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Cold Exposure & Other Mild Stressors for Increased Health & Longevity

Cold Exposure Exercise Fasting UCPs UCP1 UCP3 FGF21

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#21 KHashmi317

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Posted 22 January 2016 - 02:11 AM

Unfortunately the CR email list archives appear to be down for the count.  :(xyz

I was just going to post on that.

There's some content I posted on the List that I thought could benefit from re-posting (on this forum).

Not sure how long the archs have been down or whether there are plans for re-up. It's important to have them back up ... 'cause even on lifelong CR, my memory banks are springing some leaks ;)


Edited by KHashmi317, 22 January 2016 - 02:12 AM.


#22 Dean Pomerleau

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Posted 22 January 2016 - 03:14 AM

Khurram,
 
Great profile picture - it's nice to see your face again after so many years!
 
Regarding the email list archives. I couldn't agree more. They are a treasure trove of wisdom and information. It will be tragedy if they are forever unavailable. I have several hundred megabytes of the archives thanks to James Caine, but only starting in 2008 and only in raw & unparsed format - very hard to search. But everything before that, when I, Sherm, you, Saul, Warren and others were most active on the list is entirely unavailable right now, at least as far as I can tell.  :(xyz 
 
Brian has mentioned several times they are working on making them available again, but it's been this way for quite a while now - many months at least.
 
--Dean

There will never be peace in the world while there are animals in our bellies.

#23 KHashmi317

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Posted 23 January 2016 - 12:14 AM

 

Khurram,
 
Great profile picture - it's nice to see your face again after so many years!
 
Regarding the email list archives. I couldn't agree more. They are a treasure trove of wisdom and information. It will be tragedy if they are forever unavailable. I have several hundred megabytes of the archives thanks to James Caine, but only starting in 2008 and only in raw & unparsed format - very hard to search. But everything before that, when I, Sherm, you, Saul, Warren and others were most active on the list is entirely unavailable right now, at least as far as I can tell.  :(xyz 
 

 

That photo is from 2002. It's the only pose I could find to show all of me compressed in one small frame!

 

About the archs ... I don't get it??? I know that less than a year ago, I could access them FULLY (I think -- at least my legacy mails were in there). IAC, I hope we get them back. There's gold in them thar hills.

 

About cold exposure -- again, the archs would help as the topic was brought up several times -- but you bought up the Walford paper on hibernation and torpor.

And perhaps as importantly, that cold exposure doesn't produce benefits as a result of inducing a hibernation-like state of torpor and reduced metabolic rate, as previously thought (by Roy Walford and others, citation (35)) but quite the opposite. The benefit results from (or at least occur in the presence of) an increased metabolic rate exhibited by skinny CR mice housed in relatively cool conditions in order to maintain their body temperature: [...]

 

 

Recall however, at CRII, that Jamie Barger described "Calorie Restriction as a [potential] hibernation mimetic. "

 

 

Michael Rae noted that the LS curves of hibernating and CR animals were similar.

 

A few weeks ago the Cambridge Univ. weekly podcast of The Naked Scientists discussed The Hidden World of Hibernation.

 

 

Especially interesting is the segment starting: 39:04 - Dismantling brain cells:

 

 

Though the idea of a long sleep may sound pretty tempting, animals actually put themselves through an awful lot. They are continually cooling and reheating their bodies, putting huge stress on their organs, and some even make themselves diabetic. Hibernation is clearly no picnic, and things get even Neuronsworse as, in an attempt to save energy, animals will dismantle the synapses in their brains. These are the parts of the neuron that send and receive signals and without them we’re all pretty useless. But what’s even more amazing is that when it’s time to “wake up”  they’ll put them back together again, just as they were. Professor Giovanna Mallucci is a clinical neuroscientist at Cambridge University and she explains to Connie Orbach how this actually works.

 
Giovanna -  I think you’ve heard already from our other speakers, that there’s lots of processes that slow down and are shut down for hibernation including metabolism.  And one way to save energy is to stop the brain using its energy and the dismantling of synaptic connections between brain cells is a way of doing that.  What happens is, on cooling there is a retraction of what we call the “dendritic arbour”, you know all the connections and branches of a brain cell that’s connecting to another and the actual contacts - it’s like unplugging a plug from its socket, they are just removed so that no energy flows.  When they rewarm there’s a signal to reconnect these structures; how that exactly happens is absolutely not known and very, very interesting to us but we do know a lot about the processes that drive that regenerative capacity.
 
Connie - Is this happening all over the brain?
 
Giovanna - Yes, it’s happening all over the brain and all of us all the time.  So there’s a balance between pruning and generation or regeneration to maintain a sort of status quo and learning and memory need new synapses and then you prune and get rid of all your excess synapses when you sleep and other conditions.  But the capacity for regenerating synapses and refreshing them is part of repair and it’s called “structural synaptic plasticity.”
 
Connie - So let me just get this right. So what’s happening with animals in hibernation is a much more extreme version of actually something that’s happening all the time in humans and animals?
 
