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)

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 > School 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
306709		Early detection of pre-leukaemic clones in the aged haematopoietic compartment using single cell approaches	Kristina Kirschner	Leuka (LEUKA)	2019/JGF/003	CS - Epigenetics