The Immortal Senescence

Abstract

Activation of oncogenic signaling paradoxically results in the permanent withdrawal from cell cycle and induction of senescence (oncogene-induced senescence (OIS)). OIS is a fail-safe mechanism used by the cells to prevent uncontrolled tumor-growth and, as such, it is considered as the first barrier against cancer. In order to progress, tumor cells thus need to first overcome the senescent phenotype. Despite the increasing attention gained by OIS in the past 20 years, this field is still rather young due to continuous emergence of novel pathways and processes involved in OIS. Among the many factors contributing to incomplete understanding of OIS are the lack of unequivocal markers for senescence and the complexity of the phenotypes revealed by senescent cells in in vivo and in vitro. OIS has been shown to play major roles at both the cellular and organismal levels in biological processes ranging from embryonic development to barrier to cancer progression. Here we will briefly outline major advances in methodologies that are being utilized for induction, identification and characterization of molecular processes in cells undergoing oncogene-induced senescence. The full description of such methodologies is provided in the corresponding chapters of the Book.

mTOR Activity and Autophagy in Senescent Cells, a Complex Partnership

“…As the exit from the cell cycle in senescent cells is commonly established and maintained through the activation of tumor suppressor pathways centered on p53 and/or pRb [ 28 ], it was rapidly recognized that cellular senescence represented a cell-intrinsic mechanism that limits the proliferation of damaged and potentially cancerous cells [ 4 ]. Thus, much like apoptosis, cellular senescence acts as a barrier that cells must overcome in order to become immortalized and transformed, explaining the high frequency at which these pathways become disrupted in human cancers [ 29 , 30 ].…”

JMJD3 in the regulation of human diseases

“…Aging is caused by a variety of mechanisms, including oncogenic signals, telomere shortening, and DNA damage. Induction of aging by oncogenes is one of the important mechanisms of aging (Bianchi-Smiraglia et al 2017). Epigenetic silencing of gene loci encoding aging pathway effectors usually occurs in normal dividing cells.…”

Sequential events during the quiescence to proliferation transition establish patterns of follicle cell differentiation in the Drosophila ovary

“…Alternatively, sif KD or sick KD FSCs may be rendered quiescent or senescent, unable to interpret feeding-dependent signals to enable normal FSC function. Given the propensity of oncogenes to initially induce senescence ( Bianchi-Smiraglia et al, 2017 ; Zhu et al, 2020 ) and the importance of quiescent states in cancer risk ( Paul et al, 2022 ), it may be of high interest to understand the phenotype observed in sif KD and sick KD FSCs as a mechanistic target to prevent transformation.…”