Giovanna - Correct, that’s exactly right.
 
Connie - So how have you been using this then in your work?
 
Giovanna -   So we know that in neurodegenerative diseases like Alzheimer’s, which is the prototypical disease but also many of the others.  The earliest thing that happens, before you get the brain cell degeneration, is that synapses are lost and as synapses are lost memory goes down - what we call cognitive function goes down, and it’s just not clear why this is early loss of synapses which is such an important stage in these diseases, and it’s important a) because it give you symptoms and b) because it's reversible.  So that’s the stage before the brain cells have died, before the neurons have died when, actually, if you can increase synapse number you can restore memory so it’s a very attractive, targetable point of intervention.  And our starting hypothesis was that the reason that synapses are lost early in Alzheimer’s disease and early in Parkinson’s disease and other disorders is because there’s a failure of this regenerative capacity that is part of our normal structural plasticity.  We used hibernation or induced laboratory hibernation in mice to test the ability of synapses to regenerate themselves in mouse neurodegeneration models.
 
Connie - And what did you find out - what’s happening?
 
Giovanna - So first of all we found very interestingly that mice which don’t normally hibernate, can hibernate in all the ways that you would normally expect.  So if you cool them: they’ll drop their body temperature, they’ll dismantle their synapses and they’ll go into torpor and then, when you re-warm them, they come completely back to normal again.  And what we found out was that normal mice dismantle and reassemble their synapses but the mice that we used that had neurodegeneration models - that’s Alzheimer type mice, and mice with prion disease - that’s another neurodegenerative disease.  They failed to reassemble their synapses so they could unplug the plugs but they couldn’t put them back in again and this lack of degenerative capacity gives us a good idea of why there’s such an early loss in synapses.
 
Connie - Did you get a bit deeper into this?  Did you get to see the protein that’s involved - is that right?
 
Giovanna - Yes we did. So hibernating and cooling does two things to you: it shuts down metabolism and it shuts down protein synthesis, but there’s a group of proteins that are upregulated and these are called “cold-shock proteins,” and they’re a relatively new family of proteins.  And one of these which is called “RBM3”, which is RNA Binding Motif Protein 3, is highly expressed in the brain and by being upregulated during hibernation that protein keeps a number of really important critical Messenger RNAs, that you need for survival, ready to make into proteins when you wake up.  And we found out that RBM3 is failing in the Alzheimer’s brain, and if we put it back in, we can rescue them.
 
Connie - So you found this protein, RBM3 - where do you go now?
 
Giovanna - So, we didn’t find the protein; I mean the proteins a known cold shock protein.  What we’ve done is associate it with the failure of structural plasticity in neurodegenerative disease in Alzheimer type mouse models and what we now want to do is understand the relevance for human disease.  Because what we found in the mice is that if you put the protein back in it’s incredibly protective, it gives them new synapses, it stops them getting neurodegeneration, it stops them getting memory loss, and it protects them in the long term and you can do that by either cooling the mice early to boost their indodgenous or their own RBM3 levels, or by putting it in artificially.  So now, obviously, this is a way in for neuroprotection for human disease but cooling itself is not realistic or practical in the long term.  It is used medically; it’s used in newborn babies that have had hypoxic damage; it’s used in post-stroke and it’s used in cardiac surgery, and in many forms of neurosurgery.  So we thinks that that’s acting through RBM3 and our ideal would be to be able to manipulate RBM3 levels for protection without having to cool.


#24 Dean Pomerleau

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Posted 23 January 2016 - 05:29 AM

Thanks Khurram!

 

Regarding the archives - yes it wasn't too long ago that they were available. And as I understand it the information is definitely not lost. Perhaps Brian or Tim could give us an update and the plan (if any) to bring them back on-line.

 

Regarding cold exposure (CE).  I think I agree with you and the evidence you share regarding CE and it relationship to hibernation/turpor. H/T have both 'passive' and 'active' mechanisms and benefits.

 

As an example of passive benefits, lower (body) temperature reduces the rate of certain harmful chemical processes in the body - perhaps processes like protein crosslinking & glycation.

 

Active mechanisms (that actually require more fuel rather than less) might be the uncoupling of mitochondria energy production to generate heat rather than ATP, but in the process also making the mitochondrial energy production 'cleaner' (fewer free radicals generated) as a side benefit.

 

I see CE as sort of like CR and exercise, which are both 'master stressors', that put pressure on the organism to hunker down and clean up its act to survive the ordeal. The organism responds to such challenges in a multitude of beneficial and yet-to-be-fully-elucidated ways, which improve health & longevity, at least up to a point.

 

But beyond some point, the stress becomes too great to cope with and does permanent damage. So starving to the point at which the body catabolizes it's own vital organs, or running an  ultramarathon at a pace that damages heart tissue, or freezing to the point that one's heart stops beating, are all unlikely to be helpful   :)xyz.  The fact that hibernating animals don't live longer than "warm" animals doesn't surprise me. The conditions and impact on the body of true hibernation may be too extreme and prolonged a stressor to be beneficial, like starvation or ultramarathoning.

