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Brown/Beige Adipose Tissue Activation (BAT) via Cold Exposure and Diet for Health and Longevity

bat cold exposure longevity blood glucose

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#1 Gordo

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Posted 13 June 2016 - 06:42 AM


First, I hope I don't come off as shamelessly plugging some other website, especially since I'm new here, but I need to give credit where credit is due, most of what I've learned about this topic came from reading Dean Pomerleau's very long and detailed forum postings at the CR Society.  I'm starting this topic at Longecity as a way of opening up the research, ideas, and experiences to a wider audience in order to potentially improve and share knowledge in this area.  It would be extremely difficult and time consuming for me to completely reproduce or even adequately summarize everything that Dean has amassed on this subject but I will try to give some highlights and then share some details about my own personal experimentation and results.

 

There has been a rapidly growing interest in the scientific community around brown fat (BAT).  Scientific American even published "Supercharging Brown Fat to Battle Obesity" containing a very nice summary of knowledge up to that point in time (2014).  New research in this area is really picking up, with new articles appearing in reputable journals now seemingly on a weekly basis.  Big pharma is scrambling to come up with a pill that can activate BAT, grow BAT, turn white fat into beige or brown fat, etc.  Until such pharmaceuticals exists (if they ever do), there are many lifestyle interventions you can undertake to achieve the health benefits of BAT activation.  I want to emphasize that this has much wider application than just a weight loss tool (which seems to be the focus of most popular press coverage of the subject).

 

In another post, I will talk about specific interventions you can undertake, but to cut to the chase I will just say up front, BY FAR the most effective way to achieve these benefits is via cold exposure (not supplements, exercise, or special foods, although those can help to some degree).

 

Here is a summary of some of the benefits:

 

Fibroblast Growth Factor 21 Production.  FGF-21 has been documented as a pathway to longevity.  Cold exposure (CE) up-regulates circulating fibroblast growth factor 21 (FGF21) in people by 37%, and FGF21 in mice BAT by a factor of 40x. In mice, not just BAT but plasma levels of FGF21 are unaffected by only 6h of cold exposure, but doubles after 24h, and triples after 30 days of CE:  So what good is FGF21?  Transgenic mice that overexpress FGF21 lived 40% longer than controls without the mutation, despite the FGF21-mutant mice eating a bit more than the normal mice. Cold exposure → ↑ BAT → ↑ FGF21 → ↑ longevity), but it shows obesity-independent benefits of cold exposure & BAT.  Interestingly, in addition to (or by way of) extending lifespan, it is well known that FGF21 improves insulin sensitivity & glucose metabolism

Adiponectin Production - Like calorie restriction, cold exposure increases adiponectin levels. Two hours of cold exposure resulted in a 70% increase in circulating adiponectin in adult men. Furthermore, centenarians and their offspring have been found to have genetics that boost adiponectin, and they have higher circulating adiponectin, suggesting a link between longevity and adiponectin production and/or secretion.   The same thing was found in a group of centenarian women - "As compared to BMI-matched [young, ~28 year-old] female controls, female centenarians had significantly higher plasma adiponectin concentrations. In addition, high concentrations of plasma adiponectin in centenarians was associated with favorable metabolic indicators, and with lower levels of C-reactive protein and E-selectin". For those of us who aren't lucky enough to have adiponectin-boosting genes, we can increase adiponectin levels via CR, cold exposure, or both. This video illustrates how wearing a cooling vest (Cool Fat Burner in this case) for two hours raises a cold-adapted person's adiponectin level by a whopping 62%! 

Irisin Production - Both cold exposure and exercise increase circulating irisin. Irisin improves insulin sensitivity, increases bone quality and quantity, is involved in the building of lean muscle mass, and helps reduce obesity by converting white fat to brown fat. In short, it appears CE provides many of the same benefits of exercise, including raising irisin.Healthy centenarians are characterized by increased serum irisin levels, whereas levels of this molecule were found to be significantly lower in young patients with myocardial infarction. These researches note: "Our findings may prompt further research into the role played by irisin not only in vascular disorders but also in life span modulation."

SIRT1 Pathway Activation - SIRT1 is upregulated by calorie restriction (CR), and is thought to be one of the important pathways through which CR extends lifespan. While the lifespan effects of SIRT1 in mammals are somewhat controversial, transgenic mice that over express SIRT1 have increased lifespan and genetic mutations that result in elevated SIRT1 levels in people are associated with increased human longevity. SIRT1 (and the other sirtuins) have many metabolic effects, but an important one for improving health and longevity is the fact that SIRT1 increases insulin sensitivity and glucose control in skeletal muscles, triggers the browning of white fat and increases BAT activity, which is fully reversed by thermoneutral housing. Mice partially lacking SIRT1 due to a genetic mutation experience BAT degeneration, reduced thermogenesis, increased inflammation and develop obesity and insulin resistance as a result.  It's not just CR that up-regulates SIRT1. Cold exposure increases SIRT1 phosphorylation/activity in both skeletal muscle and BAT, increasing thermogenesis and insulin sensitivity. In short, both CR and CE up-regulate SIRT1, which (may) increase lifespan, at least in part by improving insulin sensitivity in muscles and increasing BAT & BAT activity. 

 

Increased natural killer (NK) cells which boosts the immune system.  Rodent studies have demonstrated that cold exposure results in a dramatic decline in cancer mortality.  Research suggests that reduced cancer mortality as a result of CE is likely a result of active upregulation of immune system function via increased natural killer (NK) cells, triggered by elevated epinephrine and interlukin-6 (IL-6).  This is of particular importance to anyone practicing CR which is known to impair certain aspects of immune function as well as bone density.

 

 

CE/BAT may play an important role in bone health and bone density.

 

 

 

It is interesting to note that the longest-lived small mammals: grey squirrels (24 yrs), bats (30 yrs), and naked mole rats (32 yrs), all have remarkably high levels of BAT and BAT activity.  There seem to be new benefits being discovered almost monthly, the list continues to grow.  I hope the above is enough to spark interest.

 

One aspect of CE I've focused on personally is its mechanism to control/lower blood glucose that is outside of the usual insulin pathway.  That means anyone with impaired insulin function might benefit, however there should also be much broader interest given the research showing elevated blood glucose is associated with most of the leading causes of death and disease today and leads to damage over time of many organs (especially eyes, endothelial/cardiovascular system, and brain) and results in higher levels of advanced glycation end products.

 

At any rate, I have been practicing cold exposure now for about 4 months and I have seen some encouraging results.  I will share my cooling techniques in a separate post.  Here is a sample log showing the glucose control I've been able to achieve:

 

LOG

Started morning with max cold shower (as I now do every morning) at 7:10AM

Had large glass of crushed ice water at 7:45AM

Went out, came back. 9:30AM had another large glass of crushed ice water.

House was 70 degrees all day.  No food or exercise all morning, just mental work (iPad app development).  Focus and mental clarity are stellar, I believe the cold showers help with this.

 

1:55PM fasting blood glucose (BG)=58 mg/dl

1.jpg

(I've seen readings as low as 54, while still feeling great (no hypoglycemic symptoms), never saw such readings before I started cold exposure)

 

Put on techkewl cooling vest and started making lunch at 2:30PM.

techkewl.jpg

(The internet said this would make me cool, haha)

 

3:01PM (final fasted reading) BG=68 mg/dl

2.jpg

Finished preparing nice high GI meal consisting of a carefully measured and weighed:

highgimeal.png

The barley was first milled into "flour" using  a 30 second blend in my blendtec blender (for maximum blood sugar spiking capacity) along with the flax and chia then combined with the almond milk (plus a cup of water) and oats and pressure cooked for 10 minutes at 15PSI. Everything else was added after cooking.

That's 219g of carbs and 82 grams of sugar, including pure liquid sugar in the form of maple syrup.  

 

Breakdown of the macros:

macros.png

 

Pic of meal - can't tell by the pic, but a 1352 calorie bowl of porridge is pretty huge and heavy and would fill almost anyone up:highgimealpic.jpg

 

Started eating at 3:03PM

Drank one cup of crushed ice and water with lemon squeeze while eating.

Finished eating at 3:21PM

3:23PM (2 minutes postprandial) BG=68 mg/dl

3.jpg

3:40PM Had another cup of crushed ice water.

3:43PM (22 minutes postprandial) BG=64 mg/dl

4.jpg

(wow, I was expecting a 20 minute postprandial spike with a high GI meal like this, on the contrary, my BG actually went DOWN)

 

4:09PM (48 minutes postprandial) BG=70 mg/dl

5.jpg

4:35PM (1 hour 14 minutes postprandial) BG=62 mg/dl

6.jpg

5:09PM (1 hour 48 minutes postprandial) BG=76 mg/dl

7.jpg

5:30PM Cooling vest is spent.  Removed.  Had another large glass of crushed ice water.

6:00PM (2 hours 39 minutes postprandial) BG=77 mg/dl (final reading)

8.jpg

 

I am impressed by the BAT induced BG stability. Again I never saw results like this before I started doing CE.

 

 

 


Edited by Mind, 26 June 2016 - 11:16 AM.

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#2 Gordo

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Posted 13 June 2016 - 06:53 AM

I've been doing more rigorous personal experiments on cold exposure and its affect on my blood glucose (a well documented relationship covered in several studies posted in this thread).  Just for some background, I've been rather closely tracking my blood glucose for about 18 months now.  I became interested in this because higher circulating glucose is linked to aging, glycation, and damage to numerous human organs over time.  During that timeframe I've done well over a 100 readings.  Even after going weeks on 100% low GI foods, AND fasting, the lowest reading I ever saw was 67 mm/dL and I put a GREAT deal of effort into even achieving that level.  I use a TRUEResult test meter which has among the best reviews on Amazon (and cheapest test strips!) in case anyone is interested.  I have taken readings with this meter before and after being lab tested, and it was spot on accurate with the lab results, several healthcare companies actually require their diabetic customers to use this meter.  I'm giving you this background because I have been very surprised by the results I am now achieving with CE.  I've only been intentionally doing CE for 5 or 6 weeks, during that time I went from a typical always cold, CR "wimp" to someone who can lay around all day in a cold house wearing nothing but boxers and actually feel hot thanks to thermogenesis (and not only feel an actual burning sensation, but often even sweat without exercising).

 

Below is my log from April 8, 2016... (Note that I never wore a cooling vest AT ALL this time)

LOG

Glucose reading shortly after waking up = 77mg/dL (7:26AM)

1.jpg

Drive kids to school, by now they have learned to bundle up in winter coats despite the fact that Dad is wearing only a t-shirt and shorts, cuz there won't be any heat ;).  41F degree air blowing on me the whole time (I can handle 20's!).  I take my shirt off after dropping off the kids (still seems too socially unacceptable / creepy to go shirtless with the kids in the car), another 30 minutes of 41F degree air (1 hour total) and I'm back at home for a work from home day.  Despite no heating, the house is 65F degrees and will remain exactly that temperature for the rest of the day (I'd prefer it a bit cooler but this will do).  5 hours go by working from home in 65 degrees wearing only boxers and socks (at least one study I read used 66F degree air with beneficial results).  That's 6 hours total of mild CE.

