Cellular Senescence as a Target in Cancer Control

Table 1

Cellular clock driving senescence hypothesis.

Cellular clock	Cause	Molecular readout
Error-catastrophe theories
Somatic mutation accumulation	Metabolism/oxygen free radicals	Altered protein function, DNA damage
Mitochondrial DNA mutation	Oxygen free radicals	Altered mitochondrial function
Posttranslational modification of proteins	Oxidation, glycosylation, acetylation, methylation, and so forth	Altered function of proteins
Altered proteolysis	Errors in proteolysis machinery	Accumulation non functional proteins
Deterministic theories
Telomere shortening	no replication of the telomere ends	DNA damage, exposure ends of telomeres, Liberation regulatory proteins, and so forth
Changes in heterochromatin domains		changes in transcription
Changes in DNA methylation		changes in transcription
Codon restriction	Switching codon preferences in early development, restrict availability later In life	Altered protein synthesis
Terminal differentiation	Senescence is a form of terminal di- fferentiation genetically controlled

Several hypotheses for cellular clocks driving senescence have been proposed. Most of them lay into error-catastrophe theories, suggesting that senescence is a byproduct of cell living, and deterministic theories, suggesting a genetic program for cellular senescence. Some of the most representative theories are collected in this table.