In 2009, Elizabeth. H. Blackburn, Carol W. Greider and Jack W. Szostak were awarded the Nobel Prize in Physiology or Medicine for their discovery of telomerase, an enzyme that replenishes the telomeres (see figure 1), DNA sequences at the endings of the chromosomes which appear to play a very important role in the aging process. This process, however, is far from being completely elucidated.
Figure 1: Human chromosomes, with the telomeres highlighted. (Source: National Institute of General Medical Sciences)
A new study seems to provide another step forward in our understanding. Researchers from the National Institutes of Health have identified a link between the previously mentioned telomeres and a toxic protein called progerin, which is associated with several symptoms of cellular aging. It turns out that, as the telomeres shorten (which happens during subsequent cell divisions), the production of progerin rises. Since progerin is a mutated version of a normal protein that goes by the name lamin A, which plays a large part in maintaining the normal structure of a cell’s nucleus, excess progerin is bad news.
Now, how are telomeres and progerin linked? It turns out that, as telomeres shorten, RNA splicing is affected. RNA splicing is an important step in turning a DNA sequence into a protein. During this process, introns are removed and exons are ‘pasted’ together (see figure 2). This splicing mechanism seems to be influenced by the shortening telomeres, leading to ‘bad versions’ of lamin A, also known as progerin. This was found through laboratory experiments with ‘immortalized’ cells (made that way by adding telomerase), which were found to produce very little progerin.
Figure 2: RNA splicing. (Source: Panda's Thumb)
So, as cells go through their divisions, their telomeres shorten. This, in turn affects the RNA splicing process, resulting in the malformation of several proteins, most notably so far, lamin A, responsible for the structural integrity of the cell’s nucleus.
Cao, K.; Blair, C.D.; Faddah, D.A.; Kieckhaefer, J.E.; Olive, M.; Erdos, M.R.; Nabel, E.G. and Collins, F.R. (2011). Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts. The Journal of Clinical Investigation. doi: 10.1172/JCI43578. (Click here for the article.)