Reseting the Human Cell Clock

   In the June 2010 issue of Life Extension magazine is an interview with Michael West, PhD, CEO of BioTime inc.  Dr. West claims that his company is taking human body cells, (somatic cells) and restoring them to an undifferentiated state (like a stem cell) and also restoring them to a youthful age.  These cells are called iPS cells (induced pluripotent stem.)   BioTime is using a patented proprietary technology called ReCyte to accomplish this transformation.  They use genes (transcription factors) that are normally active only in reproductive cells.  ReCyte uses genetically engineered testicular cells to express large quantities of Oct4, Sox2, and Lin28 to transform a patient’s body cell back to an earlier state.  

            When perfected, such a technique could supply large quantities of “patient specific” youthful, undifferentiated cells which, if introduced into a damaged organ could make whatever repairs are required, taking their instructions from the surrounding tissue and essentially rebuilding the organ. 

            The transformation of old somatic cells into undifferentiated young stem cells has been accomplished before, using cloning.  If an adult body cell nucleus is introduced into an egg cell that has had its nucleus removed, the resulting cell can be tricked into thinking it’s a fertilized egg cell and begin dividing—and producing stem cells.  And such cells are both undifferentiated and youthful—but not always with enough telomere length to be “totally youthful.”               

            Every chromosome has strands of DNA on each end called telomeres that function as a cell clock. Each time the cell divides, the telomeres shorten.  After some finite number of divisions, the telomeres are too short—and the cell will no longer divide.  But the reproductive cells have the ability to re-divide indefinitely with no change in telomere length. Yet as an embryo develops past a certain stage and tissue begins to differentiate, then each additional division causes telomere shortening.  And that’s what limits life span.  Cells continually die or are damaged, but each cell can regenerate itself only a set number of times.  When cell replacement fails to keep pace with cell damage and death, we call this aging.  But this limitation, though natural, is still artificial.  Some species of animals can regenerate entire lost organs.  At some point in our evolutionary past we too must have had this kind of ability, but it’s been turned off.  We are now looking for the switch to turn it back on.

            DEATH AS A RECENT INVENTION

       In one of the sidebars of this article, is an interesting philosophical reflection.  Death only dates back to the development of multi-celled life.  But for most of the time life has existed on Earth, all life was mono-cellular, and death was not required.  An individual cell might be eaten by some other organism, but it might also divide and reproduce, and keep doing so indefinitely.  Death was a possibility, but not a destiny.  And all cells were reproductive cells.  But somewhere these sex cells evolved the ability to grow “helper cells,”  additional cells to help in the main function of reproduction—by finding food—fending off predators, or whatever.   So what happens to these ancillary systems once the primary goal of reproduction has been accomplished?  Having fulfilled their function, they are cast off to die.  By now reproduction had become sexual, and the sex cells themselves do not all die—some become part of the next generation.   And of course, the sex cells have to survive—as they contain the genes.  But today, the rest of the organism, this “life support for a bunch of DNA,” has evolved a brain and a conscious sense of self—and we’d prefer not to die—at least, not just yet.  So, in the greatest of ironies,  these brains now search for the code to immortality in the one part of the body which still has it—the sex cells.