 

Thanks for sharing that interview. I'd never heard of "cold shock proteins" or RBM3. Fascinating! It looks like one more mechanism by with CE might be beneficial, in this case for cognitive function by preserving synapses and neural plasticity.

 

In fact the researcher seems to have an attitude that's very similar to CR researchers, when he says:

 

Because what we found in the mice is that if you put the protein back in it’s incredibly protective, it gives them new synapses, it stops them getting neurodegeneration, it stops them getting memory loss, and it protects them in the long term and you can do that by either cooling the mice early to boost their [edo]genous or their own RBM3 levels, or by putting it in artificially.  So now, obviously, this is a way in for neuroprotection for human disease but

cooling itself is not realistic or practical in the long term...

 

In other words, it's the same story we hear from CR researchers all the time - "CR has amazing benefits but we can't expect people to actually do it, so we're going to try to find a pill to mimic it.'

 

In the meantime, some of us are willing and able to actually do it. 

 

--Dean


There will never be peace in the world while there are animals in our bellies.

#25 Saul

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Posted 24 January 2016 - 05:16 PM

Hi Dean and Khurram!

 

I always was fascinated by the "rats with cold feet" study -- it's fascinating to see that the advantages of cold exposure could be due to the raising of the FGF21 protein -- which is also raised by IF (and, I'd guess, standard CR) and exercise.  My intuition:  All of these may extend mean, and maybe even maximal, lifespan (in the case of "exercise", it probably matters "what kind".  I'd guess that aerobic, but not strengthening, exercise is the "good" kind).

 

Khurram, I don't like being cold either -- but it's unavoidable in Rochester, NY -- and it's nice to see that, together with CR, it's probably good for you.

 

:)xyz

 

It will be fascinating to see further info on the role of the FGF21 protein.

 

In the meantime, I strongly agree with Dean -- it's not a good idea to supplement FGF21.

 

 -- Saul



#26 nicholson

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Posted 24 January 2016 - 10:15 PM

Hi Dean:

 

"Whenever I see someone use the word "surely"........... "

 

Just to be clear, when I use the term "surely" I mean it to be interpreted as meaning:  "It seems highly probable to me that ..... ".  There are seven keystrokes in "surely " and 36 in the alternative.  So "surely" does seem rather more efficient. 

 

The Oxford Dictionary's explanation of it: "Used to emphasize the speaker’s firm belief that what they are saying is true and often their surprise that there is any doubt of this" contains over 100 characters.

 

I had thought that that was the meaning others attached to the word also?  But perhaps not?

 

Rodney.



#27 Dean Pomerleau

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Posted 25 January 2016 - 03:46 AM

Rodney,

 

It was quite clear what you meant to convey by your use of the word 'surely'. And it is more efficient than writing out the alternatives, as you point out.

 

It's just that I've internalized the rule-of-thumb that one of my favorite living philosophers, Dan Dennett has described in his really good book Intuition Pumps and Other Tools for Thinking, namely that one way to spot a weak argument is to look out for the word 'surely'. Quoting Dennett:

 

When you’re reading or skimming argumentative essays, especially by philosophers, here is a quick trick that may save you much time and effort, especially in this age of simple searching by computer: look for “surely” in the document, and check each occurrence. Not always, not even most of the time, but often the word “surely” is as good as a blinking light locating a weak point in the argument. Why? Because it marks the very edge of what the author is actually sure about and hopes readers will also be sure about. (If the author were really sure all the readers would agree, it wouldn’t be worth mentioning.) Being at the edge, the author has had to make a judgment call about whether or not to attempt to demonstrate the point at issue, or provide evidence for it, and—because life is short—has decided in favor of bald assertion, with the presumably well-grounded anticipation of agreement. Just the sort of place to find an ill-examined “truism” that isn’t true!

 

It's very much like the signature you were using at the bottom of your posts up until quite recently about "conventional wisdom" often turning out not to be true when thought about critically.

 

--Dean


There will never be peace in the world while there are animals in our bellies.

#28 Dean Pomerleau

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Posted 27 January 2016 - 05:50 PM

All,

 

I've collected a ton of research in both rodents and humans documenting the link between cold exposure, reduced core body temperature and longevity.

 

Here is a good overview diagram of the multiple mechanisms involved. As I've said, cold exposure is like CR in that it has multiple beneficial effects on metabolism and the aging process.

 

nihms-50090-f0001.jpg

 

I'm not sure when I'll be able to pull it all together into a single (or even multiple) posts. But for anyone interested, I've created a web page with all my notes and references on the topic.

