Hayflick (un)limit(ed)

 

Time and tide wait for no man ~ Unknown

In 1961 Dr Leonard Hayflick demonstrated that a population of normal human fetal cells in a cell culture divide between 40 and 60 times. After this it then enters a senescence phase. Cellular senescence is a state where the cell is unable to replicate itself (mitotic division), so it either dies due to un-repairable damage or pre-empting this, because it may negatively affect the organism (You), commits suicide (apotosis) to ensure the organisms survival. Since we are all made of cells, this is fairly pertinent to every single one of us.

How this occurs is that with each mitotic division, a segment on the end of the DNA of the cell called a Telomere shortens. Telomere shortening in humans eventually makes cell division impossible, it is this shortened state that correlates with ageing.

This point of no return was coined the Hayflick limit and suggested a sort of in-built clock of ageing. As always, the devil is in the details, we just have to be smart enough to notice them.

Astute readers would have noticed that the studies used cells in a culture medium. At the time of the study they were using a culture medium that Hayflick and his colleagues thought provided all of the nutrients needed to support a human cell. Not so. They were missing some quite pivotal cast members. I won’t get into which nutrients were missing, we can do that at another time. The point is, by not having the appropriate nutrients present, the functioning of the cell altered so that it was less resilient to the stresses of life, even if that life consisted of living in a petri dish.

However, despite this, Hayflick did show us the mechanism behind ageing. Armed with that information, very smart scientists looked at the routes in which telomeres shorten. It doesn’t just happen in one way, as the saying goes ‘there are many paths to the top of the mountain’. I will show you the main paths in subsequent articles, but if you have being following my recent writing you will notice a trend towards the topic of stress and stress management. I did this for a reason, as current evidence has shown that the two (Stress and Telomere Shortening) are inextricably linked. We will look at this in the next article, but first of all we need to give ourselves a firm grasp of the basic mechanism.

So the question is, what are telomeres, and why is their length so important? Well, the DNA in your body is in the form of a double helix, essentially a two piece plat, like you would do to your hair, or similar to a shoelace. At the end of the plat, to prevent it becoming untangled, a hair-band is usually used. On a shoelace, again to prevent unravelling, we have a cap known as an ‘aiglet’. At the ends of our strands of DNA we have telomeres, whose main function is to prevent chromosome breaks and fusing. This operation helps to promote the genomic stability that we had a cursory glance at in the last article in this series.

Telomeres are non-coding repeating sections of DNA (about 9.000-15,000 repeats of the codons TTAGGG, then finally around 50-300 single repeats of (G)uanine, for those that are interested). As I suggested above, upon each cell division, your telomeres tend to shorten, until they reach a critical length where this informs the cell to cease replication and die off. The shortening occurs because an enzyme called DNA polymerase cannot completely replicate the entire DNA strand, so a little piece is left off each time. Luckily, as mentioned, this part doesn’t code for anything in the body, so you don’t suddenly lose huge chunks of DNA every time a cell divides. There’s method in the seeming madness.

So, since the body is made of systems and systems are a complex array of interplaying tissues, which are made of cells, when too many tissue cells die, organs fail, and generally so do you.  So does this mean that Hayflick was right afterall? Nope. Nature is a savvy mistress, and endowed us, the more fit (in evolutionary terms), to continue to play on this mortal coil, but only if we play by her rules.

Before we look at the rules, let’s look at how Nature helps us avoid the above scenario? Looking at the above situation, it seems that there is an inescapable freefall of bodily function until death. However, even a freefall can be controlled; much like a glider does in the air. Gliding’s good, especially when you’re hurtling, to your death, but we can go one better. What’s better? Let’s add some engines to our glider, so that we can dictate our rate of descent or even ascent. That way, if we hit the right control buttons, we can go as far and wide as we please.      

This engine is called Telomerase. Telomerase is an enzyme that functions in a number of ways, but the one we are most interested in is its effects on Telomere length. Telomerase has the ability to slow the rate of telomere shortening. Even better, it can maintain the length of telomeres. Best of all, it can actually lengthen the telomere. That’s right, you can literally wind back the hands on the clock of aging.

So to prevent ageing, we need to look after our telomeres and attempt to inhibit the processes that cause them to shorten. In addition to this we need to stimulate an increase in the activity and amount of telomerase, to protect and help us re-lengthen already shortened telomeres.

The research into telomeres whilst not new in the sense of our fast paced world, is still embryonic in all actuality. The initial idea was first suggested in the early 1970’s, and it wasn’t until 1978 that actual evidence of their existence was published. It’s only recently with advanced technology that we have been able to start accurately researching this area. But the scientists have been busy and there is a rapidly growing pile of research into this fascinating process.

In the next article, I’ll bring you up to speed about the main known causes of telomere shortening and ways to combat these factors. We’ll also look at the current science in telomerase activation.