Thursday, 26 January 2012

Untidy Houseguests: How Our Bacterial Powerhouses Might Be Slowly Killing Us

"When our ancient eukaryotic ancestors decided to take in bacterial boarders, it seemed like a pretty good deal, as they were good at stoking the furnaces. Alas, they did not foresee the possibility that these creatures, which became our mitochondria, might also create some household problems." - George M. Martin, "The biology of aging: 1985-2010 and beyond"

The opening quote is a line from a really good review of aging which I heartily recommend. I also included it because it's actually a good way of introducing the concept of mitochondria.

Meet your (literal) fuel cells
 The leading theory on the origin of mitochondria is that at some point in evolutionary history, a bacteria was absorbed into a larger cell, and survived the process. The bacteria then became a part of the larger cell because it allowed an evolutionary advantage of providing energy to the cell, in a process which I'll now explain.

As you can see in the image above, mitochondria have a quite complex construction. As with many cells, mitochondria have an inner membrane, an outer membrane, and a gap between the two referred to as the intermembrane space. The lines you can see stretching across the mitochondrion are infoldings of the inner membrane, and are called cristae. The area inside of the mitchondrion is called the matrix. The small black circles are granules, which aren't particularly involved in the energy process.

As we all know, when eat food, our stomachs break it down into more basic parts through digestion. But where do these parts go? Glucose, which is a simple sugar, moves into the glycolysis pathway. This involves several different enxymes breaking down and altering glucose into a number of different forms until it becomes yet another molecule, acetyl Coenzyme A, which is commonly referred to as acteyl CoA. This molecule then moves into a new cycle called the Citric Acid Cycle, which takes place in the matrix of the mitochondria.

 As you can see, this cycle takes in the acetyl CoA molecule and uses it to convert many compounds into high energy compounds, such as ATP and NADH. These compounds are then used throughout the body as a sort of energy currency, fuelling the various processes needed to keep you alive. 

Unfortunately, this process isn't perfect. An unwanted by-product of this process is the release of electrons. Normally, the mitochondria can reabsorb these electrons to be used in different cycles, but occasionally they can be leaked out into the cell. The result is the formation of reactive oxygen species. These molecules can cause serious damage to both the DNA of mitochondria and the cells of the body, which can lead to mutations. These mutations can lead to further leakage of electrons and this leads to further... You see where we're going with this.

So are our fuel cells to blame for ageing as we know it? Hard to say. The electrons that initially leak out tend to be the result of mutations in the DNA, which can occur randomly over time. However, mitochondrial ageing could actually be a RESULT of a different theory of ageing. What if, for instance, the decay of telomeres discussed in the previous post caused the mitochondrial leakage? What if it is something else entirely? It is difficult to say whether the damage of free radicals is a cause or effect of ageing.

You'd be amazed at how often that happens in Biology.

Wednesday, 18 January 2012

Telomeres: How Your DNA is Like A Shoelace

At some point, you've probably noticed those little plastic doodads at the end of your shoelaces. Apparently, they're called aglets. These little caps serve to hold together the laces at the end to prevent them from fraying apart over time. It might sound strange, but your shoelaces are a bit like your DNA.

Pictured: DNA (not really)
 DNA, in its most basic form, is a long strand made up of the bases adenine, thymine, guanine and cytosine, which are typically represented by A,T,G and C. The strand exists in a double helix structure, where each base is paired to its appropriate match (A to T and C to G). 

Here, we see the DNA base pairs, as well as DNA in its natural form, the double helix.
When the cell must divide, the DNA is peeled apart, and appropriate base pairs are added to either strand. The result is two identical strands of DNA, which are then separated into two new daughter cells. Perfect.

Except... that's not quite the case. Unfortunately, the DNA replication process isn't quite perfect. Every time the DNA divides and is replicated, a few bases are lost off the end of the strand. That's where telomeres come in.

Doesn't look like much, but these things keep your  DNA safe

Telomeres are lengths of repetitive DNA that have no function other than to be missed out in replication. They do not code for anything when the DNA is read by the ribosome, so if they are not present, then the cell, and by extension the body, can still function normally.

What the telomeres do provide is a sort of bumper zone for the DNA replication failure. As previously stated, the replication chops a few bases off the end of the strand each time. If the bases being missed coded for important proteins, then missing them could potentially kill the cell. If this happened in all the cells of the body, then it would barely be able to support itself. However, removal of sections of the telomeres causes absolutely no negative effects towards the cell. If the bases that are missed are from the telomere, the cell can continue functioning as per normal.