 

A few highlights:

  • Calorie restriction linearly reduces core body temperature. Such reduction may be integral to the longevity benefits of CR. Raising the housing temperature of rodents on CR (and hence core body temperature as well) erases the benefits of CR - as discussed earlier in this thread.
  • Cold exposure upregulates uncoupling proteins (UCPs) in muscles as well as both white and brown adipose tissue (WAT and BAT), reducing reactive oxygen species (ROS) production by mitochondria, decreasing oxidative damage and increasing telomere length.
  • Mutations in the UCP genes are associated with increased human longevity.
  • Cold exposure upregulates expression of FGF21 in both the liver and BAT. FGF21 results in higher insulin sensitivity (via less fat accumulation in muscles), reduced cholesterol, and prevents atherosclerosis in APOE-knockout mice. Thus cold exposure could be especially beneficial for people with the APOE4 allele that increases one's risk for cardiovascular disease and Alzheimer's disease. FGF21 has also been shown to extend lifespan in mice without reducing calories.

 

It's fascinating stuff and provides pretty convincing evidence of the health and longevity benefits of cold exposure.

 

--Dean


There will never be peace in the world while there are animals in our bellies.

#29 Dean Pomerleau

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Posted 27 January 2016 - 06:29 PM

BTW - for those of you unlucky enough to live in a warm climate, don't despair.  :)xyz

 

Right now it's cold enough in Pittsburgh to not be necessary, but once it warms up I'm planning to buy one of these two "cooling vests" in order to continue my experiment with cold exposure.

 

--Dean


There will never be peace in the world while there are animals in our bellies.

#30 Gordo

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Posted 31 January 2016 - 10:26 AM

I am fascinated by this.  I checked out your cooling vest links.  From the second one:

"Phase Change Material (PCM) releases long-lasting, temperature-specific 58F (14 degrees C), cooling relief.

*Phase Change Material (PCM) is 30% lighter than water."

 

Any guesses as to what the PCM is?  I'd like to make my own replacement inserts for continuous cooling experiments (the ones they sell are expensive, and just one vest isn't going to cut it).



#31 Dean Pomerleau

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Posted 31 January 2016 - 01:29 PM

Gordo,

 

Any guesses as to what the PCM is?

 

Wikipedia is your friend  :)xyz. The wiki page on phase-change materials has a plethora of information, both on natural PCMs, as well as commercially available PCMs pouches, along with links to their website. Obviously many (all - eventually) material change phase as temperature varies, although only a relatively few do so anywhere near human body temperature. Here is an interesting FAQ about commercial PCMs from one of the manufacturers. This 59degF PCM is made from "agricultural sources" (code name for animal and/or vegetable fats - probably not vegan, FWIW...).

 

 I'd like to make my own replacement inserts for continuous cooling experiments (the ones they sell are expensive, and just one vest isn't going to cut it).

 

I'm glad someone else is going to try experiments in deliberate cold exposure. Please me us know your experiences!

 

From the Wikipedia list, it looks like there are enough common materials that change phase in the neighborhood of 60F that you could make DIY inserts.

 
But you could also buy the packs ready-made. Here you can get an 8-pack of 5"x5", 64F melting-point inserts for $20 + $8 shipping. Or you can get strips of 5, slightly smaller, 60degF pads at mycoolingstore, for $10 each plus $5 flat-rate shipping. Please let me know what you decide. I too will be in the market for replacement pads in a couple months when it warms up here in Pennsylvania...
 

--Dean


There will never be peace in the world while there are animals in our bellies.

#32 Gordo

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Posted 03 February 2016 - 10:41 PM

Techkewl vest arrived today, made it my profile pic, haha.  I already love this thing, its going to be great when the temps warm up.  Seems to hold a very pleasant, steady cool temp but not so cold that its annoying.  I think they use some type of paraffin for the PCM, but I'm wondering if coconut oil would do the job?

 

This is actually an environmentally friendly, highly efficient way to cool people in general (as opposed to cooling an entire house or building all Summer long).  I've also been experimenting with the house temps for fun when the family is not here.  I'm fine down to about 62F in a t-shirt, but any lower gets irritating.  And even the low 60's disrupted my sleep when I tried sleeping with only light cover (I woke up numerous times feeling like I wanted to grab a heavy blanket.  Just wanted to determine my lower limits, I'm not crazy enough keep myself annoyingly cold all the time.  I actually like cooler temps in general, I find it pleasant.



#33 Dean Pomerleau

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Posted 04 February 2016 - 11:32 AM

Gordo,

 

Techkewl vest arrived today, made it my profile pic, haha. 

 

Great picture of you and your cooling vest. Thanks for sharing it! I look forward to getting my own when it becomes necessary here in Pennsylvania. It looks like a good fit.

 

How big are you, and what size did you get? The M/L version I presume?

 

How long does the cooling effect last before a recharge is required and how long does it take to recharge the inserts in the freezer?

 

I think they use some type of paraffin for the PCM, but I'm wondering if coconut oil would do the job?

 
I suspect coconut oil (with a melting point of 77F) would work, perhaps mixed with olive (21F) or peanut oil (37F) to bring down the melting point, and the price!
 