I generally only eat between 12PM and 7PM.

I have found that CE+fasting past a normal eating time results in surprisingly low blood glucose levels (some studies have shown an interesting glucose lowering effect from thermogenesis in anticipation of eating, almost like salivating).   Importantly, these low levels HAVE NOT resulted in hypoglycemic symptoms (I felt great all day today, thinking clearly, getting work done, etc).

Fasting slightly past normal meal time, I take a reading: 63mg/dL (12:31PM)

2.jpg

Mild (65F) CE continues through entire day.  I prepare what I would consider a typical, CRON, large meal:

meal.jpg

For some reason I missed one item above, for the sake of completeness and because red chili peppers have been shown to synergistically (with CE) boost thermogenesis, here it is:

pepper.jpg

Meal Stats:

mealinfo.png

1410 calories of pure goodness!  I finish eating all of the above, at 1:45PM.

10 minutes post prandial = 75mg/dL (1:55PM)

3.jpg

30 minutes post prandial = 67mg/dL (2:16PM)

4.jpg

I wanted to test the idea that maybe a "cold finger" or "bad circulation" could cause lower readings - so at this point I did a high intensity cardio workout (running up and down stairs wearing a 40 lbs. weight vest for a few minutes), then I ran my hand under hot water to warm it up.  I thoroughly dried hands/fingers and took another reading.

40 minutes post prandial, post exercise, post hand warming = 59mg/dL!  (2:25PM)

5.jpg

The low readings don't seem to have anything to do with circulation or cold fingers.

I want to note again, I was feeling good this whole time, no hypoglycemic symptoms whatsoever.

There seems to be potential for even mild CE to do good things for health and longevity.  

I feel like there is some connection between meal content (carbs/sugar vs. fat) and/or exercise that contributes to maximal thermogenesis.  Even an hour after my little "stair run", just sitting in a cool room -- my neck, collarbone area, ribs, and thighs feel like they are burning up, definitely "feels" like peak thermogenesis for the day right now (3-4PM).

By 5:22PM I'm back up to 68:

6.jpg

 

 

 

Areas for further research:

  • Best way to "ignite" thermogenesis (Best temps? How long? Continuous or intermittent? How does food affect it and what foods are best? How does exercise affect and what type/duration?) 
  • Are these readings in the 50's accurate?  The next time I get lab tested I will try to go when my meter has a reading in the 50's to confirm.  Many people would experience hypoglycemic symptoms at these levels but that is not the case for me, is there something interesting going on to account for that with regards to the CE processes?

 

Also I want to reiterate one thing - some people that do CR seem to think they are getting CE because they feel cold all the time or have a low measured body temperature.  Feeling cold is not evidence that you are "doing CE", in fact it probably indicates that you aren't.  Until you feel the burn of wonderful thermogenesis while sitting naked in a cold room, you haven't experienced CE!   biggrin.png

 


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#3 Gordo

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Posted 13 June 2016 - 07:03 AM

Along the lines of practical application and contraindications...

I think if CE is a detriment to your sleep, is causing any physical problems (cold burns/frost bite, certain hypothermia symptoms: irritability, combativeness, confusion, delirium, slow reflexes, seizures, stupor, coma) you are obviously going way overboard.  If you are doing this right, your body is going to produce its own heat, and lots of it, so that your core temperature remains steady instead of dropping (requiring extra calories in the process).  If you are seeing excessively low body temperatures I would speculate that you are either not eating enough calories, possibly not eating enough fat (I get 30-40% of my calories from fat), or do not have enough adipose (and possibly muscle) tissue to begin with to support thermogenesis (may require higher BMI).

 

Some studies have noted beneficial effects from as little as 2 hours a day at just 66 degrees F exposure.  The cooling vest I use has a phase change temp of 58 degrees and I think that is just about perfect honestly.  There is a more extreme vest out there called the "Cool Fat Burner", I don't own one, and it might be over the top for many people, but if you are looking for more serious cooling that could be your best bet.  The guy who created it also maintains a nice science page you may want to check out.

 

More tips on "how to stay cool when it's hot out"

 

Now that the temps are rising where I live, I've been experimenting with various ways to stay cooler without blasting air conditioning all the time.  These are also low cost things you can do if you don't own a cooling vest.

 

  • Take cold showers.  I can't believe it took me so long to discover this, but cold showers are amazing.  A good way to get started is by getting in with lukewarm water, then slowly make it colder taking it as far as you can handle until you can take 100% cold water.  The first couple times I did "full cold" it was a real shock to my system causing involuntary hyperventilation, discomfort, and probably spiking blood pressure, but it only took a few times before I got acclimated to it, now I can step directly into a full cold shower with no warm up and minimal shock factor.  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!  If you google: cold shower norepinephrine you will get a taste for the fascinating research that has been done with this.  Note: If for some reason your tap water isn't cold, a good alternative is to fill your bath with water and add ice, no reason to go below about 55 degrees though.  Research has shown that immersion in 57 degree water results in:
    "increased metabolic rate (by 350%), heart rate and systolic and diastolic blood pressure (by 5%, 7%, and 8%, respectively). Plasma noradrenaline and dopamine concentrations were increased by 530% and by 250% respectively, while diuresis increased by 163% (more than at 32 degrees C). Plasma aldosterone concentrations increased by 23%. Plasma renin activity was reduced as during immersion in water at the highest temperature. Cortisol concentrations tended to decrease. Plasma adrenaline concentrations remained unchanged." 

     

     As a bonus, it is nearly impossible to be or become depressed when you are following a cold shower protocol due to the boost it causes in endorphins, noradrenaline, and dopamine. 

TIP: Let the cold water hit your face alone at first, this activates your dive reflex which in turn prepares your body for full cold water immersion and less shock.

 

 

  • Drink ice water with crushed ice.  It is possible to be in a 75 degree room without a cooling vest, and still have goose bumps on your arms, just from drinking crushed ice.  Note: I also tried swallowing bigger ice cubes just to see if it was viable -- I do NOT recommend this, they sometimes get stuck "on the way down" resulting in intense pain, and sometimes brain freeze as you try to line it up just right, definitely not worth it.  One doctor has even been promoting what he calls "The Ice Diet" which is an interesting read.  Eating a liter of ice per day may burn over 100 extra calories although this is disputed.

 

  • Eat frozen superfoods.  Things like frozen berries not only taste great, but promote great health.  Frozen foods can even pack more nutrients than their fresh counterparts.  When I find the best tasting, in season, fresh produce that freezes well, I stock up the deep freezer.  I was really enjoying some amazing frozen Chilean blueberries yesterday.  I'm going to go get some more right now...

 

  • Use an ice bag.  I own 4 of them, bought them for just $5 (from Aldi).  Check the reviews on Amazon, people love these things.  They can be placed directly on your clavicle area or rotated around to various brown fat hot spots.  These get far colder than my cooling vest (but generally only stay cold for an hour or less).

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#4 Gordo

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Posted 13 June 2016 - 07:10 AM

Here is Dean Pomerleau's latest list of modifiable and [nonmodifiable] factors associated with increased brown/beige adipose tissue and/or thermogenesis

  • Cold exposure - by far the best BAT inducer/activator
  • Spicy / pungent foods, herbs & supplements - capsaicin / chilli peppers, curcumin / turmeric root, menthol/mint/camphor, oregano, cloves, mustard, horseradish/wasabi, garlic, onions
  • Sulforaphane-rich foods - Broccoli, brussels sprouts, cabbage
  • Arginine-rich foods - Good vegan sources include seeds (esp. sesame, sunflower & pumpkin), nuts (esp. almonds and walnuts) and legumes (esp. soy, lupin & fava beans and peas)
  • Healthy Fats - Olive Oil / MUFA-rich diet, DHA / EPA / fish-oil
  • Nitrate-rich foods - beets, celery, arugula, and spinach
  • Other foods - Apples / apple peels / ursolic acid; Citrus fruit / citrus peels / limonene; Honey / chrysin
  • Beverages - green tea, roasted coffee, red wine, cacao beans / chocolate
  • Drugs / Supplements - metformin, caffeine, creatine, nicotinamide riboside (NAD), resveratrol, ginseng,cannabidiol / hemp oil / medicinal marijuana
  • Low gluten diet
  • Methionine restriction - Reduce animal protein. Soy is low in methionine and high in arginine.
  • Low protein diet
  • Fasting
  • Exercise
  • Acupuncture - locations Zusanli (foot - ST36) and Neiting (lower leg - ST44) 
  • Whole body vibration therapy
  • Avoid obesity/overweight
  • [Being naturally thin - high metabolic rate]
  • [Being younger]
  • [Being female]
  • [Ethnicity - having cold-climate ancestors]

 

Isn't it interesting how so many of the foods linked to BAT activation have for many years (centuries) been noted for their health promoting effects?  BAT is starting to look like some kind of unifying tour de force for exceptional health and longevity.

 

Regards,

Gordo

 


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#5 Gordo

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Posted 13 June 2016 - 07:24 AM

It seems like I can eat almost anything now without spiking my blood glucose.  I find the "cool fat burner" guy mentioned previously to be hilarious (and goofy), but also inspirational.  That guy has done quite a lot of personal experimentation and has created many interesting videos.  His personal experiments are not scientifically rigorous, however many studies published in reputable peer reviewed journals seem to back up the things that he reports.  Anyway, in one of his videos he mentions binging on junk food including multiple slices of pie plus 18 scoops of ice cream (!) to demonstrate the impact of BAT activation on blood glucose - 1.5 hours after this binge, his blood glucose was only 90, and his fasting number the next morning was 66!  I immediately thought that if this were true, it could become a serious health intervention and may even change the way people following a longevity focused lifestyle do things.  

 

So anyway, after building up my own BAT levels and becoming cold adapted, I really wanted to put my body to the test. As circumstances would have it, I ended up at a "Friendly's" with my family.  I'm not recommending this to anyone else, but I sacrificed myself for science so you guys wouldn't have to, and ate one of their Veggie burgers first, followed by one one of these:

cb4043b532b5ec386e799564ee0c9581.jpg

 

  • Reese's Pieces Sundae Calories:930
  • Fat Calories:480
  • Total Fat (g):53
  • Saturated Fat (g):26
  • Cholesterol (mg):90
  • Sodium (mg):360
  • Total Carbohydrates (g):95
  • Sugars (g):67
  •  

The veggie burger stats:

  • Total Calories:561
  • Fat Calories:244
  • Total Fat (g):27
  • Saturated Fat (g):6
  • Cholesterol (mg):10
  • Sodium (mg):834
  • Total Carbohydrates (g):66
  • Sugars (g):10
  • Dietary Fiber (g):5
  • Protein (g):13

After that I wore the cooling vest for 3 hours (no exercise) then tested my blood glucose.  It was 76 mm/dl.  The next morning reading was 79. 

I'm interested in others' self experimentation results and experiences with cold exposure...

