Functional heterogeneity in senescence

Senescence is a tumour suppressor mechanism which is cell-intrinsically activated in the context of cellular stress. Senescence can further be propagated to neighbouring cells, a process called secondary senescence induction. Secondary senescence was initially shown as a paracrine response to the se...

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Bibliographic Details
Published in:Biochemical Society transactions Vol. 48; no. 3; p. 765
Main Authors: Kirschner, Kristina, Rattanavirotkul, Nattaphong, Quince, Megan F, Chandra, Tamir
Format: Journal Article
Language:English
Published: England 30.06.2020
Subjects:
Animals
Cellular Senescence
Cytokines - metabolism
Diploidy
Fibroblasts - metabolism
Fibrosis
Humans
Insulin-Secreting Cells - metabolism
Kidney - cytology
Mice
Pancreas - cytology
Phenotype
Receptors, Notch - metabolism
Signal Transduction
Skin - cytology
Wound Healing
senescence
senotherapy
secondary senescence
heterogeneity
Notch
ISSN:1470-8752, 1470-8752
Online Access:Get more information
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Summary:Senescence is a tumour suppressor mechanism which is cell-intrinsically activated in the context of cellular stress. Senescence can further be propagated to neighbouring cells, a process called secondary senescence induction. Secondary senescence was initially shown as a paracrine response to the secretion of cytokines from primary senescent cells. More recently, juxtacrine Notch signalling has been implicated in mediating secondary senescence induction. Primary and secondary senescent induction results in distinct transcriptional outcomes. In addition, cell type and the stimulus in which senescence is induced can lead to variations in the phenotype of the senescence response. It is unclear whether heterogeneous senescent end-points are associated with distinct cellular function in situ, presenting functional heterogeneity. Thus, understanding senescence heterogeneity could prove to be important when devising ways of targeting senescent cells by senolytics, senostatics or senogenics. In this review, we discuss a role for functional heterogeneity in senescence in tissue- and cell-type specific manners, highlighting potential differences in senescence outcomes of primary and secondary senescence.
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ISSN:1470-8752
1470-8752
DOI:10.1042/BST20190109