CE fasting glucose low was 64, but normally was in the 70's.  When I do cold showers I hit the entire body including the head, I like to do stretching exercises during the cold shower.  The blood pressure rise is the result of rapidly constricting blood vessels, as long as you don't have heart disease, I would expect this to be beneficial to your cardiovascular system.  Wim talks about these things in a new video just posted last week:

 

https://youtu.be/mxCGDFlH1_k

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