The body's response to fasting, part 4: in which I actually write about fasting

Well, here it is. To be honest, I'm a little intimidated. I've set this up; now it's time to bring it all together. I guess the best thing to do is take a deep breath and jump in. I should warn you, though, this is going to be a long post.

First, a little disclaimer. I haven't consulted a lawyer, so I don't know if this actually increases my chances of avoiding liability. But even so, it's probably something I should make clear anyway. While I have a fairly strong background in biology, I'm not a health care professional. The purpose of this post is to present certain biological facts and comment on their possible implications for our lifestyle choices, not to give people medical advice.

An important player in the body's response to fasting is a deacetylase called Sirtuin 1 (Sirt1). One of of the functions of Sirt1 is to deacetylate histones, which you'll recall from previous posts changes the cell's pattern of gene expression. But Sirt1 is a busy little deacetylase; it also deacetylates many proteins other than histones, thereby altering their molecular structures and functions. Between the proteins whose gene expression Sirt1 controls via histone deacetylation and the proteins whose function Sirt1 directly affects via deacetylation, Sirt1 has been implicated in functions including metabolism regulation, insulin signaling regulation, cell survival, neuroprotection, cancer prevention, and longevity. And Sirt1 activity is increased by ... fasting! There, as promised I have finally brought this topic around to directly addressing the subject of fasting.

There is one more cellular activity that Sirt1 has been implicated in, and I think it deserves its own paragraph: autophagy. Autophagy is when a cell digests its own molecules or organelles. This may seem like something you wouldn't want your cells doing, but it's necessary for recycling resources that would be better used elsewhere, maintaining a healthy immune system, retiring damaged molecules and organelles, and breaking down proteins that are prone to aggregation (such as the amyloid deposits characteristic of Alzheimer's disease). And this process occurs most efficiently when the body experiences periods of food deprivation. We're just not built to be perfectly well-fed at all times.

So, I've thrown all this information at you about what happens when you fast. Now we all have to decide what to do with that information. At this point I would like to do the responsible thing and tell you that if you want to experiment with fasting in your life, you should consult with your physician. The problem with that is I've talked to many physicians. Most of them don't actually pay that much attention to you when you talk. Most of them have a very limited set of routines they apply to any given problem or question, with very little real problem-solving going on. Very few of them seem to examine the body of information available to them and make well-considered evaluations of the situations presented to them. So I suppose the responsible thing to tell you is first find a physician you trust to use their brain, then consult with them about fasting.

I would also like to point out that while there is a large body of evidence for the benefits of fasting, the same can't be said for how to go about fasting. There are a multitude of fasting regimens out there, and there is little agreement about which one is best. When I wasn't sick, Noel and I enjoyed a routine of fasting on the four quarters of the lunar cycle: full moon, the two half-moons, and the new moon. It let us take something that was good for our bodies and tie it into the larger cycles of the earth. There, after spouting science at you for weeks, I finally said something remotely Pagan-ish. Aren't you happy?

Here's another responsible thing I would like to say, but can't say it without some explanation. I would like to tell you to listen to your body, but that can be tricky when it comes to fasting. Our bodies have adapted to periods of food shortage occurring naturally. All our instincts tell us that if food is available, we should eat it. This would be fine, except that now food is available all the time (I'm making the dubious assumption that if you have access to a computer you have access to food; probably not completely correct, but it probably applies to most of you), but there is significant evidence that it's not healthy to eat all the time. So in order to successfully fast, you have to fight your body to some extent. In fact, all the accounts I have ever read or heard from people who have tried fasting have said that they felt awful until their bodies adjusted to the routine. So listen to your body to some extent, but also keep in mind that fasting is probably not going to feel "good." In fact it could very well feel the opposite of good.

It's also important to remember that water deprivation reaches the deleterious stage much faster than food deprivation, so you absolutely don't want to restrict your water intake. On the other hand, you also have to be careful not to overdo it. Fasting means you're not bringing electrolytes into your body, and an electrolyte imbalance brought on by too much water and not enough calcium, magnesium, potassium, and sodium is nothing to mess around with.

While we're talking about nutrient balance, a lot of the benefits of fasting have been observed regardless of what the quality of the rest of the diet was like. That being said, it's my opinion that fasting shouldn't take the place of making nutritionally balanced food choices. In fact, Sirt1 requires a molecule called nicotinamide adenine dinucleotide (NAD+) to function, and the easiest way for us to synthesize NAD+ is using niacin - an important dietary nutrient found in a wide variety of foods. Also keep in mind that "nutritionally balanced" may not be what our popular culture assumes it is. I would definitely recommend that we all do some research along those lines.

Now, as if things weren't complicated enough, I have one more twist to throw into the mix. Any statements I have made about the effects of fasting apply to healthy animals with a normal genetic makeup. In fact, there is some evidence that certain genetic variations can cause effects opposite to the ones I've described. So if you have any infection, disease, or genetic abnormality, do not mess around with your health. Find a physician you trust to use their brain (see above), and let them help you figure out if fasting is something you should try before proceeding. You'll notice I mentioned that I fasted when I wasn't sick. Now that I'm wrestling with the aftermath of a nasty virus, I've been avoiding fasting because I don't know how it could affect my recovery. Fasting puts the body into breaking-down-molecules/releasing-energy mode, and to heal from an illness you need your body to be in building-up-molecules/storing-energy mode.