So how does this cause ageing? Well, the telomeres are absolutely fine being missed out during every division, but unfortunately, there's only so many times this can happen. Over time, the telomeres are degraded, until eventually there is nothing left. At this point, the bases missed off by replication ARE crucial to the cell. The cells then fail to divide, and slowly, the rate of cell death rises. How does this manifest itself? In the form of ageing. Most interestingly is the time it takes for the telomeres to be entirely degraded. It's around 25 to 30 years, which around the same time ageing begins in the human body.

So there we are. Your DNA is like a shoelace, and the telomeres are like the aglets. When they are there, they keep everything in check.When they are removed, everything starts unravelling.

And then your shoe falls off. 

Tuesday, 10 January 2012

Why Do We Age?

Our medicines prevent many diseases from killing us. Advances in medical science have allowed us to fix damaged organs, like hearts, or in some cases replace them entirely. The further understanding of nutrition provides us with the knowledge we need to stay healthy throughout our lives. But despite all this, there is still no way to defy death permanently. We can prolong life, almost tripling its natural length, but eventually, the human body can no longer support itself.

So why does this happen? Whilst the precise cause of ageing is as of yet undetermined, there are many theories. One theory indicates that the mitochondria, which are the energy production units in our cells, cause damage to the cells over time via the release of harmful by-products. Mitochondria produce ATP (the energy currency of the cell) through several cycles that split glucose down into various compounds, releasing energy in the form of ATP along the way. This process can release electrons which form reactive oxygen species. You may be more familiar with these under the guise of free radicals. These molecules cause damage to several different components of the cell. Over time, this cell damage builds up, and we see the effects of this in the form of ageing.

Another theory is more centred around DNA as the cause of ageing. As you may know, DNA (or Deoxyribonucleic Acid to be precise) is found in every cell in our body and contains the instructions for each one of the cells. The DNA in our cells produce protein, which activate different functions around the body. When a cell divides, a copy of the DNA is made, after which the cell divides in two. The process of replication is balanced by the rate of cell death. In the first part of our lives, as we grow, the rate of cell division is higher than that of the rate of cell death. However, at about 25 years of age, the rate of cell division begins to decline. It is at this point where our bodies start "ageing" as we know it. This decline in division is the result of the degradation of telomeres. These little caps of DNA are fascinating, and I'll be taking a closer look at them in a future posts.

One final theory around ageing implicates insulin as a contributing factor. You probably already know of insulin through its role in diabetes, but studies have shown that it could also cause ageing when combined with a chemical referred to as insulin-like growth factor 1, or IGF-1. IGF-1 can bind to both specific receptors as well as insulin receptors. Many tests have been conducted on a variety of different species that indicate removal of insulin receptors can lead to incredible prolonging in life. An experiment showed that the lifespan of the roundworm species Caenorhabditis elegans could be doubled by mutating the gene that coded for the insulin-like receptor. Since the insulin/IGF-1 pathway is the same within both worms and mammals, this indicates a possible anti-ageing therapy that could extend life permanently.

It's difficult to say exactly if any of these are the one true cause of ageing. It could be that it is a combination of all the different theories, or it could be that one theory in turn stimulates the others. Whatever the case, each theory offers exciting avenues for potential therapies in anti-ageing.

An excellent review on insulin/IGF-1 ageing theories can be found here;

Monday, 2 January 2012

A Mission Statement

I feel that an introduction is necessary here.

My name is Eddie Johnston, and I am a biologist. At least, I am a student of biology. I'm in my third year of study at the University of Kent.

One of my favourite areas of biology, and to an extent science in general, is the science of immortality. It's incredible to see how in the last hundred or so years, we have dramatically increased life expectancy, by doubling and now almost tripling our natural life span.

Increasing our life span is a result of a combination of different factors. Better medicines prevent common disease from killing us. A better understanding of nutrition has improved our diets, making us healthier. Our society has changed, providing us with the food we need to survive at our convenience. We, as a species, have beaten nature at its own game.

But that's not the end of the battle. Regardless of how far we have stretched our lives out, humans eventually succumb to death. Whether it be through disease, accidents or simply old age, one way or the other life always comes to close. But recent scientific research is beginning to change that.

Over the coming weeks and months, I'm going to be looking at immortality science. Starting with the basic principles of ageing, I intend to go on to look at current research being done to prevent death through age, and finally look at where science may take us in the future. Along the way, I'll be taking time to look at the social and ethical implications brought on by the prospect of immortality.

So, let's get started.