Regards,

Gordo

 


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#6 drew_ab

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Posted 13 June 2016 - 01:44 PM

It's incredible that something potentially so powerful hasn't gained more traction.  Thank you so much for sharing your detailed log.  It was incredibly enjoyable to read and I hope others here take the time to read it.  I wonder how cold exposure works when only applied to parts of the body.  For example, I walk my dog every morning for 30 minutes and the air temperature is 10'F to 40'F for 8-9 months a year.  I do well with shorts on in this weather (and a t-shirt/sweater) and wonder if I am experiencing some level of CE.  I guess one way to find out would be to do some glucose readings.

 

I recently started chomping on lots of crushed ice and noticed that I have to be careful how I chew, since it feels like it might be hard on my teeth/gums.  Have you noticed anything here?  Interestingly I've been inadvertently doing many of the things you mentioned on the list for over 5 years now. 

 

Related, I used to feel bad about keeping my dog housed in a 63'F house all day while at work (it saves lots on the heating bill), but perhaps I'm actually doing him a longevity favour!

 

Dr. Rhonda Patrick and Ray Cronise have an incredible podcast which covers some of what you are experiments with.

 

 

 


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#7 deanp

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Posted 13 June 2016 - 04:47 PM

Wow Gordo,

 

You've done a terrific job condensing the mountain of material we've compiled over on the CR Society Forums thread on cold exposure documenting the benefits of brown/beige adipose tissue, and how to boost them - particularly via cold exposure, but also diet, certain supplements/nutraceuticals and lifestyle interventions. I too hope it will pique the interest of LongeCity folks. As you say, there is a lot more to its benefits than merely weight loss. 

 

Let me try to amplify just one of the points you mention:

 

It is interesting to note that the longest-lived small mammals: grey squirrels (24 yrs), bats (30 yrs), and naked mole rats (32 yrs), all have remarkably high levels of BAT and BAT activity. 

 

I too found this correlation between BAT and lifespan in small mammals pretty compelling. Here are the discussions about how brown fat plays into the longevity of these three extraordinary species - grey squirrels, bats, and naked mole rats. And the benefits of cold exposure and BAT not just isolated to these three long-lived species. This study [1] analyzed data from both controlled laboratory experiments and free-living populations of many species that spanned a wide range of latitudes, to see how longevity within-species correlated with climate. Here is what they did and what they found:

 

We compiled data for 30 species under laboratory conditions and for 67 free-living species (1,081 populations). These data represent 4 phyla and 23 orders from around the globe. The dataset contained representatives from terrestrial, freshwater, and marine environments, and of widely different average longevities [minimum average lifespan 11.6 d (Acartia tonsa), maximum 190.0 yrs (Margaritifera margaritifera)]. Latitude and lifespan were positively correlated in 85% of the species, although the relationship was statistically significant in only 39% of the cases. It is worth noting that under a null model without a latitudinal gradient in lifespan, the chances of obtaining 85% positive slopes are exceedingly small (χ2 = 27.597, P < 0.0001). Moreover, for all species with significant regressions, lifespan increased with latitude. As discussed below, it appears that much of this latitudinal variation may be explained by temperature using the MTE.

 

To summarize, in species that span a wide range of latitudes, the within-species longevity is pretty strongly correlated with how far north (or south, in the southern hemisphere) an individual lives. That is, cooler environments → increased lifespan across a huge range of land, freshwater and marine species. Although less compelling because it wasn't an interventional study, the wide range of species which exhibited a longer lifespan in cold climates is suggestive, particularly when linked with the evidence discussed here that people's HbA1c improves in winter months.

 

Overall, as you describe so well in your opening posts, the scientific evidence and our personal experience seem to show dramatic health and (potentially) longevity benefits may be possible as a result of cold exposure and other interventions to boost brown & beige adipose tissue. 

 

--Dean

 

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

[1] Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13860-4. doi:
10.1073/pnas.0900300106. Epub 2009 Jul 30.
 
Latitudinal variation in lifespan within species is explained by the metabolic
theory of ecology.
 
Munch SB(1), Salinas S.
 
 
Many ectotherms exhibit striking latitudinal gradients in lifespan. However, it
is unclear whether lifespan gradients in distantly related taxa share a common
mechanistic explanation. We compiled data on geographic variation in lifespan in
ectotherms from around the globe to determine how much of this intraspecific
variation in lifespan may be explained by temperature using the simple
predictions of the metabolic theory of ecology. We found that the metabolic
theory accurately predicts how lifespan varies with temperature within species in
a wide range of ectotherms in both controlled laboratory experiments and
free-living populations. After removing the effect of temperature, only a small
fraction of species showed significant trends with latitude. There was, however,
considerable residual intraspecific variation indicating that other, more local
factors are likely to be important in determining lifespan within species. These
findings suggest that, given predicted increases in global temperature, lifespan
of ectotherms may be substantially shortened in the future.
 
PMCID: PMC2728985
PMID: 19666552
 

Edited by deanp, 13 June 2016 - 04:49 PM.

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#8 Gordo

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Posted 13 June 2016 - 07:58 PM

Dean -- thanks for describing the compelling data on longevity across such a large swath of species as it relates to cold exposure.

 

Drew -- Yes, you do need to take some care when consuming ice.  Ideally you want to use crushed ice that is broken up enough already that you can just swallow the pieces whole without much if any chewing.  Ice can chip teeth, I suppose it could potentially cut into other mouth parts tho I've never had either problem.  You can also let bigger ice cubes/chunks sit for a while in water which will weaken them making them easy to chew if necessary.

 

 

 

I wonder how cold exposure works when only applied to parts of the body.[4] Obesity (Silver Spring). 2011 Jan;19(1):13-6. doi: 10.1038/oby.2010.105. Epub

Indeed it does seem to work.  This study simply cooled fat mens' legs with ice and this resulted in supraclavicular BAT activation (in other words, no where near where they were doing the cooling).  I don't think much research has been done yet on the BEST methods of cooling for BAT activation but I get the sense that the majority seems to think direct cooling of actual BAT tissue is most effective (would be nice to see a study prove this!).


 

 

 

Thirteen healthy male volunteers aged 20-28 years underwent FDG-PET after 2-h cold exposure at 19 °C
with light-clothing and intermittently putting their legs on an ice block. When
exposed to cold, 6 out of the 13 subjects showed marked FDG uptake into adipose
tissue of the supraclavicular and paraspinal regions (BAT-positive group),
whereas the remaining seven showed no detectable uptake (BAT-negative group). The
BMI and body fat content were similar in the two groups. Under warm conditions at
27 °C, the energy expenditure of the BAT-positive group estimated by indirect
calorimetry was 1,446 ± 97 kcal/day, being comparable with that of the
BAT-negative group (1,434 ± 246 kcal/day). After cold exposure, the energy
expenditure increased markedly by 410
± 293 (P < 0.05) and slightly by 42 ±
114 kcal/day (P = 0.37) in the BAT-positive and -negative groups, respectively. A
positive correlation (P < 0.05) was found between the cold-induced rise in energy
expenditure and the BAT activity quantified from FDG uptake. After cold exposure,
the skin temperature in the supraclavicular region close to BAT deposits dropped
by 0.14 °C in the BAT-positive group, whereas it dropped more markedly (P < 0.01)
by 0.60 °C in the BAT-negative group. The skin temperature drop in other regions
apart from BAT deposits was similar in the two groups. These results suggest that
BAT is involved in cold-induced increases in whole-body energy expenditure, and,
thereby, the control of body temperature and adiposity in adult humans.

PMID: 20448535

Check out that massive increase in calorie burning from just 2 hours of mild cold exposure (19C or 66F) plus icing the legs intermittently!

 

-Gordo

 


Edited by Gordo, 13 June 2016 - 08:25 PM.

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#9 deanp

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Posted 13 June 2016 - 11:20 PM

All,

 

It looks like CE is getting more attention. Just today I received a heads up about a new interview with Wim Hof (aka the Iceman) by one of my favorite podcasters, Rich Roll. It has the provocative subtitle "Cold is God", so it has got to be good ☺. The topics Rich covers with Wim include not just cold exposure, but many of the other extreme practices and endeavors Wim has accomplished, including (as summarized by Rich) the following topics (I've highlighted the CE-related topics in bold):

  • how to awaken inner dormant ability
  • how to control metabolic pathways
  • the science behind the Wim Hof Method [cold exposure and special breathing technique]
  • surviving grief — catalyst for change & exploration
  • delving deeper into consciousness
  • furthering the message with 26 world records
  • being of service and in tune with nature
  • voluntary activation of the sympathetic nervous system
  • breathing & extreme cold
  • pH levels: acidosis vs. alkalosis
  • voluntary E. coli endotoxin injection
  • Mount Kilimanjaro ascent
  • pain management & inflammation studies
  • reversing chronic conditions
  • combatting depression, grief & addiction
  • intermittent hypoxic training
  • spiritual, environmental, ethical, and health crises
  • the primal path
  • typical day with Wim Hof

I haven't listened to this interview yet (I plan to tomorrow). But having watched Wim's TEDx Talk (embedded below), I'm really looking forward to hearing more details about his approach to cold exposure, as well as other ways of challenging himself and pushing the envelope of human potential.

 

--Dean

 

 


Edited by deanp, 13 June 2016 - 11:47 PM.

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#10 deanp

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Posted 13 June 2016 - 11:38 PM

Drew,

 

Yes, you can eat ice chips or drink cold water to experiment with CE. Cold showers work as well. But I prefer a cooling vest, which has the side benefit of serving as an inexpensive air-condition replacement now that summer has arrived!

 

You can purchase the TechKewl vest ($123-159 on Amazon) that Gordo is wearing in the picture above, or you can opt for the Cool Fat Burner vest ($70-$158 direct from CoolFatBurner.com) that I prefer (see my full review here), or you can build your own inexpensive cooling vest with a DIY solution described here by Todd S.

 

Which ever way to prefer, it's easy and (potentially) inexpensive to start experimenting with CE for yourself.

 

--Dean

 


Edited by deanp, 13 June 2016 - 11:39 PM.

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#11 drew_ab

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Posted 15 June 2016 - 12:15 PM

Have any of you come across anything that suggests heat exposure (ie. warm house, sauna, etc.) will negate the effects of cold exposure?  How about the effects of cold exposure on hormones like T, E, DHT, etc.?  Anecdotally, what (if any) effects have you noticed in yourselves?

 

Thanks for answering my other questions so far.



#12 deanp

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Posted 15 June 2016 - 03:17 PM

Drew,

 

Good questions. Regarding heat vs. cold exposure. Exposure to both temperature extremes upregulate many of the same so-called "heat shock proteins". Below is the section from my Cold Exposure Albatross mega-post1 to the CR Society Forum thread on cold exposure in which I delve into the details of  science supporting the benefits of cold exposure (which ironically started out as a simple response to Michael's skepticism). The interesting thing is that not only does cold exposure upregulate many of the same HSPs as heat exposure (e.g. saunas), it also potentiates the release of HSPs in response to extreme heat stress. I.e. cold exposure protects the body at both temperature extremes. So in short, it appears to me that both heat and cold exposure are complementary in some respects.

