Thursday, November 3, 2011

100 year old cells were turned back into stem cells, and given new life

Rejuvenation of our cells and organs has been long sought after, in an attempt to make our bodies live longer. While we are not yet able to constantly revitalize ourselves, scientists have found a way to turn cells from people over a 100 years old back into primitive stem cells, which then acquired the ability of self-renewal, and the capacity to differentiate into many different cell types. While genetic reprogramming in order to transform ordinary cells in the body back to stem cells has been done many times before, French scientists have shown that age is no barrier for reprogramming, highlighting the possibility to squeeze much more life out of our cells than nature provides us.

For their reprogramming, the researchers used a cocktail of six genes. Four of those are often used to transform skin cells (fibroblasts) back into stem cells, to create so-called induced pluripotent stem cells (iPSC). The other two, Nanog and Lin28, were added to ensure that the reprogramming would work for cells that have been on the earth for over a century. Cells treated with the six factors showed that the iPSC had characteristics of embryonic stem cells, the most basic cells in our body. In the embryonic phase, they form all the cells required to make an adult body. It was only a short while ago that scientists succeeded in actually recreating embryonic stem cells, as opposed to iPSC, that have slightly less stem cell potential.

Interestingly, when the newly formed iPSC were re-differentiated to the cells they once were, all signs of cellular ageing were suddenly absent. This highlights that transformation to a stem cell phase completely reprograms the cell, basically giving it new life. It appears that cells which are well passed the senescent barrier were still usable in reprogramming experiments, which means there are no cellular barriers stopping them from being transformable into stem cells.

Normally, after cells reach a certain age, they are unable to proliferate any more. They turn into senescent cells. Why this happens is still being investigated, but one of the causes is shortening of our DNA. On the edge of our genome, we have a piece of genetic code that protect the edges of our chromosomes, the so-called telomeres. Each time our DNA is copied, the telomeres shorten, until after a certain point, they will be completely used up. After that, new rounds of DNA copying cause small pieces of the genome to break off, which eventually leads to enough damage to render cells dysfunctional, causing cells to stop dividing, commit suicide or cause cancer. Some cells, especially stem cells, have developed capabilities to restore the length of telomeres, which is supposedly one of the reasons stem cells are able to sustain themselves without signs of ageing. They posses an enzyme called telomerase, which functions in telomere elongation.
Overview showing telomere elongation.

This piece of research paves the way to cellular rejuvenation in elderly patients, that may suffer from disease or disabilities because their organs have reached old age. Clinical attempts to use reprogramming of cells could prove to be useful to extend the life of the elderly by solving all kinds of problems in the body: as long as we can reprogram and re-differentiate the required cells for repair. 

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