Intermittent Fasting, Cell Plasticity, and Your Nervous System

This year, throughout my endeavors, I've come to notice that C. elegans studies are everywhere, and being published all the time. I recently came across a project, done with C. elegans of course, that found a causal relationship between intermittent fasting and longevity. Here, the team focused on the conformations of mitochondrial networks in cells with respect to energy demand. In usual circumstances, cells lose this ability to change as they age - they become less plastic, if you will. This would mean then, that constant change in the mitochondrial structures and their networks means the cells are younger and a decreased ability to change shape implies aging. The question then became, if the cells are experiencing vastly fluctuating energy demand vs. supply dynamics, how do those extremes affect the cells' ability to manipulate mitochondrial networks?

And that's where the C. elegans came in - biologists replicated dietary restrictions by genetically manipulating the levels of an energy-detecting protein called AMP-activated protein kinase (AMPK). Basically, this protein is a form of energy that lacks two phosphate groups. You're probably familiar with ATP (Adenosine TRIphosphate) which stores energy through the tight bonds between phosphate groups in the compound. AMP (Adenosine MONOphosphate) is basically an ATP molecule waiting to happen. It doesn't have multiple phosphate groups to store energy in their bonds but it has the potential to do so given that it is phosphorylated (donated phosphate groups) by a kinase complex.

So essentially, by changing the amounts of AMPK in the cells, they were constantly re-configuring into different mitochondrial networks because there wasn't a constant level of energy accepted into the cells. Thus, it was shown that these cells because they were continuously undergoing dynamicity, aged at a slower pace than cells which did not have intermittent fasting imposed upon them. Of course, it's important to take these findings with a grain of salt. Just because one may be changing the incoming energy levels for their cells doesn't mean it doesn't matter what you eat. And also, not everyone's physiology would respond in the same manner. People who have blood-glucose imbalances must constantly be providing a steady level of energy from food in order to preserve a very fragile homeostasis in that respect.

I know this doesn't really have anything to do with C. elegans in neuroscience research but I share this study with you here because it got me thinking about neurons doing the same thing - constantly changing - and how the glial cells take on such a role. Before I discuss that though, I think it's important to take note of the different meanings the word "plasticity" can possess when speaking about different types of cells in an organism. In the peripheral tissue cells of the C. elegans, plasticity means that the mitochondrial networks are changing shape. In the nervous system, however, we've understood plasticity (neuroplasticity) to mean the changing of networks between entire neurons - individual cells - as opposed to several organelles within the same cell.

It is a given that with an aging brain, comes a decrease in neuroplasticity. This is shown not only in educational studies exploring how people of different ages learn, but also in neurological studies, observing functional MRIs of cognitive abilities and responses to external stimulation. In C. elegans though, the small number of neurons means that each nervous system cell takes on multiple roles throughout the short life cycle. Let's consider glial cells, those are what I am studying after all. At the larval stages of its life cycle,when the nematode is very young, the glia are responsible for specializing each neuron to its specific location and process. Then, when the nematode reaches the L2/L3 stages, the glia begin to act as moderators of substances and keep the nervous system in balance. Lastly, as the nematode arrives at full adulthood (L4 stage), the glia combine to form a sheet-like coating around the nerve ring. These four cells then become known as CEP sheath cells. Here, the neuropithelial tissue serves to regulate axon growth and specification for the remaining life of the worm. I knew a lot of this information from reading about it in articles and books, but it wasn't until I was actually looking at the glial cell under the microscope that I came to understand what these fluctuating functions mean.

I will try my very best to describe this amazing image but if all else fails, just take a look at the picture below. So under the fluorescent microscope, you can see the glial cells very brightly, like four (green) light bulbs in the anterior portion of the worm. If you focus the image really really well, and of course, get over the excitement that you're looking at a glowing worm (!!), you'll notice that also illuminated in green is a slightly rounded line stretching from each of the glial cells to other neuronal axon endings. These are called axonal processes and they stretch from the glia to sensory neurons at the end of the nerve ring. Over time, these connections change in conformation, much like the fluctuating mitochondrial networks mentioned earlier, to accommodate the simultaneously changing neuronal networks in the rest of the nervous system.

So, what does this mean for us? To be honest, I don't think that the answer I have read about and formulated is all there is to it, but nonetheless, let us proceed. Constant change is important because it keeps our cells, organelles, and networks youthful. The ability to change is the ability to propel oneself forward, both biologically and metaphorically. For all I know, this could mean that preventing Alzheimer's involves a crazy dystopia of extreme neurological circumstances induced by a helmet you buy at CVS. The point is, it doesn't seem like the largest breakthrough or even a breakthrough at all, but to understand how our cells deal with changes and how that affects them in the long term is of monumental value. Remember, understanding the larger things always always requires an understanding of the smaller pieces.

My dad often tells my siblings and I whenever we're on break or during the summer time, "do something that makes you think - you don't want your brain to get rusty." Despite the amount of times I've rolled my eyes and laughed at such advice, there is some truth in that. Constant activity means constant change, and constant change ensures that the ability to change is preserved.