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Sublethal whole-body irradiation causes progressive premature frailty in mice

Lookup NU author(s): Edward Fielder, Julien Agneessens, Brigid Griffin, Dr Craig Parker, Dr Satomi Miwa, Professor Thomas von Zglinicki

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 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.


Publication metadata

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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