 

Regarding the influence of CE on the hormones you listed, here is a post about what I've come across regarding testosterone (and IGF-1). Basically, cold exposure in humans has been found to reduce exercise-induced inflammation and the elevation in testosterone & IGF-1 that accompanies exercise. For folks interested in getting 'uge, that may be considered a bad thing, but for those of us interested in longevity, perhaps the opposite is the case, given CR's well known effects on those two hormones...

 

Begin excerpt from here on heat shock proteins and cold exposure:

 

For those not familiar with Heat Shock Proteins (HSPs) they are a family of proteins the body produces in response to various stressful conditions, not just thermal extremes. Their primary role appears to be to act as a chaperone to prevent misfolding and aggregation of other proteins under stressful conditions. They also appear to serve as signalling molecules for cellular stress, that kick in a host of other  biochemical responses, including beneficial chances to the cardiovascular and immune systems. Both acute and chronic cold exposure trigger the induction of a variety of HSPs as a result of elevated norepinephrine [1].

 

Here is the section from the Cold Exposure Albatross post discussing heat shock proteins (follow link for references):

 

Improved Heat Tolerance / Increased Heat Shock Protein Expression - While it's not clear heat shock proteins (HSPs) increase lifespan in mammals like they do in lower organisms (like C elegans), HSPs are definitely important for stress resistance [18], and in particularly for the ability to cope with heat stress, hence the name. CR preserves HSP induction in response to thermal stress in aging mice [20], and prevent the age-related decline in several heat shock protein [21], and especially HSP70 [19] and HSP90 [21].  So might the cold of CE reduce one's heat shock protein levels, and ruin one's ability to cope with high temperatures? Nope. Quite the opposite in fact. 
 
Study [13] found that the induction of three important heat shock proteins, Hsp70, Hsp90 and Hsp110 was higher in tissues of mice housed at 22 °C than mice housed at thermoneutrality (30°C) following 6 h of heat stress (i.e. high temperatures) which elevated core body temperature to 39.5 °C. So it looks like relative to living at comfortable, thermoneutral temperatures, CE helps with thermal tolerance at both extremes - hot and cold, by improving heat shock protein induction. Interestingly, [14] found increased expression of one of Hsp70 is associated with improved insulin sensitivity in monkeys and humans - "higher levels of [...] HSP70 protect against insulin resistance development during healthy aging." Review article [16] is a good discussion of heat shock proteins and lifespan in general, and [17] is a study that shows genetic mutations in heat shock proteins may be associated with improved human survival.
 
Here is a recent study [2] that  I overlooked in the Albatross post, which found people stationed in Antarctica over the winter and subject to cold had higher circulating HSP65 (the only HSP they tested for) than a control group stationed in tropical India over the same period.
 
In summary, both acute and chronic cold exposure upregulates HSPs in all organisms tested, from flies to rodents to humans. Yet one more benefit of cold. As to your question about the potential benefits (or harm) of rapid thermal cycling (e.g. a plunge into cold water after a sauna), I haven't come across evidence pointing one way or the other. But Rhonda Patrick has a pretty good report and YouTube video on the many benefits of saunas.
 
--Dean
 
1Albatross being an obscure allusion to Michael Rae's mega-post to the CR Society email list many years ago detailing his DHA-Accelerated Aging Hypothesis - which he said was like an "albatross around his neck" he labored on it for so long. Some of his albatross post is available here and more recent evidence discussed here. Michael, do you have a link to the original, full version?
 
------------
[1] Am J Physiol. 1995 Jul;269(1 Pt 2):R38-47.
 
Characterization and regulation of cold-induced heat shock protein expression in 
mouse brown adipose tissue.
 
Matz JM(1), Blake MJ, Tatelman HM, Lavoi KP, Holbrook NJ.
 
Author information: 
(1)Department of Pharmacology and Toxicology, University of North Dakota, Grand
Forks 58202, USA.
 
The accumulation of heat shock proteins (HSPs) after the exposure of cells or
organisms to elevated temperatures is well established. It is also known that a
variety of other environmental and cellular metabolic stressors can induce HSP
synthesis. However, few studies have investigated the effect of cold temperature 
on HSP expression. Here we report that exposure of Institute of Cancer Research
(ICR) mice to cold ambient temperatures results in a tissue-selective induction
of HSPs in brown adipose tissue (BAT) coincident with the induction of
mitochondrial uncoupling protein synthesis. Cold-induced HSP expression is
associated with enhanced binding of heat shock transcription factors to DNA,
similar to that which occurs after exposure of cells or tissues to heat and other
metabolic stresses. Adrenergic receptor antagonists were found to block
cold-induced HSP70 expression in BAT, whereas adrenergic agonists induced BAT HSP
expression in the absence of cold exposure. These findings suggest that
norepinephrine, released in response to cold exposure, induces HSP expression in 
BAT. Norepinephrine appears to initiate transcription of HSP genes after binding 
to BAT adrenergic receptors through, as yet, undetermined signal transduction
pathways. Thermogenesis results from an increase in activity and synthesis of
several metabolic enzymes in BAT of animals exposed to cold challenge. The
concomitant increase in HSPs may function to facilitate the translocation and
activity of the enzymes involved in this process.
 
PMID: 7631901
 
-------------
[2] International Journal of Scientific and Research Publications, Volume 4, Issue 5, May 2014 1
ISSN 2250-3153
 
Heat Shock Protein Response to Chronic Cold Exposure in Antarctic Expedition Members
 
IB Udaya*
, CC Laxmi**
, AK Kavitha†
, TN Satyaprabha††
, TR Raju#
, Shripad Patil ##
 
 
 Abstract- The heat shock response is seen when cells are
exposed to extremes of thermal environment, which may be
acute or chronic. The heat shock response is featured by
increased expression of heat shock proteins (HSPs). One such
key stresses is extreme cold environment as seen in Antarctica.
The Antarctic continent on the planet Earth is full of
environmental challenges. It is considered as natural stress
model. The objective of this study was to study the effect of
chronic cold environment on HSP levels. Seventeen healthy men
of XXVI Indian Antarctic expedition with mean age of
39.7±1.95 years and age ranged from 29 to 56 years participated
in this study. Antibodies of IgG, IgA and IgM classes against
HSP65 were investigated by indirect ELISA method. Samples
were collected in 2 phases. In phase-1, pre-expedition samples
were collected before leaving to Antarctica at National Center for
Antarctic and ocean research (NCAOR), Goa. In phase-2, end
expedition samples were collected after 11 months of stay in
Antarctica in an Indian permanent station (Maitri) during polar
days. The raw data on analysis using statistical tool revealed that
the anti-HSP65 IgM antibody were significantly elevated (p=
<0.001). It was observed that the anti-HSP65 antibodies were
increased in expedition members compared with the control
group who stayed in India. The present study concluded that HSP
expression increased in Indian Antarctic expedition members
who were exposed to chronic cold stress in Antarctica.
 
 Index Terms- HSP65, Chronic cold stress, Antarctica, Immunological response.
 
---------
[13] Int J Hyperthermia. 2014 Dec;30(8):540-6. doi: 10.3109/02656736.2014.981300.
 
Housing temperature influences the pattern of heat shock protein induction in
mice following mild whole body hyperthermia.
 
Eng JW(1), Reed CB, Kokolus KM, Repasky EA.
 
Author information: 
(1)Department of Immunology, Roswell Park Cancer Institute , Buffalo, New York , 
USA.
 
PURPOSE: Researchers studying the murine response to stress generally use mice
housed under standard, nationally mandated conditions as controls. Few
investigators are concerned whether basic physical aspects of mouse housing could
be an additional source of stress, capable of influencing the subsequent impact
of an experimentally applied stressor. We have recently become aware of the
potential for housing conditions to impact important physiological and
immunological properties in mice.
MATERIALS AND METHODS: Here we sought to determine whether housing mice at
standard temperature (ST; 22 °C) vs. thermoneutral temperature (TT; 30 °C)
influences baseline expression of heat shock proteins (HSPs) and their typical
induction following a whole body heating.
RESULTS: There were no significant differences in baseline expression of HSPs at 
ST and TT. However, in several cases, the induction of Hsp70, Hsp110 and Hsp90 in
tissues of mice maintained at ST was greater than at TT following 6 h of heating 
(which elevated core body temperature to 39.5 °C). This loss of HSP induction was
also seen when mice housed at ST were treated with propranolol, a β-adrenergic
receptor antagonist, used clinically to treat hypertension and stress.
CONCLUSIONS: Taken together, these data show that housing temperature
significantly influences the expression of HSPs in mice after whole body heating 
and thus should be considered when stress responses are studied in mice.
 
PMCID: PMC4340593
PMID: 25430986
 
-----------
[14] J Gerontol A Biol Sci Med Sci. 2015 Feb;70(2):155-62. doi: 10.1093/gerona/glu015.
Epub 2014 Feb 14.
 
Muscle heat shock protein 70 predicts insulin resistance with aging.
 
Chichester L(1), Wylie AT(1), Craft S(2), Kavanagh K(3).
 
Author information: 
(1)Departments of Pathology and. (2)Internal Medicine, Wake Forest School of
Medicine, Winston-Salem, North Carolina. (3)Departments of Pathology and
kkavanag@wakehealth.edu.
 
Heat shock protein 70 (HSP70) protects cells from accumulating damaged proteins
and age-related functional decline. We studied plasma and skeletal muscle (SkM)
HSP70 levels in adult vervet monkeys (life span ≈ 25 years) at baseline and after
4 years (≈10 human years). Insulin, glucose, homeostasis model assessment scores,
triglycerides, high-density lipoprotein and total plasma cholesterol, body
weight, body mass index, and waist circumference were measured repeatedly, with
change over time estimated by individual regression slopes. Low baseline SkM
HSP70 was a proximal marker for developing insulin resistance and was seen in
monkeys whose insulin and homeostasis model assessment increased more rapidly
over time. Changes in SkM HSP70 inversely correlated with insulin and homeostasis
model assessment trajectories such that a positive change in SkM level was
beneficial. The strength of the relationship between changes in SkM HSP70 and
insulin remained unchanged after adjustment for all covariates. Younger monkeys
drove these relationships, with HSP70 alone being predictive of insulin changes
with aging. Plasma and SkM HSP70 were unrelated and HSP70 release from peripheral
blood mononuclear cells was positively associated with insulin concentrations in 
contrast to SkM. Results from aged humans confirmed this positive association of 
plasma HSP70 and insulin. In conclusion, higher levels of SkM HSP70 protect
against insulin resistance development during healthy aging.
 
© The Author 2014. Published by Oxford University Press on behalf of The
Gerontological Society of America. All rights reserved. For permissions, please
e-mail: journals.permissions@oup.com.
 
PMCID: PMC4311181
PMID: 24532784
 
-------------
[15] Ageing Res Rev. 2011 Jan;10(1):153-62. doi: 10.1016/j.arr.2010.10.001. Epub 2010 
Oct 20.
 
Caloric restriction and longevity: effects of reduced body temperature.
 
Carrillo AE(1), Flouris AD.
 
