Fibroblast Cells Physiological Changes

The senescent phenotype was first, and most thoroughly, described for those fibroblasts that reached replicative senescence. During the 1990s, several lines of evidence showed that cells sense the number of divisions they have completed by the length of their telomeres. Telomeres shorten with each round of DNA replication owing to the biochemistry of DNA synthesis, and the fact that most normal somatic cells, including fibroblasts, do not express the enzyme telomerase. Fibroblasts, and many other cell types, arrest growth with the senescent phenotype when they acquire one or more critically short telomere.

During the late 1990s, it became apparent that a number of stimuli other that short telomeres also induce fibroblasts and other cells to arrest growth with a senescent phenotype. These stimuli include certain levels and types of DNA damage and the expression of certain oncogenes. In addition, conditions or agents that decondense chromatin, which causes silenced genes to be expressed, induce a senescence response in normal human fibroblasts. These stimuli induce a senescence response independent of cell division and telomere shortening, and the process that leads to the senescent phenotype has thus been termed cellular senescence. Thus, replicative senescence is a special example of the more general process of cellular senescence. Short telomeres, DNA damage, oncogene expression, and loss of gene silencing have all been implicated in the initiation or promotion of cancer. For this and several other reasons, cellular senescence is thought to be important for suppressing tumorigenesis.