People are living longer, healthier lives in spite of the inevitable aging process that haunts us all. Cancer cells don’t age and we’re starting to understand why. Unfortunately, the same mechanisms that keep cancer cells immortal are those that make them so dangerous... Research has shown that in the future we may be able to take control of this process, but can we learn to harness it for our own use?
(Credit: Flickr/KimCarpenter NJ)
Have you ever wondered what it would be like to live forever? Recent advances in our knowledge of biochemical pathways have demonstrated that we’ve already made good progress towards living a great deal longer and that it may not be as far-fetched as we think. Sometimes, though, living forever doescome at a rather large price: when our cells achieve immortality, the result is what we know as cancer.
The aging process is a precursor to death and thereby an indicator of our mortality. A signal telling us that yes – we must die. This process, a progressive breakdown of our organism, remains independent of disease. Aging is different to disease, even though our lifestyle can influence it; aging is a natural biological process that we see in all life.
More people are living longer than ever before
While immortality remains a little out of our grasp, we ever-resourceful human beings have managed to more than double our life expectancy in the past few centuries with only relatively slight modifications to our lifestyle. This increase is largely thanks to advances in medical treatment, vaccination, nutrition, sanitation, democracy and simply having greater control over the potential hazards in life. Yet even these lifestyle enhancements cannot seem to push the oldest of the old to live significantly longer. Rather, the result seems to be that more of us are increasingly aware of the effects of aging, whereas in times gone by few people lived long enough to observe them. This includes, of course, the usual grey hair and wrinkles, but also increasing risk of certain medical conditions—in particular, age-related illnesses such as osteoporosis, Alzheimer’s and Parkinson’s diseases, or cancer and heart disease—which we currently have no easy ways to cure.
The life expectancy, based on the average lifespan of a species, is not to be confused with maximum lifespan, the age of the oldest living individual of a species. Currently, the oldest recorded person died at 122 years old – a female, as with 9/10 of the “top survivors”. Ladies tend to live just a touch longer than men, for several reasons related to gender differences, some of which are still under debate.
The maximum lifespan appears to be a biological limit, which we are struggling to push any further. Nonetheless, in these modern times we have become very good at fighting some of the exterior signs of aging: tucking in and lifting up the effects of a lifetime of gravity, colouring or even replacing lost hair, and so forth. Unfortunately these methods are simply a game of smoke and mirrors, as we now know that aging is an extremely complex biological process that cuts right down to the cellular level.
Cancer cells vs. Aging cells
Aging at the cellular level, known as cellular senescence, is the stage where a cell steps out of the cycle of cell division. It therefore stops dividing (reproducing) and will “age” until it dies. Thus, all cells have a predetermined aging process destined to be switched on once the cell has passed its “sell-by date” – normally after 50 to 70 divisions. It’s almost as if the cell comes programmedwith a maximum lifespan.
Cancer cells, however, are immortal; they do not die. Why they don’t die is a very complicated issue to resolve. But one thing we do know is that cancer cells don’t show the usual signs of aging. They lose the capacity to make the switch to “senescence-mode”, rendering them immortal – which, at first glance, might seem supernatural (move over Twilight cast!). But, sorry to say, it is not at all a good thing, as the internal cellular motor keeps running non-stop, out of control. Those cells, unable to make that switch to “I’m old now”, don’t die. They just keep reproducing over and over and over again, giving rise to one big, disordered mass of cells - a tumour.
So what controls all this stuff? Both senescence and cancer can be instigated by our genes, the long sequences of DNA that basically tell every cell in our bodies what to do. But don’t be fooled, as sometimes our DNA gets it wrong – like a computer that won’t stop freezing up I know, it’s annoying when that happens, right? Even worse, there’s often no *Ctrl-Alt-Del* function in biology.
The DNA found in a human cell is around 6 billion base pairs long and contains roughly 25,000 genes. It is estimated that the number of bits of damaged DNA in any given cell is somewhere between 1,000 and 1,000,000 per day. At most, that’s less than 1/5,000 of the entire genome. Not so dangerous you might think - unless those damaging mutations occur in a region of DNA required to fight tumours or activate senescence and can’t be treated by the cell’s internal DNA-repair enzymes. One shock to the system in the wrong place and the cell can become incapable of initiating senescence.
We do, however, have some protection on our side. There are several important genes controlling the switch between mortality and immortality, including P53 and P16, which trigger senescence in cells containing potentially cancerous mutations. However, if these cancer-protective genes are damaged or mutated, the cell loses these defence mechanisms and becomes cancerously immortal.
Cancer cells have other methods of avoiding the aging process. As we’ve already mentioned, the sequence of bases is fragile and susceptible to damage from outside sources. Similarly, every time a cell divides, a small fragment at the end of each chromosome is lost. In order to counteract this effect, telomeres – long repeating sequences of genetic code – are attached to the end of chromosomes. It is these telomeres that are lost little by little with each cell division, instead of the potentially useful gene-containing DNA sequences. When they are cut too short, the cell becomes senescent, thus signalling aging and death – cell mortality.
Although telomere shortening and cell aging occur at the same time, we don’t yet know if it actually switches on the cellular aging process. But, remarkably, cancer cells are somehow able to turn on the enzyme telomerase, which rebuilds these telomeres as the cell divides, preventing it from detecting when it has become too old, blocking the senescence switch and maintaining its immortal status.
The genetic and telomeric signals that guarantee the activation of the aging process in cells are the same signals that help keep cellular growth under control. Scientists are currently looking into targeting the P53 and P16 genes, the telomerase enzyme or other ways to switch on cellular senescence to help fight our ongoing battle against cancer. This means that, paradoxically, it is those very aspects rendering us mere mortals that could be used to oppose our immortal enemy.
Even considering everything we already know about cellular aging and cancer, these concepts are still a way off from being put into practise at the whole-body scale. Nevertheless, simple changes have made big differences where lifespan is concerned; the proof can be found in any retirement home near you. Perhaps one day we will even be capable of harnessing the power of cancer to attain immortality or inversely govern the strength of mortality to defeat cancer. For the time being, however, we can’t have either – that’s the Immortality Catch-22.
About the author:
Originally from Leeds (UK), James Bowers, is studying for his PhD in Biology specialising in aging, at the National Museum of Natural History, France. A graduate of Medial Biochemistry from the University of Manchester, James is now funded by an EU Marie-Curie scheme, allowing him to relocate to Paris in 2010 to work under the supervision of Prof. Demeneix and Dr. Clerget-Froidevaux.