Author information: 
(1)FAME Laboratory, Institute of Human Performance and Rehabilitation, Centre for
Research and Technology Thessaly, Trikala, Greece.
 
Caloric restriction (CR) causes a reduction in body temperature (T(b)) which is
suggested to contribute to changes that increase lifespan. Moreover, low T(b) has
been shown to improve health and longevity independent of CR. In this review we
examine the connections between CR, T(b) and mechanisms that influence longevity 
and ageing. Recent findings regarding the overlapping mechanisms of CR and T(b)
that benefit longevity are discussed, including changes in body composition,
hormone regulation, and gene expression, as well as reductions in low-level
inflammation and reactive oxygen species-induced molecular damage. This
information is summarized in a model describing how CR and low T(b), both
synergistically and independently, increase lifespan. Moreover, the nascent
notion that the rate of ageing may be pre-programmed in response to environmental
influences at critical periods of early development is also considered. Based on 
current evidence, it is concluded that low T(b) plays an integral role in
mediating the effects of CR on health and longevity, and that low T(b) may exert 
independent biological changes that increase lifespan. Our understanding of the
overlap between CR- and T(b)-mediated longevity remains incomplete and should be 
explored in future research.
 
Copyright © 2010 Elsevier B.V. All rights reserved.
 
PMID: 20969980
 
-------------
[16] Nat Rev Mol Cell Biol. 2010 Aug;11(8):545-55. doi: 10.1038/nrm2938. Epub 2010 Jul
14.
 
Heat shock factors: integrators of cell stress, development and lifespan.
 
Akerfelt M(1), Morimoto RI, Sistonen L.
 
Author information: 
(1)Department of Biosciences, Abo Akademi University, BioCity, 20520 Turku,
Finland.
 
Heat shock factors (HSFs) are essential for all organisms to survive exposures to
acute stress. They are best known as inducible transcriptional regulators of
genes encoding molecular chaperones and other stress proteins. Four members of
the HSF family are also important for normal development and lifespan-enhancing
pathways, and the repertoire of HSF targets has thus expanded well beyond the
heat shock genes. These unexpected observations have uncovered complex layers of 
post-translational regulation of HSFs that integrate the metabolic state of the
cell with stress biology, and in doing so control fundamental aspects of the
health of the proteome and ageing.
 
PMCID: PMC3402356
PMID: 20628411

 

-----------

[17] Age (Dordr). 2013 Aug;35(4):1367-76. doi: 10.1007/s11357-012-9417-7. Epub 2012

May 4.
 
Association of heat shock proteins with all-cause mortality.
 
Broer L(1), Demerath EW, Garcia ME, Homuth G, Kaplan RC, Lunetta KL, Tanaka T,
Tranah GJ, Walter S, Arnold AM, Atzmon G, Harris TB, Hoffmann W, Karasik D, Kiel 
DP, Kocher T, Launer LJ, Lohman KK, Rotter JI, Tiemeier H, Uitterlinden AG,
Wallaschofski H, Bandinelli S, Dörr M, Ferrucci L, Franceschini N, Gudnason V,
Hofman A, Liu Y, Murabito JM, Newman AB, Oostra BA, Psaty BM, Smith AV, van Duijn
CM.
 
Author information: 
(1)Department of Epidemiology, Erasmus Medical Center, Dr. Molewaterplein 50,
PO-Box 2040, 3000, CA, Rotterdam, The Netherlands.
 
Experimental mild heat shock is widely known as an intervention that results in
extended longevity in various models along the evolutionary lineage. Heat shock
proteins (HSPs) are highly upregulated immediately after a heat shock. The
elevation in HSP levels was shown to inhibit stress-mediated cell death, and
recent experiments indicate a highly versatile role for these proteins as
inhibitors of programmed cell death. In this study, we examined common genetic
variations in 31 genes encoding all members of the HSP70, small HSP, and heat
shock factor (HSF) families for their association with all-cause mortality. Our
discovery cohort was the Rotterdam study (RS1) containing 5,974 participants aged
55 years and older (3,174 deaths). We assessed 4,430 single nucleotide
polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina.
After adjusting for multiple testing by permutation analysis, three SNPs showed
evidence for association with all-cause mortality in RS1. These findings were
followed in eight independent population-based cohorts, leading to a total of
25,007 participants (8,444 deaths). In the replication phase, only HSF2
(rs1416733) remained significantly associated with all-cause mortality. Rs1416733
is a known cis-eQTL for HSF2. Our findings suggest a role of HSF2 in all-cause
mortality.
 
PMCID: PMC3705092
PMID: 22555621
 
---------
[18] Sørensen, J. G., Kristensen, T. N. and Loeschcke, V. (2003), The evolutionary and ecological role of heat shock proteins. Ecology Letters, 6: 1025–1037. doi:10.1046/j.1461-0248.2003.00528.x
 
------------
[19] Dev Genet. 1996;18(2):114-24.
 
Effect of caloric restriction on the expression of heat shock protein 70 and the 
activation of heat shock transcription factor 1.
 
Heydari AR(1), You S, Takahashi R, Gutsmann A, Sarge KD, Richardson A.
 
Author information: 
(1)Geriatric Research, Education and Clinical Center, Audie L. Murphy Memorial
Veterans Hospital, San Antonio, TX 78284, USA.
 
The regulation of heat shock protein 70 (hsp70) expression is an excellent
example of a cellular mechanism that has evolved to protect all living organisms 
from various types of physiological stresses; therefore, the reported age-related
alterations in the ability of cells to express hsp70 in response to stress could 
seriously compromise the ability of a senescent organism in respond to changes in
its environment. Because caloric restriction (CR) is the only experimental
manipulation known to retard aging and increase the survival of rodents, it was
of interest to analyze the effect of CR on the age-related alteration in the
induction of hsp70 expression in rat hepatocytes. The effect of CR on the nuclear
transcription of hsp70 gene in rat hepatocytes in response to various levels of
heat shock was determined, and it was found that the age-related decline in the
transcription of hsp70 at all temperatures studied was reversed by CR. Because
the heat shock transcription factor (HSF) mediates the heat-induced transcription
of hsp70, the effect of CR on the induction of HSF binding activity by heat shock
was studied and found to arise from HSF1, which has been shown to be involved in 
the induction of HSF binding activity in other cell types. The age-related
decrease in the induction of HSF1 binding activity in rat hepatocytes was
reversed by CR, and did not appear to be due to an accumulation of inhibitory
molecules with age. Interestingly, the level of HSF1 protein was significantly
higher in hepatocytes isolated from old rats fed ad libitum compared to
hepatocytes obtained from rats fed the CR diet even though the levels of HSF1
binding activity were lower for hepatocytes isolated from the old rats fed ad
libitum. The levels of the mRNA transcript for HSF1 was not significantly altered
by age or CR. Thus, the changes in HSF1 binding activity with age and CR do not
arise from changes in the level of HSF1 protein available for activation.
 
PMID: 8934873

 


Edited by deanp, 15 June 2016 - 03:23 PM.

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#13 Gordo

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Posted 23 July 2016 - 02:56 PM

For anyone who has read this thread and thought about buying a cooling vest but balked at the cost, Dean recently described his homemade cooling vest below, I think it's a great deal and have already ordered these cheap cooling packs from Amazon to make a couple extra cooling vests myself.  Below is copied from Dean (not written by me):

__________________________________________________________________________________________

Cool Fat Burner Knock-off - A $13 DIY Cooling Vest (Including Backup Ice Packs)

 

As anyone reading this will know by now, I'm a big fan Cool Fat Burner (CFB) cooling vest(s). But now that it's summertime and hot here in Pittsburgh, and I'm going through all my CFB cool packs (12 of them) during the course of the day. Additional cold packs from CFB are not cheap - $50 for a pack of four.

 

So I went looking online for alternatives, and boy did find a deal. Amazon sells these cold packs that are virtually identical to the "hardcore packs" sold by CFB. They are 6x10" and 24oz vs. the CFB packs which are 6x9" and 22oz. The extra 1" length is no problem, since the CFB pockets have plenty of extra room in that direction.

 

And you can't beat the price - they are $13 for a set of 9 ($1.46 ea), vs. $50 + $10 tax & shipping for a set of 4 from CFB ($15 ea). That is less than 1/10th the price! So that's part one of a really inexpensive DIY cooling vest...

 

Now the question is how to drape them to you body, without shelling out for the CFB vest, which cost $70 + shipping?

 

Ever the engineer, here is a free cooling vest solution I came up with, made from an old long-sleeve shirt and some safety pins. Here is a picture of the pinned shirt, to create four pockets for the ice packs, just like the "classic" CFB vest has:

 

fhSRwmq.png

 

You simply slip four frozen ice packs into the pockets through the shirt's neck hole, like this:

 

thAlEX9.png

 

 

Then put it on over you head putting your head through the hole created by the pinned sleeves, in order to wear the shirt over you shoulders like a cape. Here is what it looks like on:

 

CH6s1Eo.png  JM49OIK.png

 

For anyone who wants to get fancy, you could sew along the lines of safety pins, and cut off the excess shirt material. But this way, I don't even ruin the shirt, in case the Steelers make it to the playoffs again this year (Go Steelers!). ☺

 

In short, with this DIY cooling vest and the Amazon ice packs (9x) above, you too can experiment with cold exposure for only $13. The equivalent from Cool Fat Burner would be $70 for the vest and four ice packs, plus another $50 for a second set of ice packs, or a total of $120. With tax and shipping the CFB equivalent comes to $141. So at $13, this DIY cooling vest solution is more than 90% off - Can't beat that!

 

Let me know what you think, and if anyone else tries it.

 

Happy chilling!

 

--Dean

 

P.S. For anyone wondering how I manage all those ice packs in my freezer, here is a rack I created for them out of some old corner freezer shelving to allow air circulation around the packs, and for easy transfer in/out of the freezer:

 

bcrhFnS.png

 

fFzwBxT.png

 

UQ45IgH.png

 

E21GWa2.png

 

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#14 Gordo

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Posted 24 July 2016 - 01:07 PM

Hat tip to Michael Rae for this one...

In a first of its kind announcement, a small biotech company:

BioRestorative Therapies: A Stem Cell Biotechnology Company

Has revealed that we are one step closer to doing human brown fat transplants (from stem cell derived, engineered brown fat tissue).  This is an exciting development, I can picture a future where many people get "amped up" brown fat not only to "fix" metabolic disorders and diabetes, but to optimize their health, weight, and longevity.  This could also potentially open doors to many people with limited, non-existent, or impaired brown fat (in studies these are referred to as BAT-).

 

MELVILLE, N.Y., May 23, 2016 (GLOBE NEWSWIRE) – BioRestorative Therapies, Inc. ("BRT" or "the Company") (BRTX), a life sciences company focused on stem cell-based therapies, today announced that promising data has been developed on the transplantation of human stem cell-derived tissue engineered brown fat into an encapsulation device to be used as a cell delivery system for the Company’s metabolic platform program for the treatment of type 2 diabetes, obesity, hyperlipidemia and hypertension. This advancement may lead to successful transplantation of brown fat in humans.