Here is what I might do, if I decide I don't want to spring for a second set of OEM inserts from Techkewl, or from one of the other makers of inserts linked to above:
  • Put the right volume of a mixture of oils into ziplock sandwich bags.
  • Put the sandwich bags flat in the freezer to get them to solidify into the right shape.
  • Once solidified, remove the slugs of solid oil from the sandwich bags and vacuum seal them into durable freezer storage bags of the right size.

The freezer bags that come with vacuum sealer machines are quite rugged, and the vacuum seal is permanent (unlike sandwich bags), so I wouldn't worry (as much) about them leaking, especially after many freeze/thaw cycles.

 

I actually like cooler temps in general, I find it pleasant.

 

Interestingly, I too am experiencing a growing preference for cold conditions. Yesterday I went on my weekly excursion from my house (to grocery shop and get the tube replaced on my stationary bike). It was a unseasonably mild day in PA, about 55F. Driving along in the enclosed car seemed too warm (even with the heat off) so I opened the windows while I drove. It felt very refreshing and invigorating. I suspect it may be a sign of cold adaptation via the synthesis of brown (or beige) adipose tissue via the combination of cold exposure [1] and exercise [2][3].

 

I'm no Wim Hof (aka the Iceman) yet, but I may be getting there.  :)xyz

 

14374638202.jpg

 

----------

[1] Diabetes. 2014 Nov;63(11):3686-98. doi: 10.2337/db14-0513. Epub 2014 Jun 22.

 

Temperature-acclimated brown adipose tissue modulates insulin sensitivity in
humans.
 
Lee P(1), Smith S(1), Linderman J(1), Courville AB(2), Brychta RJ(1), Dieckmann
W(3), Werner CD(1), Chen KY(1), Celi FS(4).
 
 
In rodents, brown adipose tissue (BAT) regulates cold- and diet-induced
thermogenesis (CIT; DIT). Whether BAT recruitment is reversible and how it
impacts on energy metabolism have not been investigated in humans. We examined
the effects of temperature acclimation on BAT, energy balance, and substrate
metabolism in a prospective crossover study of 4-month duration, consisting of
four consecutive blocks of 1-month overnight temperature acclimation (24 °C
[month 1] → 19 °C [month 2] → 24 °C [month 3] → 27 °C [month 4]) of five healthy 
men in a temperature-controlled research facility. Sequential monthly acclimation
modulated BAT reversibly, boosting and suppressing its abundance and activity in 
mild cold and warm conditions (P < 0.05), respectively, independent of seasonal
fluctuations (P < 0.01). BAT acclimation did not alter CIT but was accompanied by
DIT (P < 0.05) and postprandial insulin sensitivity enhancement (P < 0.05),
evident only after cold acclimation. Circulating and adipose tissue, but not
skeletal muscle, expression levels of leptin and adiponectin displayed reciprocal
changes concordant with cold-acclimated insulin sensitization. These results
suggest regulatory links between BAT thermal plasticity and glucose metabolism in
humans, opening avenues to harnessing BAT for metabolic benefits.
 
PMCID: PMC4207391
PMID: 24954193
 

[2] Diabetes. 2015 Jul;64(7):2361-8. doi: 10.2337/db15-0227. Epub 2015 Jun 7.

 
Exercise Effects on White Adipose Tissue: Beiging and Metabolic Adaptations.
 
Stanford KI(1), Middelbeek RJ(2), Goodyear LJ(3).
 
Author information: 
(1)Section on Integrative Physiology and Metabolism, Joslin Diabetes Center,
Boston, MA Department of Medicine, Brigham and Women's Hospital, Harvard Medical 
School, Boston, MA. (2)Section on Integrative Physiology and Metabolism, Joslin
Diabetes Center, Boston, MA Department of Medicine, Brigham and Women's Hospital,
Harvard Medical School, Boston, MA Division of Endocrinology, Diabetes and
Metabolism, Beth Israel Deaconess Medical Center, Boston, MA. (3)Section on
Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School,
Boston, MA laurie.goodyear@joslin.harvard.edu.
 
Erratum in
    Diabetes. 2015 Sep;64(9):3334.
 
Regular physical activity and exercise training have long been known to cause
adaptations to white adipose tissue (WAT), including decreases in cell size and
lipid content and increases in mitochondrial proteins. In this article, we
discuss recent studies that have investigated the effects of exercise training on
mitochondrial function, the "beiging" of WAT, regulation of adipokines, metabolic
effects of trained adipose tissue on systemic metabolism, and depot-specific
responses to exercise training. The major WAT depots in the body are found in the
visceral cavity (vWAT) and subcutaneously (scWAT). In rodent models, exercise
training increases mitochondrial biogenesis and activity in both these adipose
tissue depots. Exercise training also increases expression of the brown adipocyte
marker uncoupling protein 1 (UCP1) in both adipose tissue depots, although these 
effects are much more pronounced in scWAT. Consistent with the increase in UCP1, 
exercise training increases the presence of brown-like adipocytes in scWAT, also 
known as browning or beiging. Training results in changes in the gene expression 
of thousands of scWAT genes and an altered adipokine profile in both scWAT and
vWAT. Transplantation of trained scWAT in sedentary recipient mice results in
striking improvements in skeletal muscle glucose uptake and whole-body metabolic 
homeostasis. Human and rodent exercise studies have indicated that exercise
training can alter circulating adipokine concentration as well as adipokine
expression in adipose tissue. Thus, the profound changes to WAT in response to
exercise training may be part of the mechanism by which exercise improves
whole-body metabolic health.
 