The same thing applies to children. Children need to do a lot of molecule-building, and fasting (beyond missing a meal because they turned up their noses at your dinner) could be disruptive to those processes. So I would be very leery of anyone fasting who has not reached full physical maturity. And by extension, I would also avoid it if I were pregnant.

Whew! I finally got it all out. Now I have to figure out what I'm going to write about for next time. If anyone has any suggestions, feel free to share them. Also, happy holidays!

Next post: Tuesday, December 25

The body's response to fasting, part 2: gene expression

Since I haven't gotten any input to do something else, I'm going to stick with my plan to write about gene expression today.

The very quick, simple explanation for how gene expression works is that a sequence of DNA is transcribed into a sequence of RNA, and that in turn is translated into a sequence of amino acids - a protein! But it's the details of that scheme that make it such an interesting process. To begin with, what does the transcribing? RNA polymerase - another protein! As I mentioned last time, the behavior of proteins is controlled by the other molecules they interact with. This is especially important for RNA polymerase, because if it didn't have controls, it would just transcribe as much of one chromosome as it could before dissociating, and what use would that be to anyone? It would be chaos. This is prevented by the fact that RNA polymerase can't attach to DNA and start the transcription process by itself. It needs the assistance of other proteins, called transcription factors.

 What makes this whole thing work is that DNA is not just a sequence of symbols, as you've often seen it characterized. DNA is a long molecule with it's own physical properties, and different sequences of DNA have different physical properties. One of those physical properties is affinity for proteins like transcription factors. So a gene consists of the sequence that is transcribed into messenger RNA and a sequence with an affinity for certain transcription factors, which in turn assist or hinder RNA polymerase with beginning the transcription process.

Like most proteins, transcription factors are themselves very sensitive to their environment. Aside from only having an affinity for specific sequences of DNA, their affinity for those sequences is also increased or decreased by interaction with other molecules in the cell. Certain cellular conditions change the affinity of transcription factors for their regulatory sequences of DNA, and that in turn changes which genes are being transcribed into proteins. This change in gene expression can in turn change the cellular conditions, and the whole regulatory process continues. This means that your body is constantly changing its chemical makeup in response to its current situation. I find that very exciting.

My plan for next time, unless I get suggestions to do something else, is to get into some more advanced protein and gene regulation. It's all completely necessary, I assure you.

I also realize that most people don't consider Wikipedia to be a serious reference. While that may be true, it is a great place for people with a variety of backgrounds to get a lot of basic information on a topic. So please don't think less of me for referring my readers to Wikipedia for additional information on these topics.

Next post: Tuesday, December 4

The body's response to fasting, part 1: proteins

I apologize to those of you who already understand all this thoroughly, but judging from my conversations with Noel, it seems like the best plan is for me to start with basics. And no, the irony of writing a series of posts on fasting during the Thanksgiving/Winter Festival of Your Choice/New Year season is not lost on me.

I sat and stared at my screen for quite some time just now, because there are several ways I could launch into this. After much deliberation, I've decided to jump in with proteins, because almost everything that goes on in our bodies has a protein behind it. Considering the variety of activities that go on in our bodies, it might be surprising to find out that one family of molecules is behind all of it. This is because proteins are polymers - large molecules constructed by stringing together smaller molecular units. In the case of proteins, these units are amino acids.

The great thing about amino acids is that part of the molecule is the same for every amino acid (called the backbone), and part of it varies from molecule to molecule (called a side chain). The backbone is the part that gets linked to other amino acids. Because that part is the same for all of them, they all get linked together the same way. The side chain determines what chemical properties the amino acid has, and therefore what chemical properties the protein will have. The proteins that they comprise are huge - hundreds or even thousands of amino acids linked together. So as you can probably imagine, it's a difficult task figuring out how the properties of all these individual amino acids come together to produce the chemical properties of the whole protein. It's something we're still working on figuring out, but we're gradually making headway.

The huge size of proteins makes them very sensitive to their environment. Each amino acid side chain is like a little feeler, interacting with the surrounding water and salts and sugars and other proteins and all the other molecules that are floating around in their body. Each side chain (or group of side chains that end up next to each other in the protein structure) is attracted to certain molecules and repelled by others.

To make things even more interesting, amino acid side chain within the same protein interact with each other. So every protein has a distinct shape. Many of them have dense cores at the center of the structure. They form grooves and pockets that are well suited to housing certain molecules. They form long fibers. They form protruding knobs that can latch onto other molecules. They form things shaped like hairpins. So many different shapes!

Ready for things to get really interesting? The sensitivity of proteins to their environment combines with their tendency to make distinct shapes to create distinct shapes that can change depending on the specific environment! Emergent properties, baby! Have I mentioned that I love biochemistry? It blows my mind!