 

The Company’s study entitled, “In Vitro Evaluation of an Encapsulation System for the Transplantation of a Human Stem Cell-Derived Tissue Engineered Brown Fat” has been accepted for presentation at the upcoming International Society for Cellular Therapy (ISCT) Annual Meeting (Singapore, May 25 – 28, 2016). The study showed how brown adipose-derived stem cells, that were differentiated step-wise to functional 3D brown adipocyte constructs, were loaded into an encapsulation device designed to be used as a cell-based therapeutic for treating metabolic disorders. These cells appear to display high viability and they differentiated into metabolically active brown adipocytes as shown by UCP-1 expression.

 

By successfully seeding human brown adipose derived stem cells into an encapsulation device, the Company is advancing the development of its cell therapy program to treat metabolic disorders. The Company’s study is expected to progress its program to enable transplanted brown adipose cells to effectively maintain or regulate normal metabolism in humans. BRT is evaluating the next generation of brown adipose tissue constructs that will first be tested in small animal models. No assurance can be given that this delivery system will be effective in vivo in animals or humans.

 

“We are encouraged with these results and look forward to continuing our efforts in achieving our goals to develop novel cell-based therapies for the treatment of metabolic disorders," said Mark Weinreb, CEO.

 

About BioRestorative Therapies, Inc.

BioRestorative Therapies, Inc. (www.biorestorative.com) develops therapeutic products using cell and tissue protocols, primarily involving adult stem cells. Our two core programs, as described below, relate to the treatment of disc/spine disease and metabolic disorders:

 

• Disc/Spine Program (brtxDISCTM): Our lead cell therapy candidate, BRTX-100, is a product formulated from autologous (or a person’s own) cultured mesenchymal stem cells collected from the patient’s bone marrow. We intend that the product will be used for the non-surgical treatment of protruding and bulging lumbar discs in patients suffering from chronic lumbar disc disease. The BRTX-100 production process involves collecting a patient’s bone marrow, isolating and culturing stem cells from the bone marrow and cryopreserving the cells. BRTX-100 is then injected by a physician into the patient’s damaged disc in an outpatient procedure. The treatment is intended for patients whose pain has not been alleviated by non-invasive procedures and who potentially face the prospect of surgery.

 

• Metabolic Program (ThermoStem®): We are developing a cell-based therapy to target obesity and metabolic disorders using brown adipose (fat) derived stem cells to generate brown adipose tissue (“BAT”). BAT is intended to mimic naturally occurring brown adipose depots that regulate metabolic homeostasis in humans. Initial preclinical research indicates that increased amounts of brown fat in the body may be responsible for additional caloric burning as well as reduced glucose and lipid levels. Researchers have found that people with higher levels of brown fat may have a reduced risk for obesity and diabetes.

 

Forward-Looking Statements

 

This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events or results to differ materially from those projected in the forward-looking statements as a result of various factors and other risks, including those set forth in the Company's Form 10-K filed with the Securities and Exchange Commission. You should consider these factors in evaluating the forward- looking statements included herein, and not place undue reliance on such statements. The forward- looking statements in this release are made as of the date hereof and the Company undertakes no obligation to update such statements.


Edited by Gordo, 24 July 2016 - 01:09 PM.


#15 MidwestGreg

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Posted 24 July 2016 - 05:00 PM

Interesting Gordo.

 

Do you think that one would get similar benefits from using a cooling glove?

 

Stanford article here: http://news.stanford...esearch-082912/

 

"The rapid thermal exchange device, nicknamed ‘the glove,’ creates a vacuum to draw blood to the surface of the palms. Cold circulating water cools the blood, which returns to the heart and rapidly lowers the body’s core temperature.

“Equal to or substantially better than steroids … and it’s not illegal.”

This is the sort of claim you see in spam email subject lines, not in discussions of mammalian thermoregulation. Even the man making the statement, Stanford biology researcher Dennis Grahn, seems bemused. “We really stumbled on this by accident,” he said. “We wanted to get a model for studying heat dissipation.”

 

But for more than a decade now, Grahn and biology Professor H. Craig Heller have been pursuing a serendipitous find: by taking advantage of specialized heat-transfer veins in the palms of hands, they can rapidly cool athletes’ core temperatures – and dramatically improve exercise recovery and performance."

 

Commercial version here for sale (very expensive - no affiliation): http://www.avacore.com/

 

DIY version here: http://www.instructa...oreControl-DIY/

 

I have been looking at the DIY version to see if I could use one of these devices to periodically cool myself down on hot days while motorcycle riding.



#16 Gordo

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Posted 24 July 2016 - 07:25 PM

Hey Greg, thanks for posting that DIY link!  Its funny because I had been planning to build a vacuum cooler, good to see others have already done this and posted plans.  I have also found this "next gen" DIY version.  That said, the more I read and think about it, the more skeptical I've become, in fact I'm so skeptical now that I don't even plan to build one.  The early devices got a lot of positive press and hype, but the science doesn't seem all that impressive to me.  I think there has been a lot of psychosomatic based exaggeration around the effectiveness of this cooling method (below you can even see ESPN jumping on the bandwagon).  

 

I know the promoters say the vacuum is necessary to prevent capillary constriction, but who has done an actual A/B comparison vs. just dunking your arm in a big tube/bucket full of ice water?  Give me a well controlled study.  I can put together a nice long PVC tube with a water tight cap on the end for a couple of dollars, fill it with crushed ice and water, and plunge my entire hot sweaty arm into it, I STRONGLY suspect I'll get better cooling that way!  Make 2 of them, plunge both arms in, and I bet you'd get shockingly more effective rapid cooling.  I think it would be hilarious to see an entire football team's bench full of players with both arms submerged in ice water.

 

 

 

 

628x471.jpg

corecontrol.jpg

play_e_corecontrol01jr_576.jpg

 

ESPN's REVIEW of the above "coreControl" ($895)


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#17 Gordo

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Posted 31 July 2016 - 03:16 AM

I found this study on hand based cooling techniques, perhaps I was too hasty in dismissing the idea, it does seem to cool the core pretty well, and indeed the vacuum component was found to be critically important.  That said, based on some additional searching, I believe whole body cold water immersion is twice as effective at rapidly cooling core temperature, and just eating/drinking crushed ice is likely to be just as effective, but I may yet build a hand vac cooler.

 

In other news, there has been a recent deluge of new hits for "brown adipose" on google scholar.  The ones of interest to me include:

 

1) An additional drug/herb has been identified as a BAT activator, called Bofutsushosan.

 

2) These scientists are using a DNA Virus to boost BAT activity in mice.

 

3) Not really news to us, but a new study finds that a metformin-induced increase of lipid and glucose utilization in BAT may participate in the mechanism of improving metabolic syndrome and related disorders.

 

4) Possibly the most interesting of the bunch to me, a new patent application has been filed called Methods and Devices for Activating Brown Adipose Tissue Using Electrical Energy  "Methods and devices are provided for activating brown adipose tissue (BAT) using electrical energy. In general, the methods and devices can facilitate activation of BAT to increase thermogenesis. The BAT can be activated by applying an electrical signal thereto that can be configured to target sympathetic nerves that can directly innervate the BAT. The electrical signal can be configured to target the sympathetic nerves using fiber diameter selectivity. In other words, the electrical signal can be configured to activate nerve fibers having a first diameter without activating nerve fibers having diameters different than the first diameter. Sympathetic nerves include postganglionic unmyelinated, small diameter fibers, while parasympathetic nerves that can directly innervate BAT include preganglionic myelinated, larger diameter fibers. The electrical signal can be configured to target and activate the postganglionic unmyelinated, small diameter fibers without activating the preganglionic myelinated, larger diameter fibers."

 

5) Two hits related to new ways of imaging BAT:  Certain curcumin analogs can be used to non-invasively image BAT in vivo (patent application).   AND  Measuring Supraclavicular Skin Temperature for the Detection of Brown Adipose Tissue in Adult Humans using Infrared Thermography

 

6) New study looks at the role of leptin on BAT:  The physiological effect of leptin to reduce thermal conductance contributes to maintenance of core body temperature under sub-thermoneutral conditions.

 

7) New study looks at diet induced thermogenesis (DIT) in particular, and how it relates to BAT.  No surprise, but DIT and fat utilization were higher in BAT-positive subjects compared to BAT-negative subjects, suggesting that BAT has a physiologic role in energy metabolism.

 

8) I think we've only touched the surface on this topic, and we should discuss it more.  Some of the early CE pioneers talk about hot to cold transittions but thus far I dont' remember seeing much data about this.  A new study seems to provide evidence of increased BAT activity when going from hot to cold vs. room temp to cold.  This could potentially change the way some of us practice CE.  I would love to see more research along these lines.  "Conclusion: Acclimation at 32ºC produces a greater and earlier response to cold in the supraclavicular area than room temperature acclimation. The thermal response after 32ºC acclimation is reproducible and unlikely to be affected by outdoor temperature and subcutaneous fat in the neck. These data suggest that the use of infrared thermography using the 32ºC-cold protocol may be effective for detecting the metabolic activity of brown adipose tissue."  Also note that these guys induced BAT activity using only mild cooling of the torso with cooling blankets.

 
9) Fiber Boosts BAT and WAT Browning  "Taken together, our results suggested that cereal dietary fiber enhanced adipocyte lipolysis by the cAMP-PKA-HSL pathway and promoted WAT browning by activation of UCP1, and consequently reduced visceral fat mass in response to HFD feeding."
 
10) Cold exposure has a beneficial effect on the gut microbiome!  Note:  I believe there is a related link here between CE and better sleep, related to melatonin production in the GI tract, but at this time that is speculative.  All I know is is that CE seems to have a very beneficial impact on sleep and I await further studies to document this.
 
11) Time restricted feeding (tRF) boosts BAT activity. This is a new paper by Longo, well know in the longevity science circles.  I practice tRF, only eating between the hours of noon and 7PM. tRF has numerous documented health benefits and is something I highly recommend.
 
12) I'm including this one only as a joke.  Apparently nitrous oxide should NOT be added to the list of BAT activators.  That's a real shame because further experimentation could have been fun!  rolleyes.gif
 
Regards,
Gordo
 

 


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#18 Gordo

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Posted 06 August 2016 - 04:54 AM

More on cold microbiota:

 

Brown fat induction in treatment of metabolic disorders

"Our recent findings show that cold exposure leads to marked shift of the microbiota composition, referred to as cold microbiota (Chevalier et al., 2015). Transplantation of the cold microbiota to germ-free mice is sufficient to increase insulin sensitivity of the host, and enable tolerance to cold partly by promoting the white fat browning, leading to increased energy expenditure and fat loss. During prolonged cold however, the body weight loss is atPL 7 26 Maced. pharm. bull., 62 (suppl) 25 - 26 (2016) Mirko Trajkovski tenuated, caused by adaptive mechanisms maximizing caloric uptake and increasing intestinal, villi and microvilli lengths. This increased absorptive surface is transferable with the cold microbiota leading to altered intestinal gene expression promoting tissue remodelling and suppression of apoptosis - effect diminished by co-transplanting the most cold-downregulatedbacterial strain Akkermansiamuciniphila during the cold microbiota transfer. Our results demonstrate the microbiota as a key factor orchestrating the overall energy homeostasis during increased demand ((Chevalier et al., 2015). We recently also showed that the development of functional beige fat is promoted by microbiota depletion either by means of antibiotic treatment or in germ-free mice within the white adipose tissues (SuárezZamorano et al., 2015). This leads to improved glucose tolerance, insulin sensitivity and decreased white fat and adipocyte size in lean mice and obese mice."


