Senescence is a robust tumor suppressive mechanism that inhibits the proliferation of damaged as well as initiated cells in response to a diverse range of stresses. The observations that human benign cancer precursor lesions are comprised of senescent cells further provide evidence that senescence is a physiological mechanism that prevents cancer progression in humans, possibly at an early stage. Senescence is clearly not fail-safe, since cells in pre-cursor lesions occasionally progress towards advance stages of cancer (Michaloglou et al., 2005). However, what remains unclear is if cells in these pre-cursor lesions escape senescence by acquiring changes that help them overcome the restrictive barriers of proliferation or if cancer progression
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Classically, senescence is broadly categorized into two types 1) Replicative senescence and 2) Stress induced premature senescence (SIPS). Replicative senescence is induced in cells due to shortening of telomeres as a result of prolonged cell proliferation (discussed later), while premature senescence is induced in cells in response to cell intrinsic as well as extrinsic stresses such as oncogene activation, UV irradiation, DNA damaging agents, inadequate cell culture conditions, reactive oxygen species (ROS) amongst others. Although premature senescence induced in response to stresses was initially thought to be telomere independent, there is now evidence that demonstrates that premature senescence in response to certain stresses such as oxidative stress and oncogene activation is also stabilized due to the accumulation of dysfunctional telomeres (Suram et al., 2012; von Zglinicki, 2002). Therefore, we re-categorize senescence into 1) telomere associated senescence that occur in cells due to gradual or abrupt accumulation of dysfunctional telomeres and 2) Telomere independent senescence that is primarily mediated by activation of p16 and is also known as stress induced premature senescence
Classically, senescence is broadly categorized into two types 1) Replicative senescence and 2) Stress induced premature senescence (SIPS). Replicative senescence is induced in cells due to shortening of telomeres as a result of prolonged cell proliferation (discussed later), while premature senescence is induced in cells in response to cell intrinsic as well as extrinsic stresses such as oncogene activation, UV irradiation, DNA damaging agents, inadequate cell culture conditions, reactive oxygen species (ROS) amongst others. Although premature senescence induced in response to stresses was initially thought to be telomere independent, there is now evidence that demonstrates that premature senescence in response to certain stresses such as oxidative stress and oncogene activation is also stabilized due to the accumulation of dysfunctional telomeres (Suram et al., 2012; von Zglinicki, 2002). Therefore, we re-categorize senescence into 1) telomere associated senescence that occur in cells due to gradual or abrupt accumulation of dysfunctional telomeres and 2) Telomere independent senescence that is primarily mediated by activation of p16 and is also known as stress induced premature senescence