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The phosphorylation cascade initiated by these two kinases causes the eventual arrest of the cell cycle. Depending on the severity of the DNA damage, the cells may no longer be able to undergo repair and either go through apoptosis or cell senescence. [8] Such senescent cells in mammalian culture and tissues retain DSBs and DDR markers. [14]
The typical normal human fetal cell will divide between 50 and 70 times before experiencing senescence. As the cell divides, the telomeres on the ends of chromosomes shorten. The Hayflick limit is the limit on cell replication imposed by the shortening of telomeres with each division. This end stage is known as cellular senescence.
A cell that has accumulated a large amount of DNA damage or can no longer effectively repair its DNA may enter one of three possible states: an irreversible state of dormancy, known as senescence; cell suicide, also known as apoptosis or programmed cell death; unregulated cell division, which can lead to the formation of a tumor that is cancerous
Senescence-associated beta-galactosidase, along with p16 Ink4A, is regarded to be a biomarker of cellular senescence. [ 1 ] [ 2 ] Its existence was proposed in 1995 by Dimri et al. [ 3 ] following the observation that when beta-galactosidase assays were carried out at pH 6.0, only cells in senescence state develop staining.
Programmed cell death (PCD; sometimes referred to as cellular suicide [1]) is the death of a cell as a result of events inside of a cell, such as apoptosis or autophagy. [ 2 ] [ 3 ] PCD is carried out in a biological process , which usually confers advantage during an organism's lifecycle .
Chromatin architectural remodeling is implicated in the process of cellular senescence, which is related to, and yet distinct from, organismal aging. Replicative cellular senescence refers to a permanent cell cycle arrest where post-mitotic cells continue to exist as metabolically active cells but fail to proliferate.
The term "immortalization" was first applied to cancer cells that expressed the telomere-lengthening enzyme telomerase, and thereby avoided apoptosis—i.e. cell death caused by intracellular mechanisms. Among the most commonly used cell lines are HeLa and Jurkat, both of which are immortalized cancer cell lines. [4]
Apoptosis is the programmed cell death of superfluous or potentially harmful cells in the body. It is an energy-dependent process mediated by proteolytic enzymes called caspases, which trigger cell death through the cleaving of specific proteins in the cytoplasm and nucleus. [ 13 ]