© 2015 by the American Diabetes Association. Readers may use this article as long
as the work is properly cited, the use is educational and not for profit, and the
work is not altered.
 
PMCID: PMC4477356 [Available on 2016-07-01]
PMID: 26050668
 
-------
[3] Ann Nutr Metab. 2015;67(1):21-32. doi: 10.1159/000437173. Epub 2015 Jul 25.

Role of Exercise in the Activation of Brown Adipose Tissue.

Sanchez-Delgado G(1), Martinez-Tellez B, Olza J, Aguilera CM, Gil Á, Ruiz JR.

Author information:
(1)PROFITH 'PROmoting FITness and Health Through Physical Activity' Research
Group, Department of Physical Education and Sport, Faculty of Sport Sciences,
University of Granada, Granada, Spain.

BACKGROUND: The energy-burning capacity of brown adipose tissue (BAT) makes it an
attractive target for use in anti-obesity therapies. Moreover, due to its ability
to oxidize glucose and lipids, BAT activation has been considered a potential
therapy to combat type 2 diabetes and atherogenesis.
SUMMARY: BAT is mainly regulated by the sympathetic nervous system (SNS); yet,
recent findings have shown a group of novel activators that act independently of
the stimulation of the SNS such as cardiac natriuretic peptides, irisin,
interleukin-6, β-aminoisobutyric acid and fibroblast growth factor 21 that could
influence BAT metabolism. Several strategies are being examined to activate and
recruit BAT with no side effects. In this review, we postulate that exercise
might activate and recruit human BAT through the activation of SNS, heart and
skeletal muscle.
KEY MESSAGES: Epidemiological and well-designed exercise-based randomized
controlled studies are needed to clarify if exercise is able to activate BAT in
humans.

© 2015 S. Karger AG, Basel.

PMID: 26227180


There will never be peace in the world while there are animals in our bellies.

#34 Dean Pomerleau

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Posted 05 February 2016 - 03:04 AM

All,

 

Even the Weather Channel is getting on the cold exposure bandwagon - recommending in this video that you sleep in a cool bedroom in order to increase your level of "healthy brown fat".

 

--Dean


There will never be peace in the world while there are animals in our bellies.

#35 AlPater

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Posted 05 February 2016 - 02:27 PM

 
Science News from research organizations
Brown fat responsible for heart disease-related deaths in cold winter months
Date: July 2, 2013
 
Summary:
 
More people die from heart-disease during the winter months, and according to a new study, the increase in mortality is possibly due to the accelerated growth of atherosclerotic plaque in the blood vessels caused by the activation of brown fat by the cold.
 
FULL STORY
 
More people die from heart-disease during the winter months, and according to a new study published in the journal Cell Metabolism, the increase in mortality is possibly due to the accelerated growth of atherosclerotic plaque in the blood vessels caused by the activation of brown fat by the cold.
 
It has long been known that the number of deaths from cardiovascular diseases increases during the winter. It has been speculated that this might be the result of over-exertion while shovelling snow and a general decrease in physical activity, although the underlying mechanisms have been unclear. The present study, which has been conducted by researchers at Karolinska Institutet, and Linköping University in Sweden, and three universities in China, demonstrates a new principle by which the cold increases the risk of atherosclerosis.
 
The researchers conducted their study on a strain of mice genetically modified with a propensity for atherosclerosis. Mice, like humans, have both white and brown body fat. Normal rolls of fat consist mainly of white fat, which is a repository of surplus calories; brown adipose tissue, on the other hand, can convert fat into heat. This heat-generation process is activated by cold temperatures and has been considered beneficial to the health since it can reduce the amount of unnecessary white adipose tissue in the body.
 
"At first, we thought that the cold activation of brown fat would only make the mice thinner and healthier," says Yihao Cao at the Department of Microbiology, Tumour and Cell Biology at Karolinska Institutet, and the Department of Medicine and Health at Linköping University. "Instead, we found that they ended up having more fat stored in the blood vessels. This came as a surprise and was the opposite of what we thought would happen."
 