From the renowned Dr. John Speakman:  

Type 2 diabetes, but not obesity, prevalence is positively associated with ambient temperature

 

Nothing really earth shattering, but more people are starting to understand that cold exposure helps prevent diabetes even if it makes you hungry ;)

 

"Previous work has demonstrated that this BAT activity is responsive to changes in ambient temperature11,12,13,14,15,16 and that levels of BAT activity vary seasonally17,18, being higher in the winter when it is colder. This indirect evidence suggests that humans do indeed expend energy on thermoregulation, and more so when it is colder. This effect occurs despite spending long periods of time indoors buffered from such ambient extremes by the spread of central heating and air-conditioning19,20."

 

srep30409-f3.jpg

 


#19 Gordo

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Posted 17 August 2016 - 05:57 PM

Respectfully ripped from Dean P:

 

There is a new paper out [1] (popular account) that seems to me to do a pretty good job summarizing what we know about the different causes of aging. They have the same perspective as Aubrey, Michael & SENS - namely that at its root aging is a result of metabolic damage accumulation. But they appear to have a slightly different taxonomy than Aubrey's "7 deadly causes", although I'll leave it to Michael to map between the two. Here is there graphic showing the "Hallmarks of Aging":

 

2Vwpk9S.png

 

One thing that jumped out at me (and that I've highlighted above in yellow) was the role peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC1α) appears to play in the various hallmarks of aging. In fact, a drop in PGC1α signalling is implicated in four of the nine hallmarks of aging. This interests me, because PGC1α promotes mitochondria biogenesis, and is upregulated by cold exposure [2], as we've seen many times on the cold exposure thread.

 

Sadly, the authors don't mention cold exposure as a potential means to ameliorate the aging process. Instead they focus on CR, amino-acid restriction, CR-mimetics, time-restricted feeding, and exercise as the most promising longevity interventions. Oh well, someday the benefits of cold exposure will be more widely recognized.

 

Overall it's an fascinating paper covering both the mechanisms of aging and (some of) the best ideas we have for what can be done about it today.

 

--Dean

 

----------

[1] Cell 166, August 11, 2016

 

Metabolic Control of Longevity

 

Carlos Lo´ pez-Otı´n,1,* Lorenzo Galluzzi,2,3,4,5,6,7 Jose´ M.P. Freije,1 Frank Madeo,8,9 and Guido Kroemer
 
 
Several metabolic alterations accumulate over time along with a reduction in biological fitness, suggesting
the existence of a ‘‘metabolic clock’’ that controls aging. Multiple inborn defects in metabolic
circuitries accelerate aging, whereas genetic loci linked to exceptional longevity influence metabolism.
Each of the nine hallmarks of aging is connected to undesirable metabolic alterations. The
main features of the ‘‘westernized’’ lifestyle, including hypercaloric nutrition and sedentariness,
can accelerate aging as they have detrimental metabolic consequences. Conversely, lifespan-extending
maneuvers including caloric restriction impose beneficial pleiotropic effects on metabolism.
The introduction of strategies that promote metabolic fitness may extend healthspan in humans.
 
PMID: Not available
 
------------
[2] Adv Physiol Educ. 2006 Dec;30(4):145-51.

PGC-1alpha: a key regulator of energy metabolism.

Liang H(1), Ward WF.

Author information:
(1)Department of Cellular and Structural Biology, Audie Murphy Veterans
Administration Medical Center and University of Texas Health Science Center, San
Antonio, Texas 78229-3900, USA.

Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha is a
member of a family of transcription coactivators that plays a central role in the
regulation of cellular energy metabolism. It is strongly induced by cold
exposure, linking this environmental stimulus to adaptive thermogenesis.
PGC-1alpha stimulates mitochondrial biogenesis and promotes the remodeling of
muscle tissue to a fiber-type composition that is metabolically more oxidative
and less glycolytic in nature, and it participates in the regulation of both
carbohydrate and lipid metabolism. It is highly likely that PGC-1alpha is
intimately involved in disorders such as obesity, diabetes, and cardiomyopathy.
In particular, its regulatory function in lipid metabolism makes it an inviting
target for pharmacological intervention in the treatment of obesity and Type 2
diabetes.

DOI: 10.1152/advan.00052.2006
PMID: 17108241


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#20 Gordo

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Posted 19 August 2016 - 07:02 PM

A recent discovery of sharks that can live for over 400 years made the cover of this week's AAAS (and is the lead paper):

 

353-6300-cover.gif

 

https://www.sciencem...ongevity-record

 
Note that cold exposure is believed to be key to the sharks' longevity:

 

"...cold can also activate antiaging genes that help an animal better fold proteins, get rid of DNA-damaging molecules, and even fight off infections more effectively, extending life span. The cold-activated molecules “are evolutionarily conserved” across the animal kingdom, and thus these pathways very likely exist in these sharks, too, he predicts."


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#21 LarryFeltonJo

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Posted 13 September 2016 - 01:44 PM

This is my favorite thread over at the CR site.  As a result of it I've begun daily cold exposure (vest, cold showers, icing everything I drink).  I'm actually looking forward to winter here so that I can incorporate cold exposure into my routine outside the house.


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#22 Gordo

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Posted 15 September 2016 - 01:14 AM

I had been wondering how months of Summer heat might impact my results from cold exposure since my CE intensity is much lower than it was over the winter months.  This week we had a major heat wave where I live, and my house has been >80F all week (90's outside).  I took a couple fasting glucose readings, looks like the heat has had little to no impact.  The first was after cold shower, chipped ice drinks, and wearing the techkewl vest (9/8/16):

56.jpg

 

The next day (9/9/16), I wanted to see what would happen with less CE.  This is after a cold shower and some crushed ice drinks, but no cooling vest.  

66.jpg

There was no exercise prior to either test.

 

Some studies just published in the last couple of days:

 

Intérêt de l’exposition au froid pour le traitement du diabète de type 2

"We have shown that type 2 diabetic patients have very low levels of BAT. Most interestingly, cold acclimation in type 2 diabetes patients resulted in a very marked improvement in insulin sensitivity, although BAT activity was only marginally affected."

 

This second article contains a very nice review of many topics discussed in the more detailed CR Society thread including energy turnover, althlete's paradox, and the role of muscle ("...these findings clearly demonstrate that the significant improvement in insulin sensitivity can be attributed to skeletal muscle tissue, rather than to BAT")

 

Combatting type 2 diabetes by turning up the heat

Schrauwen P, Van marken lichtenbelt WD. Combatting type 2 diabetes by turning up the heat. Diabetologia. 2016; PMID27591854

 

"...many of the interventions that increase energy expenditure have marked metabolic health effects. Given the relatively minor effects on whole-body 24 h energy expenditure, which is often also compensated for by increased energy intake, the beneficial effects of interventions such as exercise and cold exposure cannot be attributed to weight loss... most intervention studies in which energy expenditure is elevated do show beneficial metabolic health effects without changes in body weight."

 

"...there is clear evidence that boosting energy turnover may have a direct beneficial health effect as it is underscored by studies in which energy turnover is increased by inducing mitochondrial uncoupling. Overexpression of the mitochondrial uncoupling proteins UCP1 or UCP3 in skeletal muscle increases energy expenditure and improves insulin sensitivity [2628]. Mitochondrial uncoupling can, apart from exercise training or cold exposure, also be increased by chemical agents such as 2,4-dinitrophenol (DNP)"

 

"...these results suggest that mitochondrial uncoupling, likely to lead to enhanced energy turnover, improves glucose homeostasis in rodents and humans."

125_2016_4068_Fig1_HTML.gif

At the cellular level, turnover of energy and substrates is driven by energy demand, either because ATP is needed for cellular processes or because the efficiency of ATP formation is reduced by mitochondrial uncoupling (Fig. 2). In the cell, an increase in energy use can lead to alterations in the AMP/ATP and NAD+/NADH ratios resulting in the activation of among others AMPK (Fig. 2) [5254] and sirtuin 1 (SIRT1) [55]. 

 

 

125_2016_4068_Fig2_HTML.gif

 

"...glucose is oxidised in high amounts by BAT when activated, although the direct contribution of glucose oxidation to total thermogenesis in BAT is believed to be relatively small compared with that of fat oxidation, somewhere in the range of 10–16% [92105106]. It is likely that the glucose that is taken up is mainly used for the synthesis of glycerol-3-phosphate and triacylglycerols and also for the supply of extramitochondrial ATP through glycolysis to support fatty acid esterification to triacylglycerol and other cellular functions [107]"

 

"In type 2 diabetes patients ... [cold] acclimation increased BAT activity significantly but levels were still very low [91]. Very interestingly, insulin sensitivity increased after cold acclimation by 43% on average [91]. It is very unlikely that the small increase in BAT activity could be responsible for this improved insulin sensitivity. In fact, the study showed that the improved insulin sensitivity could be explained by enhanced GLUT4 translocation in skeletal muscle in the basal state, an effect that had been previously observed in cold-acclimated rats [115] and has been confirmed in obese humans [116]. Although the mechanisms responsible for GLUT4 translocation upon cold stimulation remain to be elucidated, these findings clearly demonstrate that the significant improvement in insulin sensitivity can be attributed to skeletal muscle tissue, rather than to BAT, and may involve increased energy turnover. However, since BAT increased in all participants after cold acclimation, an indirect role for BAT (e.g. by secreting BATokines) cannot be fully excluded."


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#23 Gordo

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Posted 04 October 2016 - 09:46 PM

The steady flow of new journal articles related to this topic continues...

 

See: 

Eicosapentaenoic Acid Regulates Brown Adipose Tissue Metabolism in High Fat Fed Mice and in Clonal Brown Adipocytes

OK, we already knew that fatty acids are the primary fuel for BAT, but these guys looked specifically at EPA:  "Our results demonstrate a novel and promising role for EPA in preventing obesity via activation of BAT, adding to its known beneficial anti-inflammatory effects."  This article gets bonus points for its diagram with BAT fire ;)

 

Next:

Metabolic programming of a beige adipocyte phenotype by genistein.

What they found was the genistein was observed to play a role in the browning of fat cells.  "We conclude that genistein acts directly on adipocytes or on adipocyte progenitor cells to programme the cells metabolically to adopt features of beige adipocytes. Thus, this natural dietary agent may protect against obesity and related metabolic disease [by] promoting the development of brown or beige adipose tissue... and potentially underlies protective effects of genistein in mice."

