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Lookup NU author(s): Dr Edward FielderORCiD, Julien Agneessens, Brigid Griffin, Dr Craig Parker, Dr Satomi Miwa, Professor Thomas von Zglinicki
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2019 There is an unmet need to develop and validate therapies that can treat or at least prevent premature therapy-induced frailty, multi-morbidity and mortality in long-term tumour survivors. In an approach to develop a first mouse model for therapy-induced long-term frailty, we irradiated male C57Bl/6 mice at 5–6 months of age sub-lethally with 3 × 3 Gy (whole body) and assessed subsequent frailty for up to 6 months using a Rockwood-type frailty index (FI). Frailty scorers were trained to obtain excellent inter- and intra-observer reproducibility. Irradiated mice developed progressive frailty approximately twice as fast as controls. This was premature frailty; it was phenotypically identical to that in non-irradiated mice at higher age. As expected, frailty was associated with decreased cognition and predicted mortality. In irradiated mice, frailty and neuromuscular performance, measured by Rotarod and Hanging Wire tests, were not associated with each other, probably because of long-term decreased body weights after irradiation. We conclude that progressive frailty following sub-lethal irradiation comprises a sensitive and easy to use test bed for interventions to stop premature ageing in long-term tumour survivors.
Author(s): Fielder E, Weigand M, Agneessens J, Griffin B, Parker C, Miwa S, von Zglinicki T
Publication type: Article
Publication status: Published
Journal: Mechanisms of Ageing and Development
Year: 2019
Volume: 180
Pages: 63-69
Print publication date: 01/06/2019
Online publication date: 04/04/2019
Acceptance date: 26/03/2019
Date deposited: 23/04/2019
ISSN (print): 0047-6374
ISSN (electronic): 1872-6216
Publisher: Elsevier Ireland Ltd
URL: https://doi.org/10.1016/j.mad.2019.03.006
DOI: 10.1016/j.mad.2019.03.006
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