It turned out that exposure to low temperatures accelerated the formation of atherosclerotic plaque in the mice, which can cause myocardial infarction and brain haemorrhaging. Moreover, the cold made the plaque less stable, and if such plaque ruptures, stored fat can leak into the blood, blocking vessels in the heart and brain. The cold-activated breakdown of fatty acids in the mice's brown fat led to the accumulation of low-density lipoproteins (LDL) in the blood and an increase in fat storage in the plaque.
 
"If this is also true for humans, it might be wise to recommend that people who suffer from cardiovascular disease should avoid exposure to the cold and to put on warm clothes when they are outside during the winter," says Professor Yihai Cao.
 
The researchers hope to be able to extend their work on mice to studies on humans.
 
"It would be an extremely important discovery if we found this to be the case in humans too," says Professor Yihai Cao. "Brown adipose tissue is affected not only by the cold -- its activation can also be blocked by several existing drugs, something that we would like to study further."
 
It was long believed that people only have white fat tissue, and that brown fat was only found in certain mammals, such as rodents; as it is, research has shown that the human body contains two types of brown adipose tissue. Recently, researchers from Sweden and elsewhere has revealed that infants at least have the typical brown, heat generating fat tissue, a discovery that raised hopes about finding new means by which to treat obesity. The present study, however, suggests that activating brown fat to reduce bodyweight can be risky in combination with some form of cardiovascular disease.
 
Story Source:
 
The above post is reprinted from materials provided by Karolinska Institutet. Note: Materials may be edited for content and length.
 
Journal Reference:
 
Cold exposure promotes atherosclerotic plaque growth and instability via UCP1-dependent lipolysis.
Dong M, Yang X, Lim S, Cao Z, Honek J, Lu H, Zhang C, Seki T, Hosaka K, Wahlberg E, Yang J, Zhang L, Länne T, Sun B, Li X, Liu Y, Zhang Y, Cao Y.
Cell Metab. 2013 Jul 2;18(1):118-29. doi: 10.1016/j.cmet.2013.06.003.
PMID: 23823482 Free PMC Article
 
Abstract
 
Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown. Here, we show that the cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development of atherosclerotic lesions in mice. In two genetic mouse knockout models (apolipoprotein E(-/-) [ApoE(-/-)] and LDL receptor(-/-) [Ldlr(-/-)] mice), persistent cold exposure stimulated atherosclerotic plaque growth by increasing lipid deposition. Furthermore, marked increase of inflammatory cells and plaque-associated microvessels were detected in the cold-acclimated ApoE(-/-) and Ldlr(-/-) mice, leading to plaque instability. Deletion of uncoupling protein 1 (UCP1), a key mitochondrial protein involved in thermogenesis in brown adipose tissue (BAT), in the ApoE(-/-) strain completely protected mice from the cold-induced atherosclerotic lesions. Cold acclimation markedly reduced plasma levels of adiponectin, and systemic delivery of adiponectin protected ApoE(-/-) mice from plaque development. These findings provide mechanistic insights on low-temperature-associated cardiovascular risks.
 
"These findings are consistent with the decrease of body weight and body mass index (BMI) due to a high metabolic rate during cold acclimation (Figure S1C). The cold-triggered high metabolic rate and lipolysis are likely to alter blood lipid profiles. Indeed, the level of plasma triglyceride (TG) was significantly decreased (Figure 1H), further validating the cold-induced body weight loss. Conversely, levels of cholesterol, LDL cholesterol, and glycerol were increased by 2- to 3-fold".


#36 Dean Pomerleau

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Posted 05 February 2016 - 04:28 PM

Thanks Al,

 

I noticed the mouse study that is referenced in the article you posted (PMID 23823482) and linked to it at the bottom of my brain dump on cold exposure research, as the one potential negative side effect of cold exposure I've come across.

 

But I think it's worth noting that the observed increased risk of unstable atherosclerotic plaque formation was in genetically messed up mice which are unusually prone to CVD as a result of knocking out the gene for APoE (which processes cholesterol) or knocking out the gene for the LDL receptor itself, plus they were fed a high fat diet to make sure to induce high cholesterol and obesity prior to, and during, the cold exposure. From the study's visual abstract:

 

oMm5xb1.png

 

it is apparent that cold exposure results in increased burning of fat, i.e. converting it into free fatty acids and glycerol, an effect that is by now so well established that even the Weather Channel recognizes it :)xyz.

 

In genetically aberrant animals (or probably people!) who are naturally inclined towards a high levels of serum LDL cholesterol when they burn fat, cold exposure may result in an increase in LDL cholesterol, and increased plaque formation.

 

But it doesn't appear like it's the "fault" of cold exposure per se, but simply a result of burning more fat. And it appears to be mediated by elevated serum cholesterol, so those of us who have good (or in Saul's case 'stellar'  :)xyz) cholesterol levels, this potential downside of cold exposure shouldn't be an issue.

 

But it will be worth monitoring cholesterol level during cold exposure to make sure it doesn't go up dramatically. I'm donating blood in a couple weeks, and will get a (free) serum cholesterol test as a perk. I'll see where my LDL is at that time.