 

Some background info on genistein:  "Isoflavones such as genistein and daidzein are found in a number of plants including lupinfava beanssoybeanskudzu, and psoralea being the primary food source,[2][3] also in the medicinal plantsFlemingia vestita[4] and F. macrophylla,[5][6]and coffee.[7] It can also be found in Maackia amurensis cell cultures.[8]"

 

Next - lets look at grains!

 

Lipolysis and thermogenesis in adipose tissues as new potential mechanisms for metabolic benefits of dietary fiber

"Dietary fiber consumption is associated with reduced risk for the development of noncommunicable diseases. The aim of the present study was to evaluate the effects of cereal dietary fiber on the levels of proteins involved in lipolysis and thermogenesis in white adipose tissue (WAT) and brown adipose tissue (BAT)...  Mice in the H-oat and H-wheat groups showed an increasing trend in serum adiponectin level. Compared with the HFD group, cereal dietary fiber increased protein expressions involved in the lipolysis and browning process. Compared with the H-wheat group, H-oat was more effective in protein expressions of PKA, PGC-1 α, and UCP1 of the WAT samples. Compared with the H-oat group, H-wheat was more effective in protein expressions of PKA, ATGL, UCP1, β3AR, and FGF-21 of the BAT samples. Conclusions: ...our results suggested that cereal dietary fiber enhanced adipocyte lipolysis by the cAMP-PKA-HSL pathway and promoted WAT browning by activation of UCP1, and consequently reduced visceral fat mass in response to HFD feeding."

 

This study looked specifically at leucine (as a reference, here's a list of foods rich in leucine many of which are already on Dean's list): 

CHRONIC LEUCINE SUPPLEMENTATION IMPROVES LIPID METABOLISM IN C57BL/6J MICE FED WITH A HIGH-FAT/CHOLESTEROL DIET

"leucine supplementation reduced the body weight and improved the lipid profile of mice fed with a HFCD. This beneficial effect was ascribed to hepatic lipogenesis, adipocyte lipolysis, and WAT browning."

 

 

So EPA, foods rich in leucine, whole grains (oats, wheat), and genistein (lupin, fava beans, soybeans, kudzu, and psoralea) belong on the BAT utility belt.  

 

Next up - have you ever wondered why BAT activity declines with age?  These guys may have discovered one piece of the puzzle:

A transcribed ultraconserved noncoding RNA, uc.417, serves as a negative regulator of brown adipose tissue thermogenesis

 

"It is well established that aging is accompanied by a decline of brown adipocyte regenerative capacity. How aging contributes to this loss is poorly understood. Here, we identify a long noncoding RNA, uc.417, which is transcribed from an ultraconserved region in rodents. Expression of uc.417 increases with age. Ectopic expression of uc.417 impairs adipogenesis and thermogenic program in brown adipocytes. However, uc.417 is not required for brown fat function. In vivo, uc.417 attenuates cold-induced thermogenic program in mouse BAT. Moreover, we find that uc.417 moderately inhibits phosphorylation of p38MAPK without affecting the total protein level of p38MAPK. The p38MAPK pathway is essential for activating BAT to stimulate uncoupling protein 1 gene expression.The data point to uc.417 as being an important factor in an age-dependent loss of function of brown adipose tissue."

 
Update on  cold exposure (CE) and cancer:  As previously described, CE has been shown to dramatically reduce cancer rates in rodents.  There are reasons to believe this observation will translate to humans as well.  Some of the likely mechanisms involved have been previously described in this thread, but there is emerging research on another mechanism.  See: "Interleukin-33, Alzheimer's Disease, Cardiovascular Disease and Cold Exposure" which describes how IL-33 is a critical component of white fat browning, and is boosted by CE:
7UgKYnA.png
It turns out that cancer has many parallels to the Alzheimers research mentioned.  A newly published article describes 

How cancer’s 'invisibility cloak' works

"How does IL-33 work?

Cancer cells genetically change and evolve. As the cells evolve, they lose the ability to create a protein known as interleukein-33 (IL-33). This protein influences another protein complex, known as the major histocompatibility complex (MHC), that act as beacons to help identify whether a given cell is a good cell or a bad cell. With these proteins working, primary tumour cells put warning flags on the outside of the cell so that immune cells recognize it and destroy it. When interleukin-33 disappears in the tumour, the flag-displaying pathway falls apart and body's immune system has no way of recognizing the cancer cells and they can begin to spread, or metastasize."

 

It remains to be seen if CE induced IL-33 production can actually affect the progression vs. apoptosis of cancer cells, but this is certainly a promising and exciting area of active research.

 


Edited by Gordo, 04 October 2016 - 09:49 PM.

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#24 Gordo

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Posted 20 October 2016 - 04:24 PM

Cold exposure boosts heart rate variability (HRV) which in turn is strongly correlated with longevity.  When I recently became interested in HRV at first I was expecting CE to actually lower HRV (since it is well documented in the literature that CE boosts the sympathetic nervous system, which by itself is an HRV lowering factor). But I heard anecdotes from others that track HRV saying CE actually boosted their HRV.  Then I began tracking my own HRV, and my observations confirmed this.  Over time I found that the more intense the CE, the higher my HRV goes.  I didn't remember seeing anything about this in any of the CE related studies I had read, so I did some digging and found this:

 

Autonomic nervous function during whole-body cold exposure before and after cold acclimation

 

What the researchers found was that cold-induced elevation in high frequency power became significant after cold acclimation, while other HRV parameters remained unchanged.  Cold exposure increased sympathetic activity, which was blunted after cold acclimation. Parasympathetic activity showed a minor increase in cold, which was enhanced after cold acclimation. In conclusion, cold habituation lowers sympathetic activation and causes a shift toward increased parasympathetic activity.

 

NOTE: Cold acclimation occurred after 10 days of subjects being exposed to 50 degree F temps (10C) for 2 hours a day.

CEHRV.png

 

At any rate, I know how to win the $500,000 palo alto longevity prize, so if any of you has access to a lab and has the credentials to enroll, I'll gladly split it with you!   ;)

 

For comparison purposes, here are HRV values from a large, healthy, physically active population:

6.png

 

 

Table 1 – Data from 10,308 Elite HRV users showing ln(rMSSD) and Elite HRV Score presented by age range and gender.

 

And here are values from elite olympians:

 

 

EnduranceVsPower-1080x510.png

 

 


Edited by Gordo, 20 October 2016 - 04:41 PM.

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#25 Gordo

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Posted 16 March 2017 - 01:15 PM

New study with a twist on catechins:

Tea catechin and caffeine activate brown adipose tissue and increase cold-induced thermogenic capacity in humans

These guys took things to a new level by adding cold exposure to the mix:

 

Before and after ingestion of the catechin beverage 2 times/d for 5 wk, cold-induced thermogenesis (CIT) after 2 h of cold exposure at 19°C [66F], which is proportional to BAT activity, was examined

 

Conclusion: Orally ingested tea catechin with caffeine acutely increases EE associated with increased BAT activity and chronically elevates nonshivering [cold induced thermogenesis] (CIT), probably because of the recruitment of BAT, in humans.

 

I don't know why I stopped drinking green tea for a while, but I am going to start back up again.  I've also read that white tea is actually highest in catechins, need to do more research to find the type with the highest levels...

 

Unrelated, but speaking of drinks...

New reason not to consume alcohol:

Chronic alcohol consumption decreases brown adipose tissue mass and disrupts thermoregulation: a possible role for altered retinoid signaling

" Our work highlights a hitherto uncharacterized effect of alcohol on BAT function, with possible implications for thermoregulation and energy metabolism in drinkers."

 

 

-Gordo


Edited by Gordo, 16 March 2017 - 01:39 PM.


#26 zorba990

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Posted 16 March 2017 - 10:46 PM

Gordo thank you for this extremely valuable and comprehensive post.
I'm happy I declined to heat my pool :-)

Any thoughts on baiba?

β-Aminoisobutyric Acid Induces Browning of White Fat and Hepatic β-oxidation and is Inversely Correlated with Cardiometabolic Risk Factors
https://www.ncbi.nlm...les/PMC4017355/

Edited by zorba990, 16 March 2017 - 11:02 PM.

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#27 Gordo

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Posted 17 March 2017 - 02:39 PM

I don't remember reading about baiba before, but a quick search does make it look quite promising.  I see its already available in 2 commercial supplements sold on amazon.  As far as the science goes, I'd love to see something that would allow for meaningful comparison to other known BAT activating compounds/foods, and especially in comparison to cold exposure.

 

Here is another study on baiba that came up in my quick search which supports yours:

BAIBA attenuates insulin resistance and inflammation induced by palmitate or a high fat diet via an AMPK–PPARδ-dependent pathway in mice

 



#28 ekaitz

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Posted 23 May 2017 - 02:44 PM

Is it possible to induce BAT by cold exposure in localized areas? or does the cold have to be systemic?

 

i.e. immersing your head in an iced water bucket? Would it increase BAT the head?


Edited by ekaitz, 23 May 2017 - 02:47 PM.


#29 Gordo

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Posted 23 May 2017 - 04:56 PM

Is it possible to induce BAT by cold exposure in localized areas? or does the cold have to be systemic?

 

i.e. immersing your head in an iced water bucket? Would it increase BAT the head?

 

Localized cooling can indeed activate BAT.  Consensus seems to be that directly cooling BAT tissue is the best way to activate it, although I don't recall any studies that really put that to the test.  I EAGERLY await a study that does comparitive analysis of cooling techniques.  The cool fat burner cooling vest targets BAT "hot spots" and has quite a bit is evidence showing it works well (I do not actually own any of their products).  The vacuum hand chiller products also locally only cool one hand but its intent is to super cool the blood which then goes to the whole body, so its not exactly "local cooling".  As far as I know, there is no BAT in the head itself (I could be wrong), however one of the prime purposes of BAT in humans seems to be to protect the brain from excess cold, so dunking your head into a bucket of ice water may indeed be an effective way to jump start BAT tissue in the neck and supraclavicular areas.



#30 ekaitz

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Posted 23 May 2017 - 09:30 PM

 

Is it possible to induce BAT by cold exposure in localized areas? or does the cold have to be systemic?

 

i.e. immersing your head in an iced water bucket? Would it increase BAT the head?

 

Localized cooling can indeed activate BAT.  Consensus seems to be that directly cooling BAT tissue is the best way to activate it, although I don't recall any studies that really put that to the test.  I EAGERLY await a study that does comparitive analysis of cooling techniques.  The cool fat burner cooling vest targets BAT "hot spots" and has quite a bit is evidence showing it works well (I do not actually own any of their products).  The vacuum hand chiller products also locally only cool one hand but its intent is to super cool the blood which then goes to the whole body, so its not exactly "local cooling".  As far as I know, there is no BAT in the head itself (I could be wrong), however one of the prime purposes of BAT in humans seems to be to protect the brain from excess cold, so dunking your head into a bucket of ice water may indeed be an effective way to jump start BAT tissue in the neck and supraclavicular areas.

 

 

Why can't there be BAT under head's skin tissue, like in others bodys skin areas? I would understand there will be less proportionally than in other areas, but not at all?


Edited by ekaitz, 23 May 2017 - 09:32 PM.





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