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Lookup NU author(s): Dr Alvaro Martinez Guimera, Dr Peter Clark, Dr James Wordsworth, Dr Daryl Shanley
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
The regulation of mitochondrial turnover under conditions of stress occurs partly through the AMPK-NAD+-PGC1α-SIRT1 signalling pathway. This pathway can be affected by both genomic instability and chronic inflammation since these will result in an increased rate of NAD+ degradation through PARP1 and CD38 respectively. In this work we develop a computational model of this signalling pathway, calibrating and validating it against experimental data. The computational model is used to study mitochondrial turnover under conditions of stress and how it is affected by genomic instability, chronic inflammation and biological ageing in general. We report that the AMPK-NAD+-PGC1α-SIRT1 signalling pathway becomes less responsive with age and that this can prime for the accumulation of dysfunctional mitochondria.
Author(s): Martinez-Guimera A, Clark P, Wordsworth J, Anugula S, Rasmussen LJ, Shanley DP
Publication type: Article
Publication status: Published
Journal: Experimental Gerontology
Year: 2022
Volume: 166
Print publication date: 01/09/2022
Online publication date: 07/07/2022
Acceptance date: 04/07/2022
Date deposited: 08/03/2024
ISSN (print): 0531-5565
ISSN (electronic): 1873-6815
Publisher: Elsevier
URL: https://doi.org/10.1016/j.exger.2022.111889
DOI: 10.1016/j.exger.2022.111889
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