Sunday, 25 March 2012

Telomerase: DNA DIY Delivery

So telomerase can fix up our telomere caps, which could theoretically rejuvenate our entire body, as well as maintain us at a young state forever. But the question is, how do we get the telomerase to the telomeres?

Unfortunately, this is not an option
Some scientists suggest the use of telomerase as a form of supplement, that could be taken when needed in order to maintain the telomere caps. This is one option, but the question remains of the form in which the telomerase might take in order for it to reach the cells in one piece.

A quick internet search for "telomerase drugs" gives you a stunning number of results for drugs that claim to slow, or in some cases completely reverse the telomere shortening process, such as this bottle of "Telomere Guard" which can be yours for only £56 pounds every five months.
I cannot stress enough how much of a con these things are. For a start, none of the results they claim on have actually been confirmed by any independent body. Anti-ageing medicines are currently classified as "cosmetics" meaning they require a much less strict screening policy. Secondly, they refer to the drug being able to "upregulate telomerase" without mentioning the potential cancer risks this brings. Basically, telomerase as a supplement might not be there just yet.

So no buying anything that claims
to be the fountain of youth

Having said that, a recent patent application describes a method of delivery for telomerase to cells via a "biodegradable nanoparticle", which as far as I can tell means a very, very small pill. This nanoparticle can be taken orally, or intravenously, or even topically (I think). Whilst this specific patent refers to using telomeres to tackle the ageing effects of Alzheimer's and other specific diseases, it shows that in the future, it may be possible to actually have an anti-ageing pill.

There is one last hope that would mean instead of taking a pill every day/week/year, your cells could just do it themselves. Gene therapy (or cell therapy) is a way of altering the DNA of your cells in order to change the way your body functions. It's not in wide spread use yet, but it presents potential cures for some of the most serious genetic diseases around, like cystic fibrosis, or Huntington's Disease.
As you might imagine it's not a particularly easy process, but by using a specially modified virus, it is possible to activate previously dormant sections of DNA in the cells. In the case of telomerase, people have suggested activating the genes in our cells that produce telomerase so that they simple produce more of the stuff, keeping our telomeres extended for longer.

There is always the concerns of cancer when talking of using telomeres, but there is actually a model of this in the animal kingdom already. It turns out lobsters have an incredibly high concentration of telomerase in their bodies, which means that they can hypothetically live forever. Just imagine. At the bottom of the ocean, there could be lobsters the size of buses.

So, telomerase it does the job well enough, it's just a matter of getting it to the cells. Whilst the "telomerase pill" might not be available yet (no matter what the snake oil salesmen might tell you) it may one day become a reality. There's also the option of getting our cells to produce the stuff, which would provide us with all the telomerase we need.

We have to be careful though. Don't want to end up with a bunch of mutant lobster-men on our hands.

Case in point

Thursday, 22 March 2012

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;

Monday, 19 March 2012

Telomerase: DNA DIY

Before we get start, why not take a quick look back at my initial blog post explaining how telomeres work, and how they cause the effects of ageing. I'll be ready to go when you get back.

So, our telomeres have been worn away by constant division of cells, to the point where the DNA is being damaged. So it would seem the simplest option would be to some how repair the telomeres.

Enter telomerase.

Okay, these structural images aren't quite as dramatic as I'd like

Telomerase is an enzyme which has the incredibly useful function of restoring and rebuilding the telomere caps on the ends of the DNA. It does this by binding to the DNA, and adding on the appropriate bases that form the telomere. This is illustrated clearly in the image below;

As you can see, the telomerase contains an "RNA template", which binds the bases (or to give them their proper title, nucleotides). The result of this? The telomeres are restored back to their former glory.

To take it back to my original shoelace metaphor, telomerase would be like repairing the aglets on your shoelace with sellotape. Okay, that's not a perfect metaphor, but you understand what I'm saying. Telomerase repairs and restore the telomeres.

As you might imagine, there have already been a wealth of studies into the different effects of telomerase, and how we might be able to utilise these effects in life-extension therapies. I'll be looking more at these next time. See you then.

Wednesday, 14 March 2012

Presentation and Correct

Apologies for the lack of updates recently, but as will soon become apparent, my scientific focus has been elsewhere for the past week or so.

As part of my final year project, I put together a presentation based on the ideas and theories behind my blog. You can watch the video right here.

The presentation goes a little ahead of what I've covered so far in the blog, so over the next few weeks I'll be looking more into life extension therapies, as well as covering the ethics in great detail. I hope you can join me.