Replicatieve celveroudering

Most animal cells divide a finite number of times before they stop and undergo permanent cell cycle arrest.

In a mitogenic medium, for example, human fibroblast cells divide about 25-50 times. As a cell approaches this finite number of divisions, the rate of cell division slows down and finally halts with cells entering a permanent non-dividing state. This phenomenon is called replicative cell senescence.

Replicative cell senescence is a result of changes in the structure of telomeres. Telomeres are located at the ends of the chromosomes and consist of long repetitive DNA sequences and protein complexes.

In the absence of telomeres, chromosome ends could be recognized as double-strand breaks. These ends could fuse to one another forming abnormal structures like a ring chromosome. The telomeres act as caps, protecting the ends of the chromosomes from degradation by nucleases and preventing the aberrant fusion of chromosome ends to one another.

Shelterin is a telomere-associated protein complex that protects the chromosome ends.

Shelterin helps DNA ends form a lariat-like structure called a telomerase-loop, or T-loop. This T-loop masks the DNA ends, preventing degradation.

During cel