 

--Dean


There will never be peace in the world while there are animals in our bellies.

#37 AlPater

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Posted 06 February 2016 - 01:57 PM

Thanks, Dean.  They were messed up subjects but there would be no results, not even negative ones, using healthy ones.  Wild type subjects fed good diets would have no chance of seeing if there was an effect.  Did you also note that the subjects were "stabbed in the back" so to say by the involvement of your good guy, UCP1?



#38 Dean Pomerleau

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Posted 06 February 2016 - 02:12 PM

Al,

 

Not for the first time I find you language rather cryptic. I'll try to decipher. Correct me if I've misinterpreted your meaning.

 

They were messed up subjects but there would be no results, not even negative ones, using healthy ones.  Wild type subjects fed good diets would have no chance of seeing if there was an effect.

 

If you mean no results in terms of elevated LDL and plaque formation if the mouse subjects had normal genes, were eating a good diet and weren't obese, I concur. That was what I was trying to express in my post above. During weight loss via burning fat, a person's (or a mouse's) cholesterol can rise as the fat is broken down and circulated around the body. If one is susceptible to elevated LDL and plaque formation, as these mice were, plaques can & will form.

 

Did you also note that the subjects were "stabbed in the back" so to say by the involvement of your good guy, UCP1?

 

What I'm suggesting is that rather than "stabbing them in the back", UPC1 helped the mice to burn the excess fat they were carrying. It was their mutant cholesterol processing genes combined with a diet high in saturated fat that "stabbed them in the back", resulted in elevated LDL cholesterol and plaque formation during the cold-induced weight loss.

 

By analogy - exercise can help people burn fat & lose weight. But it can also over-stress their cardiovascular system by raising blood pressure, heart rate, etc if they are out of shape, possibly resulting in a heart attack. You wouldn't blame the exercise per se for the heart attack.

 

But again, as I said in the previous post - if someone is experimenting with cold exposure, it's worth keeping an eye on your cholesterol level.

 

--Dean


There will never be peace in the world while there are animals in our bellies.

#39 Gordo

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Posted 07 February 2016 - 07:46 AM

Great picture of you and your cooling vest. Thanks for sharing it! I look forward to getting my own when it becomes necessary here in Pennsylvania. It looks like a good fit.

 

How big are you, and what size did you get? The M/L version I presume?

 

How long does the cooling effect last before a recharge is required and how long does it take to recharge the inserts in the freezer?

 
I'm 6' and 148 lbs.  Yes, bought the M/L version.  I would say the panels and vest themselves are sized right, but the adjustment straps are definitely NOT made for CRONies like us, the problem is that they are velcro and you run out of "loops" for your "hooks" if you try to adjust it tight on a skinny body.  I will have to modify the adjustment straps so that I can make it fit snugly.
 
The panels can recharge in a freezer in 45 minutes, however I suspect to get to the point of maximum cold storage (thermal capacity?) it needs at least 2 hours. I'll do some more experiments on that, haven't had time to do much testing yet.  I also haven't had time to properly test how long it can cool for under various conditions.  Many user reports in Amazon reviews say it can cool for hours.  When mine was delivered it was left outside all day in 40 degree temps, so when I opened it, it was already "charged" but maybe not "supercharged" - the cooling packs were solid and white, I wore it for about an hour and at that point they were 90% liquid, so maybe with a proper charge you might get 2 hours of cooling but I'm guessing maybe not even that much.  Still you could probably get by with just 2 sets of cooling packs.
 

 

I think they use some type of paraffin for the PCM, but I'm wondering if coconut oil would do the job?

 
I suspect coconut oil (with a melting point of 77F) would work, perhaps mixed with olive (21F) or peanut oil (37F) to bring down the melting point, and the price!
 

 

Techkewl's MSDS is here:

http://www.techniche...file.html?id=13

 

I found a huge 56oz jar of coconut oil at BJs for just $8.49, I'll be experimenting with that.

bjscocooil.jpg

 

Note: I'm not very concerned about elevating my LDL through cold exposure, but I will definitely monitor that.  My LDL was 50 in my most recent test.


Edited by Gordo, 07 February 2016 - 07:59 AM.


#40 Dean Pomerleau

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Posted 07 February 2016 - 01:23 PM

Gordo,

 

Thanks for the additional details. It's too bad they don't make the vest a little smaller, but I guess we'll have to make due. Regarding the 2-hour charge - that is a little disappointing, but I guess not surprising, since paraffin and oils have only about half the specific heat of water - meaning it only takes half as much energy to raise their temperature.

 

Note: I'm not very concerned about elevating my LDL through cold exposure, but I will definitely monitor that.  My LDL was 50 in my most recent test.

 

You'll have even less reason to worry in about five minutes, when I submit my next post...

 

--Dean


There will never be peace in the world while there are animals in our bellies.





Also tagged with one or more of these keywords: Cold Exposure, Exercise, Fasting, UCPs, UCP1, UCP3, FGF21