Ok, now that I've gone over why proteins are not only important but also amazing, my plan for next time is to get into gene expression and how proteins are involved in that. However, if there's something that's still a little fuzzy from this post that you'd like me to go over in a little more detail instead, let me know. Likewise, if you already understand gene expression just fine, thank you very much, and you'd like me to pick up the pace a little bit, you can let me know that, too.

Let the late fall/early winter festivities commence! But don't get too carried away, because your proteins are watching you ...

Fasting - some preliminary notes

All right, so here's my plan. I would like to write a post about fasting. It is a subject that has fascinated me for a long time. When I was in my early 20s, I really wanted to be an ascetic. I think I thought it would make my life easier. Anyone who knows me well will attest that that definitely did not happen. Neither the part about becoming an ascetic nor the part about my life being easy. Easy is overrated anyway. Now, there seems to be quite a bit of evidence piling up that our bodies aren't meant to be perfectly well-fed all the time.

However, I would really like to do this topic justice. I don't want to take a cool topic like this and spend thirty minutes talking out my butt, not really saying anything useful. So, that's what I'm going to be doing until you hear from me again. I'll be preparing to give you (I hope) a really useful article on the subject of fasting. I hope you find it as interesting as I do.

Next post: Tuesday, October 30

Our physical existence

If you accept that there is a spiritual dimension to reality, what does that say about the physical side of our existence? It seems like a lot of people want to consign physical existence to a secondary role in this universe, as if having a spiritual existence somehow makes the physical one less important. I tend to think the opposite. I think of physical existence as a very important place; namely, a birthplace for new spirits.

If you look at the world from a very animistic point of view, everything with a physical existence has a spirit (or at the very least, has spirit). From that point of view, as the physical world gains complexity so do those spirits. This world is a cradle and nursery for spirits.

You could also argue that this world is a workshop for them. This world, with its physical rules, could provide a framework for spirits to interact with their universe. It could provide a forum for negotiation with other spirits. Perhaps it's just my meat-brain talking, but I find it difficult to imagine manipulating reality on a purely spiritual level. It seems to me that physical existence would provide a good "handle" for these interactions.

So, there you have it. Some interesting things to ponder if you get bored this weekend. I'll write some more on Sunday, September 16.

Why I'm polytheistic

With so much of the world's population following monotheistic religions, it might seem strange to some that I would choose to be polytheistic. Today I'm going to explain why I did. Why do you care? Frankly, maybe you don't. But as I've said before, I can't speak for all people and all times. All I can do is share my own personal perspectives. Maybe they will resonate with you; maybe they won't. So today I'm going to share my personal journey toward polytheism. Enjoy (or not - it's up to you!)

This could be a really long story, but I'm going to shorten it considerably by condensing the first part of it. I was raised as a monotheist, I became an atheist/agnostic, then discovered that try as I might to reason it away, there was a spiritual facet to my identity that I just couldn't ignore anymore. So I accepted myself as a spiritual being. There, long story made short.

Once I had accepted myself as a spiritual being, I was left with the question of what exactly I was going to do with that. Now, this is going to be one of many posts in which you get to see the scientific and mystical parts of me intersect. I was guided by the concept of entropy.

Entropy is a concept that encompasses many things, and trying to define it is a great way to fire up a debate with anyone with any exposure to physics. But I'll just briefly and simply explain entropy as a "lack of directedness." For example, in a collection of gas molecules you'll have about as many molecules going one direction as there are going the opposite direction. That system has a lot of entropy. It is a property of the universe that entropy increases, which means that every system gradually loses its ability to make a directed change to the universe. And as far as I know there's no way around it; entropy has a very interesting relationship with probability. If you sit down and do some fun mathematical exercises, you will reach the conclusion that entropy is maximized when the most probable event occurs.

Now let's look at this from a spiritual perspective. We all exist in a system that is gradually running out of "steam". From a monotheistic perspective I would have to look at God at this point as say, "What the fuck? You made all this; was the expiration date really necessary?"

From a polytheistic perspective, there's no other way the universe could work. If there are multiple gods or spirits that created this existence, no one of them could exert her will perfectly on it. With every event that occurs, each one leaves his mark but also yields to others who leave their marks. That yielding of complete autonomy becomes the price of admission for participating in this great endeavor that is the universe. Entropy increases.

PS: A lot of bloggers make a point of posting once a week on the same day. I understand why they do that; people are more likely to read your blog if they know when to expect the next post. Checking a blog takes time and attention, so why check it if you don't know whether there's anything to see? The problem with that is I really don't like doing the same thing on the same day of the week. It drives me nuts. So I'm going to compromise, and every time I post something I'm going to decide when the next post will come out and let you guys know when that is. You guys get some reliability, and I get to mix things up a little. So here you go - I will post again on Friday, September 7th.

This has the added benefit of motivating me to write. I've made a commitment now, so I'm much more likely to follow through!

PPS: I can't do the same for Noel; I do not control when he posts here.