Functional heterogeneity in senescence

Kirschner, K. , Rattanavirotkul, N., Quince, M. F. and Chandra, T. (2020) Functional heterogeneity in senescence. Biochemical Society Transactions, 48(3), pp. 765-773. (doi: 10.1042/BST20190109) (PMID:32369550) (PMCID:PMC7329341)

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Abstract

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.

Item Type:Articles
Additional Information:M.Q. is funded by the University of Glasgow MVLS DTP Ph.D. studentship. K.K. is funded by a John Goldman Fellowship sponsored by the Leukaemia U.K. (2019/JGT/003). N.R. was supported by a Ph.D. studentship funded by the Wellcome Trust Sanger Institute (206194) and the Royal Thai Government. T.C. is supported by a Chancellor’s Fellowship held at the University of Edinburgh.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kirschner, Dr Kristina and Quince, Megan
Authors: Kirschner, K., Rattanavirotkul, N., Quince, M. F., and Chandra, T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Biochemical Society Transactions
Publisher:Portland Press
ISSN:0300-5127
ISSN (Online):1470-8752
Published Online:05 May 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Biochemical Society Transactions 48(3): 765-773
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
306709Early detection of pre-leukaemic clones in the aged haematopoietic compartment using single cell approachesKristina KirschnerLeuka (LEUKA)2019/JGF/003CS - Epigenetics