Immortality and Cancer

So what if we could just program our cells to be immortal?  after all, that little jellyfish I talked about earlier can manage it.  And they've managed to reverse aging in mice.  And if old age in cells leads to old age in people, then immortality in cells leads to...

Ah, be careful what you wish for.  There are already two kinds of immortal human cells I know of.  One is stem cells (and the jury is out on this, I believe).  Stem cells are cells that have not yet differentiated; have not yet found their purpose in life to see the world and be a retinal cell,  or perhaps help out a bit in the kidneys.  They are common in embryos.  Anyways, we're not here to talk about stem cells.

The other type of immortal cell is a cancer cell.  Cancer is a multifaceted disease of diabolical  sophistication, but all cancers rely on one thing:  a cell somewhere has being given the signal to perpetually divide. 

Most cells in your body don't reproduce, although all have the potential to.  Skin cells reproduce, as do red blood cells, and others.  But for the vast majority, part of the deal of living in a multicellular organism like people is ixnay on the cell division.

Normal human cells will divide about, I think, 50 times and then die of old age.  But not a cancer cell. They go on and on and on.

As a matter of fact one woman, let's call her Mrs. Tibbets, died of a particularly virulent form of cancer years ago.  Researchers were particularly interested in her cells, so they have kept her cell line going for decades in laboratories the world over.  In a way, you could say Mrs. Tibbets is still alive, as a 50 ton tumour dispersed throughout the globe.  Her DNA, albeit with a cancer mutation, is still alive in each of those cells.

So maybe this cell immortality ain't all it's cracked up to be. 

Cancer overcomes the "natural" aging limits on a cell, the genetic programming that leads to cell old age, or senescence.  A lot of things have to go wrong for you to get cancer.  First of all you have to get a mutation in your DNA which instructs the cell to just keep dividing over and over again.  Second of all, the cell's elaborate defence mechanisms that fix mutations or otherwise prevent rampant cell division have to be rendered inert.  And third of all, an obscure little enzyme called telomerase, active when you were an embryo and your cells were dividing like crazy, has to be manufactured by the cell again.  If I understand the theory correctly, anyway.

Telomers are little caps on the end of your chromosomes (DNA villages, if you will) that act as an internal clock for your cell.  Each time the cell divides a little bit is shaved off the cap, and when it is gone your chromosomes start sticking to everything and to each other, all hell breaks loose and the cell dies.  Telomerase creates more telomers, so that the cell can keep dividing without limit. 

A mutation may cause your cell to get, or to think that it is getting, growth signals to divide.  What is supposed to happen is that, when excessive or unscheduled cell reproduction is detected, tumour suppressing proteins like p53, the sentinel, shunt the cell to premature senescence and put a right stop to that.  But if something goes wrong with the gene that make p53 then that defence may be rendered ineffective.  And not just p53; in cancer a host of tumour suppressing genes must be stopped.  Even if the mutation is allowed to drive cell growth, there is still the cell clock—telomers—that will kill the cell after a certain amount of cell divisions.  Unless another mutation has instructed the cell, after all these years, to start manufacturing telomerase again.

Slim chance right?  Well, as stated last time, your average cell DNA probably gets hit by various things that can cause mutations tens of thousands of times a day.  You've got somewhere between ten and a hundred trillion cells.  Do the math.

So, having defeated this elaborate mechanism the cell is free to divide at will which it does.  It has become immortal.  Theoretically anyway.  In reality, of course, it winds up killing the host organism and dies with it.  (Except for Mrs. Tibbetts's tumour, which is still going strong.)

The interesting thing is that this p53 tumour-suppressing gene is believed to have a directing role in cell old age.  When p53 suspects something is wrong it pushes the cell towards old age, as a defence against out-of-control cell division.  From an evolutionary perspective, this is understandable—you don't want sub-standard cells dividing.  Just like old people, old cells have a hard time being active and reproducing.  Over time your DNA accumulate mutations—ones that may not necessarily cause cancer, but mutations nonetheless—and it's thought that perhaps these tumour-suppressing proteins like p53 initiate the old age program.  They prevent the cell from dividing, and perhaps (for cells that don't reproduce) from even from repairing itself properly.  So the cells don't work as well as they should and the overall affect on the body is old age.

From this point of view, aging itself can be seen as a defence mechanism against early cancer.  The tumour-suppression genes are great early on at preventing cancer.  Without them cancer would be very much more prevalent in younger people than it is.  But as the DNA accumulates random damage over time, the tumour-suppessing proteins detect this and institute the genetic senescence program.

Given that aging and cancer may be competing interests, it looks like my hopes of an immortality pill are slim.  I might get cellular immortality, but I'd be ripped apart by tumours soon after.

On the other hand, this is all theory.  Some researchers think that there are programmed "senescence effector" genes that actively initiate aging upon reproductive maturity.  Maybe it's just turning those cells off. 

As for immortality, dammit, if a jellyfish can do it, why can't I?


Incidentally, I should give a nod to William R. Clark's excellent text A Means to an End: The Biological Basis of Aging and Death, which was my primarily resource for this series.