April 25, 2014 | 14
After a teenage stowaway flew from California to Hawaii hidden in the wheel well of an airplane this week, investigators immediately began to wonder how he had survived the freezing temperatures and low-oxygen conditions of the unpressurized compartment.
The latest theory is that he fell into a state of hibernation – an entirely plausible scenario, if you ask me.
How do I know this? Well, I study the closest genetic relative of humans known to hibernate. The only primate to do so, the dwarf lemur of Madagascar spends up to eight months of the year in hibernation—an astounding feat, especially for a primate.
Hibernation is an extreme survival tactic that some mammals living in seasonal environments use when resources disappear and threaten overwinter survival. This radical deviation from normal physiology involves a whole gamut of bodily systems gone haywire: heart rate is nearly arrested, body temperature plummets to near or below freezing levels, and brain activity virtually ceases. Hibernating animals look dead.
The heart rate of an active dwarf lemur is around 180 beats per minute, but during hibernation it can drop to as low as four beats per minute. Body temperature, which usually hovers around 36 degrees Celsius, can plunge to almost freezing at a frigid 5 degrees C. And I’ve recently witnessed a hibernating dwarf lemur go 21 minutes without taking a breath. (Warning: Don’t try this, unless you happen to be holed up in a wheel well of an airplane).
Many of the physiological changes that happen during hibernation would be fatal to non-hibernating species. Yet dwarf lemurs master these changes successfully during the hibernation season, year after year after year.
This gloriously weird physiology is displayed in an animal that shares about 97 percent of our genome. But here’s punch line #1: As the Hawaii stowaway demonstrated, humans might already have the mechanisms that confer the ability to hibernate present in our genome.
Hibernation biologists now believe these extreme modifications of normal physiology are due to underlying changes in gene expression. Think of this as analogous to a very sophisticated light bulb. This light bulb requires multiple switches to be flipped on for light emission, and only the correct combination of switches will suffice. The light bulb in this example is the hibernation response (i.e. if it’s lit up the animal is hibernating) and the light switches are the genes involved.
To put it in the context of dwarf lemur hibernation, here is an example: Preceding hibernation, dwarf lemurs get fat. Excessively fat. As fat as they can manage given the food resources available, sometimes more than doubling their body weight all in a matter of little over a month. And they store this fat in their tails.
During the rainy season, their habitat is replete with food and the animals are gorging themselves on fruit and insects—normal carbohydrate metabolism chugging away. Those genes that drive carbohydrate metabolism are flipped on. Then the extreme dry season hits and resources disappear. Dwarf lemurs enter hibernation and since they can only rely on stored fat in their tails to keep the critical physiological processes running, the combination of genes that govern fat metabolism flip on. This leads to a breakdown of fat reserves, which fuels the body during a time of fasting.
In the early 1990s, scientists investigating biochemical changes during hibernation in ground squirrels—a model laboratory hibernating species—documented the first gene exhibiting differences in expression levels between ground squirrels’ active state and when the animals were deep in hibernation. This gene, α2-Macroglobulin (α2M), which functions to inhibit blood clotting, displays higher levels of expression when an animal is hibernating relative to the animal’s active state. This is especially important for survival during hibernation as circulation is nearly arrested due to a reduction in heart rate, increasing the potential risk for fatal blood clots to form when circulation slows down.
Remember back in chemistry class when you learned that the lower the temperature, the slower the reaction time would be? Well, when core body temperature is lowered to a few degrees above freezing during hibernation, it follows that fundamental cellular and physiological processes would slow down in response. Punch line #2: They don’t!
The discovery that specific genes, like α2M, are increased in expression during hibernation instead of being decreased as expected means that cellular reactions are still happening despite chilly body temps. This indicates that these molecules must be important for survival during hibernation. Differentially expressed genes could provide vital clues to metabolic functions that are imperative for survival during hibernation, such as fueling a hibernating animal solely through lipid metabolism.
With next-generation sequencing technologies to scan the entire genome for the changes in gene expression that correlate with “physiology gone haywire,” hibernation biologists can compare across the hibernating species and see if similar genes and genetic pathways are responding. Punch line #3: Similar patterns are seen in ground squirrels, black bears and little brown bats—hibernating species that represent a wide-range of the mammalian family tree.
While we don’t know if these patterns hold true for all hibernators, comparable findings in very distantly related mammal species suggest that all mammals, including humans, might already hold the genes needed for hibernation. The next step is to look at the genetic mechanisms regulating dwarf lemur hibernation, our closest hibernating cousin.
Further investigations using animal models (like dwarf lemurs that can survive extreme physiological changes during hibernation) may lead to breakthrough medical treatments to improve the human condition.
For example, understanding the mechanisms of how peripheral tissues withstand insufficient blood flow during hibernation might lead to better technologies for protecting the brain during a stroke or some form of trauma. By figuring out the ways in which hibernating animals avoid atrophy after not using their muscles during eight months of hibernation, researchers might better the lives of immobilized or bed-ridden humans. Dissecting how animals in hibernation can rely solely on stored fat as fuel will indeed have immediate benefits for understanding obesity and other metabolic disorders.
Lastly (and most excitingly for science fiction nerds like myself), figuring out ways to induce humans into a hibernation-like state might make it possible to launch humans into far-flung galaxies, as glorified in popular sci-fi movies like Alien and Prometheus.
When it comes to air travel here on Earth, however, an economy-class ticket is still the best way to go.
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