Tuesday, July 17, 2018

The little things that keep us going

kw: book reviews, nonfiction, medicine, cellular biology, mitochondria

Did you ever hear of a buccal smear? If you take a teaspoon and gently scrape the inside of your cheek, and put some of the stuff on a microscope slide, that's a buccal smear. The four cells in this photo are cheek epithelial cells, stained with Methylene Blue, from just such a smear.

From the scale bar you can see that the cells are around 50 microns across. They are a little compressed. A typical cell of this sort is a roundish thing about 40 microns in diameter. Methylene Blue stains DNA very well, so each cell's nucleus is seen as an oval blob about 10 microns long.

Today we are interested in something that doesn't show in this photo, the mitochondria, the powerhouses of the cell. Each of the cells above contains around 1,000 mitochondria. Mitochondria vary in size, but here they would be about the size of E. coli bacteria, a micron in diameter and 2-4 microns in length. As it happens, there are a few small bacteria in this photo, the little dots such as the one near the arrowhead labeled "Cytoplasm". Imagine about a thousand of these in each of these cells.

Let's scale this up to a size we can better imagine, and magnify one of these cells by 100,000. Some museums have made models of cells on this scale. Then the cell would appear as a lumpish thing about 4x4x4 meters in size, the size of a big bedroom with a high (12-13 ft) ceiling. The cell's nucleus would be a meter across, not quite spherical. Consider it like a bean bag chair floating somewhere near the middle. The cell isn't just a bag of fluid. "Cytoplasm" is a very complex mix of fluids and organelles. About half of the cell volume is the fluid, called cytosol; "sol" indicates it is a semifluid colloid, not just watery stuff. Just under half of the "solid" material is the mitochondria, and a similar amount of space, or a little less, is taken up by the endoplasmic reticulum (ER to its friends), a highly folded array of membranes that handle protein synthesis. There are other organelles that we won't go into here. Some can be seen in the electron microscope view on the left in the image below.


(This image is © Pearson Education.) The mitochondria scale up to be about the size of a fat sausage, such as a salami, around 10cm in diameter and under half a meter long (say, 4" diameter and a foot long or so). So now you have a bedroom with a bean bag chair suspended in the middle surrounded by salamis, and we'll have to forego describing the "shape" of the ER, except to say that it is a lot like masses of folded blankets. Mitochondria vary in shape also, from nearly spherical to long and even branched. But the sausage shape is common.

So what is this all about? Earlier this year I noticed a rather dramatic shift in my energy level. It wasn't a one-day thing, but I could think back over a few months to "how things were." My usual temperature has been 97.8-98.0°F for many years. It went to 97.6 or less, where it still is. I thought it might be one of several side effects of a diuretic blood pressure pill I had been taking for a few months. If it was, it has been a permanent side effect! I've changed to three different blood pressure medications since then, and the current one seems to have no troubling side effects. But back to energy.

Mitochondria are the powerhouses of the Eukaryotic cell. That's the kind of biological cell that makes up all multicellular life, plus protozoans and fungi, including yeast. "Eukaryotic" is Greek for "Good kernel", referring to the distinct nucleus that contains the DNA. Bacterial cells don't have a nucleus; their DNA is a long, tangled loop attached to one point on the inner cell membrane.

Knowing this, I specifically looked for a book on the subject of mitochondria and their disorders. There was really only one choice in the popular press: Mitochondria and the Future of Medicine: The Key to Understanding Disease, Chronic Illness, Aging, and Life Itself, by Lee Know, ND. Doctor Know is a naturopath, so I was a little leery, but I was cheered by the even tone and lack of hysteria in his writing. He did a great deal of research to prepare the book, which he admits is little more than an outline of many subjects related to mitochondria.

From time to time in the book the author uses a metaphor from popular culture, the Midi-Chlorians of Star Wars. They are actually modeled on mitochondria, but have the added function (in that galaxy far, far away) of tuning certain people in to The Force, so that the Jedi and the Sith have rather magical powers.

The little mitochondria in our cells have almost magical powers themselves. The first part of the book discusses their structure, activities and origins. They almost certainly began as small bacteria that were incorporated into a larger bacterium as a symbiont, on the way to the development of the first Eukaryotic cell. It may be that all cell organelles began as bacterial symbionts, including the nucleus!

Now most of the genes that produce the components of the mitochondria are held in the cell's nucleus, and turned into appropriate proteins in the cell's ER. But a small number of critical bits of DNA are kept within each mitochondrion (5-10 copies per organelle), so that crucial operations can be performed as fast as possible, in seconds or minutes rather than hours or days.

In such a complex arrangement, a lot of things can go wrong. It is amazing that most of the world's people, and plants and animals, live out their lives with little to trouble them except predation. The main reason a wild wolf seldom lives more than seven years, while a pet dog frequently lives twice that long, is that once a wolf reaches middle age, something is going to come along and kill it, frequently a rival wolf. We usually prevent our dogs from killing one another.

But why should a middle-aged wolf slow down? And…why do we slow down? On my Dad's sixtieth birthday, I asked him, "What is it like?" He said, "It is a lot like being 25, except everything takes longer." Now that I am over 70, I agree. Particularly since the beginning of this year. So the second part of the book (of three parts) describes a whole host of things that can go bad as the mitochondria wear out. The section has the cute title, "The Dark Side of The Force".

Section three, equal in size to the other two, around 60pp, describes what we can do about it. The two biggest factors for mitochondrial health? More exercise and less eating, particularly for Americans! The author really believes in Severe Caloric Restriction (though his photos show little sign that he practices it himself). Most things that go wrong with mitochondria trace back to imbalances that lead to excess oxidative free radicals such as superoxide. While there are many products that promote "antioxidants" to mop up such stray molecules, both exercise and a sparse diet (rich in nutrients, but with minimum calories to deliver them) prevent most of the free radicals from forming in the first place. They keep the "electron chain" that mitochondria use to turn ADP into ATP tuned up and running in balance.

One item that is not exactly an antioxidant, but that operates that way among several other things, and that I've heard a lot about recently, is Coenzyme Q10, or CoQ10. It is made in our bodies. But production drops off as we age, after age 30. Some medications, such as statins for cholesterol reduction, hinder its formation, further reducing it, and slowing down our mitochondria. Also, its lack possibly permits them to suffer more rapid decay. The author admits that it is hard to make this stuff into a pill that will work. It is a medium-sized molecule, and is hard to get into solution. So that's something I'll look into. It is only one of a dozen or more nutritive materials he discusses, and among them one more stands out. Magnesium. I am very thankful that this essential mineral (not known to be so essential just a decade or so ago) is added to many supplements including the calcium supplement I use. As usual with a complex machine like the mitochondrion, magnesium does several good things. Without it, several bad things can happen. For example, we think of ATP (Adenosine trophosphate) as a "thing", but this "thing" needs a magnesium ion to shepherd it around. Less magnesium, less energy.

Fortunately, magnesium is easy to get and being a "salty" element it is easily absorbed. A magnesium atom sits at the center of the heme complex in chlorophyll the same way an iron atom sits in the heme complex of hemoglobin, which makes our blood red. The magnesium makes the heme green in plants. The greener the plant, the more magnesium. So eat yer darn greens! (By the way, hemocyanin, the heme complex with a copper atom inside, makes the blood of crabs blue. The "cyanin" part of the word refers to the blue color, not to cyanide).

There you have it. I'll keep a lookout for newer books on the subject. At present, this book stands out, and while it contains a lot of technical language, it is well explained, so the book is easy to read.

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