A Slight SENS of Deja Vu...

Have you heard of Aubrey de Grey? You might have seen him on TV at some point speaking on the topic of life extension.


He also has a beard which suggests he
is very serious about living forever.

 de Grey is the author of SENS, or "Strategies for Engineered Negligible Senescence". Put more clearly, it's a collection of therapies that tackle a variety of different elements of the ageing process. Let's take a look.

Cancerous mutations

Problem: In SENS, the only mutations that matter are the ones that cause you cancer. Other non-cancerous mutations may still occur, but are made redudant by the vast number of other cells around them. Cancer is an ageing related disease and one of the reasons the chance of dying increases as we grow old, according to this theory.

Solution: Cure cancer. It sounds obvious, but unfortunately, it's the only real way to avoid this problem. Cancer therapies are improving all the time, so it's not quite as sci-fi as it first appears. SENS specifically focuses in on your friend and mine, telomeres, in order to tackle the cancer problem.

Mitochondrial mutations

Problem: Mitochondrial DNA mutates. This causes damage to the energy production of the cell, possibly through the release of certain harmful products. de Gray himself has actually gone back on this theory, stating that the number of mutations observed in mitochondrial DNA (about one every 7884 years) probably isn't enough to account for ageing.

Solution: Something called allotopic expression, which would involve moving the mitochondrial DNA further into the cell in order to protect it.

Intracellular Junk

Problem: Over time, byproducts produced by the cell can build up and cause ageing effects. Alzheimer's disease, retinal deteriation and even liver spots are all caused by this build up of "junk"

Solution: The cell has a collection of miniature organs within it called lysosomes which function to digest unwanted molecules and byproducts. de Grey suggests adding new enzymes to the lysosomes, specifically ones from molds and bacteria that display efficient and complete digestion, in order to reduce the build up of waste products.

Extracellular Junk

Problem: The same as before, but this time, outside of the cell. This can often be toxins, or other damaging substances.

Solution: Use phagocytes to clear the junk up. Phagocytes are essentially eating cells. They are actually used by the body to swarm areas of infection and absorb and digest infectious organism, but they could easily turn their hand to toxin clean up.

Cell Loss

Problem: Whilst the majority of cells keep in a good balance of death and growth, some cells divide much slower, specifically those in the brain, heart and certain muscle tissues. As a result, over time these tissues grow weaker and cannot function properly.

Solution: Stem cells. The magical cells that can become any kind of cells around them (within reason) would be perfect for replacing cells lost over time.

Cell Senesence

Problem: This is where cells stop dividing, but don't die. This prevents other cells from dividing and causes damage to tissue over time.


Solution: Controlled cell demolition, sort of. By introducing specific genes, inventively called suicide genes, cells can be instructed to self destruct and stop blocking the replication of other healthy cells.

Extracellular Crosslinks

Problem: Cells in the body are held together by special link proteins. If too many of these cross links form between cells in a tissue, it can actually cause the tissue problems. In some cases, the high amount of bonds can cause the tissue to become brittle, weak and easier to damage.

Solution: The use of small molecule drugs and ezymes to severe the sugar cross links between the cells and tissues in order to keep them healthy.

As you can see, there are a wide number of different elements of aging covered in the SENS approach. You'll have probably noticed that some of topics I've mentioned bear quite a lot of resemblance to some of the other theories of ageing I've previously mentioned.

The idea behind SENS however, is not just to show how ageing works, but to provide an united front approach to life extension therapy. SENS gathers together all of the leading theories and works them into something of a therapy checklist; a strong approach that tackles a wide number of causes of aging.

It's not without its criticisms however. Some suggest that SENS is nothing but a science fiction wondering, and is too complex to be implemented anytime in the near future. Whilst many areas of research are undoubtable beneficial, such as cancer therapies, or stem cell research, critics claim that other areas, like alloptopic expression or crosslink destruction, are irrelevant and fanciful.

If you would like to disover more about SENS, the official website contains a large amount of indepth information.

