We take a quick break from our macronutrient discussion to talk about some really exciting news in the hypothermics world that showed up in the last two weeks. It’s great when new data shows that old thoughts might be wrong.  This one comes from researchers at Harvard Medical School (and a host of other institutions).(1)  These scientist discovered a new hormone, irisin, named after the greek goddess iris – the personification of the rainbow and messenger of the gods.

What is most exciting is that this hormone could be another piece of the “calorie” controversy – the irritating paradox of calorie in, calorie out.  So let’s take a look at what they found.

Only the Good Die Young

In the past we have discussed the role of the uncoupling protein, UCP1, that instructs the mitochondria to generate excess heat instead of producing ATP.  This protein is mediated by another very important co-activator, PGC1-α. You may have heard about it in connection with what are called the Sirtuin proteins. If not, let’s back up and review a little on these before getting into this new discovery.

By regulating the production/activation of this family of molecules, scientist have not only been able to vastly alter obesity in mammals, they also are able to affect animal longevity.  You’ve heard of Resveratrol by now and these are the very same metabolic pathways altered by that molecule. (2-4)

For example, if you look the the photo to the right, you’ll see a pair of mice. One mouse (left),  was genetically modified to have enhanced PGC1-α and compared to a normal control mouse (right).  Just a scan of the photos and you will quickly see that the modified mouse ages “gracefully.”  Its control cage-mate gets plump like the rest of us even though it’s in the same environment. The genetically modified mouse stays healthy.

It doesn’t stop there. Take a look at graph “E” to on the bottom right.  That is the difference in performance of Treadmill tests (I wonder if they used Livestrong?).  Look at the difference of performance at 22 months! Like a fine red wine, these mice get better with age.  In addition to the lack of weight gain and increased running skills, these mice showed no age-related bone loss or insulin resistance and the typical systemic inflammatory response was mitigated.

Despite what people might say, you’re not going to get these results from drinking red wine (sorry), but these are incredible first steps to unlocking the mystery of aging and metabolic syndrome.

Message to My Blubber

The new research identifying the irisin hormone is just as exciting.  This hormone was hidden as part of a much larger molecule and these researchers were able to  isolate it.  Irisin is secreted as a result of exercise in both these transgenic (modified) mice and Humans.  It turns out that this is way for the muscle to “communicate’ with the forming white adipose cells, signaling them to become the more energetic brown adipose tissue (BAT).  The concentration of this hormone jumped sharply after exercise (Human and mice).

The researchers went a step further.

By doing experiments in cultures, they discovered that nano molar levels (tiny amounts) of this hormone cause a 50-fold increase in the UPC1 protein. When delivered in vivo (in the animal) they still saw a 10-20 fold increase of in UCP1, which resulted in an increased energy expenditure and improvement in the glucose tolerance of mice fed a high fat diet.  But a nagging question remained. What purpose would be served by a hormone being released in response to exercise that INCREASED energy consumption?  One might thing that the opposite would be true – evolution would dictate conservation of energy.

Cavemen Didn’t Exercise

A long time before 5-toe shoes and grown men (and women) running through NYC Central Park beating their chest and throwing boulders, we were far more like the bird sitting on your back porch (unless you are looking at a pigeon – they don’t count); we starved.  If you look all around you and ignore domesticated animals (including pigeons and rats), you will find that every animal is starving.  They live to eat every day and it is a struggle to find calorie.  It is THE struggle that anthropologist are still trying to unravel with Humans.

Where did we get the energy to become the modern-day intellectual giant?

You should see the conflict. If we were starving and now find that a hormone is released in response to strenuous activity, which turns energy storing white fat into energy burning brown fat, that would be a NEGATIVE not a positive evolutionary trait. The quest to find food would be a downward energy spiral.

Ah, but we really had no reason to run through the park or roll giant tires around. Why would our ancestors need to exercise?  It turns out that there is one activity that WOULD cause a lot of muscle activity, yes it’s shivering.  It was a way for animals to keep warm and in response to the biological stress of cold, muscle secreting a hormone to create more BAT to keep warm was a GOOD thing.  It meant staving off hypothermia.

A further interesting fact is that PGC1-α was originally discovered by scientists, because it was unregulated by cold exposure.  We also know that in addition to caloric restriction, mild cold stress is the only other way that we have demonstrated longevity in mice. Even more exciting is that recent tests (unpublished) have show a nearly 5-fold increase of BAT output of a 52 year old man vs 20 year old controls.  This increase was even though they had similar levels of BAT, so there is even more energy to tap into. You can adapt and cause increased metabolic activity.

Un-wrapping it All

I think we are seeing just the tip of where all of this is going. In the last decade we have moved from the idea that we lose all of our BAT with aging, to we have a fixed amount of BAT, to now understanding there are hormonal mechanisms to create new BAT.  Further the exact pathways that are responsible for longevity through caloric restriction also are affected by mild cold stress.  These systems respond to biological stress of starvation and cold, like a muscle responds to the stress of weight training,  by creating a more resilient biology.

Mild cold stress does not have to be miserable, or even cold.  It can come in a lot of different forms. In the David Agus new Book, The End of Illness, he discusses at great length the role of inflammation in aging. He even gives an example of a one of his “all-star” cancer patients. Diagnosed with prostate cancer at the age of nearly 80, he decided to make a life changes that include swimming every day. He is now almost 90 and doing incredible.

I have documented the profound ability to thermal load through swimming.  In addition we know that mild cold stress starts in warm water (27C/80F).  Today we have learned that a hormone has been identified that is not only increases PGC1-α, it’s causes all the benefits of longevity seen through sirtuin activation. It’s exciting to see this all come together and I know we’ll only learn more. This is not the ice cube diet or really even “freeze your ass off,” it’s a basic adaptation with millions of years of evolutionary excellence.

Turn the heater off, go for a walk, let go of a few layers, move,  or just swim – do something.  You have nothing to lose and we all look funny as hell in shorts, gloves and face masks.  If laughter is the best medicine, worse case is you’ll make someone live longer by laughing.

Ray

 

(1) Boström PA, et al.,  “PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis,” Nature. 2012 Jan 11. doi: 10.1038/nature10777. [Epub ahead of print]

(2) Wenz T, et al. “Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging,”Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20405-10. Epub 2009 Nov 16.

(3) Tong Shi, et al. “SIRT3, a Mitochondrial Sirtuin Deacetylase, Regulates Mitochondrial Function and Thermogenesis in Brown Adipocytes,” J. Biol. Chem., Vol. 280, No. 14, Issue of April 8, pp. 13560–13567, 2005

(4) Marcia C. Haigis and Leonard P. Guarente, “Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction,” Genes Dev. 2006 20: 2913-2921.

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Ray