I will finish with a video showing a TED talk that Aubrey de Grey gave back in 2006 on the topic of life extension;

...And Another Thing: Other Theories of Ageing

We've almost reached the end of looking at theories of ageing, but before we move on to how we might be able to stop these effects, I thought we might stop and take a closer look at a few more theories of ageing I haven't mentioned. So let's have a look at what we have.

The Evolutionary Theory of Ageing


The evolutionary approach suggests that the reason for ageing, and subsequent death, is, simply put, a cost saving measure. As an organism spends more time alive, there is a higher chance of something external (like disease or physical accident) killing it. Eventually something will kill the organism. In terms of resources, it's actually futile for the body to continue maintaining itself after it has reproduced. Enter ageing. After passing the point in its life where it is most fertile and completed its responsibility of child rearing (which in humans is around thirty, which oddly enough is when we start to age), an organism will start to age through processes triggered by its own genes.

Like the majority of theories related to evolution, it's all about survival. We only begin to age once we can no longer breed. Once we have created offspring, our usefulness is outlived. Thusly, our bodies start to die, so to not waste resources staving off the inevitable for a few years. It's harsh but morbidly utilitarian.

Why won't I be talking more about this theory? Well for one, it's more of an overarching theory on "Why we age?" as opposed to "How we age?". A lot of the other theories of aging that I have previously talked about could actually be the "how" to the "why" of the evolutionary theory. As interesting as the evolutionary theory might be, it doesn't present an awful lot of avenues to becoming immortal.

Autoimmunity and Ageing

As its name might suggest, the autoimmune theory of ageing suggests that the mistakes of our own immune system cause damage to our bodies over time. The term "autoimmunity" refers to our immune system, which includes our white blood cells, attacking the cells of our body for a variety of reasons. Normally, immune cells that are autoimmune would be destroyed by the body when they were intially produced. However, some of these cells might escape destruction and go on to cause damage to tissues around the body.

The theory indicates that autoimmune damage to specific tissue, such as the thyroid gland, might be responsible for the effects of ageing. The thyroid produces a large number of hormones responsible for growth and maintence of the body. If the thyroid were to be damaged by autoimmune action, the production of these hormones could be interuppted. The idea is that, over time, the increase in autoimmune cells and damage to the thyroid and other tissues results in the body no longer producing the correct hormones to keep us alive. As a result, the body starts breaking down, so on and so forth. AGEING.

The trouble with this theory is the whole "cause or symptom" dilemma which turns up far too often in biology. Whilst some maintain that the increase in autoimmune cells is a result of build-up over time, others suggest that the increased production is the result of another theory of ageing, such as the telomeres theory, or the mitochondrial theory. Some even suggest that the autoimmunity seen in elderly patients is infact just an oppotunistic disease that takes advantage of aged patients. Because of this, it feels ineffectual to attack autoimmunity as the cause of ageing, but better to aim straight for the cause.

Accumulative Waste Theory

The cells are often compared to tiny factories within the body, and that's a pretty apt description. There's a hundred different metabolic cycles all producing a plethora of different substances (and I should know, I've spent the last three years learning about them). Unlucky for us, then, that these processes often result in the production of unwanted chemicals, which tend to be toxic. Under normal circumstance, the body is rid of these byproducts through yet more metabolic cycles. However, the cycles aren't perfect and some of these waste products can be left over. Over time, these products can build up and cause damage to the body tissues. What does that sound like? AGEING!

You might notice a similarity between this theory and the mitochrondrial theory, by which I mean this theory basically IS the mitochrondrial theory of ageing, but with the words "reactive oxygen species" replaced with "toxic substances", and "mitochondria" with "cells" Essentially, the accumulative waste theory is a sort of more general mitchondrial theory of ageing, accusing the cell, and by extension, organs, of producing harmful waste products.

So here we are then. We've taken a look at a variety of theories of ageing, explore how and why they function in the way the do. All that's left to do now is try to stop that from happening, which is what I will be talking about next time.

So get ready for several months of bad "elixir of life" jokes

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.

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; http://www.fly-bay.net/journals/cc/BartkeCC7-21.pdf