Systems modelling predicts chronic inflammation and genomic instability prevent effective mitochondrial regulation during biological ageing

Research output: Contribution to journal › Review › Research › peer-review

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Systems modelling predicts chronic inflammation and genomic instability prevent effective mitochondrial regulation during biological ageing. / Guimera, Alvaro Martinez; Clark, Peter; Wordsworth, James; Anugula, Sharath; Rasmussen, Lene Juel; Shanley, Daryl P.

In: Experimental Gerontology, Vol. 166, 111889, 2022.

Research output: Contribution to journal › Review › Research › peer-review

Harvard

Guimera, AM, Clark, P, Wordsworth, J, Anugula, S, Rasmussen, LJ & Shanley, DP 2022, 'Systems modelling predicts chronic inflammation and genomic instability prevent effective mitochondrial regulation during biological ageing', Experimental Gerontology, vol. 166, 111889. https://doi.org/10.1016/j.exger.2022.111889

APA

Guimera, A. M., Clark, P., Wordsworth, J., Anugula, S., Rasmussen, L. J., & Shanley, D. P. (2022). Systems modelling predicts chronic inflammation and genomic instability prevent effective mitochondrial regulation during biological ageing. Experimental Gerontology, 166, [111889]. https://doi.org/10.1016/j.exger.2022.111889

Vancouver

Guimera AM, Clark P, Wordsworth J, Anugula S, Rasmussen LJ, Shanley DP. Systems modelling predicts chronic inflammation and genomic instability prevent effective mitochondrial regulation during biological ageing. Experimental Gerontology. 2022;166. 111889. https://doi.org/10.1016/j.exger.2022.111889

Author

Guimera, Alvaro Martinez ; Clark, Peter ; Wordsworth, James ; Anugula, Sharath ; Rasmussen, Lene Juel ; Shanley, Daryl P. / Systems modelling predicts chronic inflammation and genomic instability prevent effective mitochondrial regulation during biological ageing. In: Experimental Gerontology. 2022 ; Vol. 166.

Bibtex

@article{a8369f23b69f4ffa9b42413844b890ab,

title = "Systems modelling predicts chronic inflammation and genomic instability prevent effective mitochondrial regulation during biological ageing",

abstract = "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.",

keywords = "Cell Signalling, DNA damage, Mito-nuclear communication, Mitochondria, NAD, Systems modelling",

author = "Guimera, {Alvaro Martinez} and Peter Clark and James Wordsworth and Sharath Anugula and Rasmussen, {Lene Juel} and Shanley, {Daryl P.}",

note = "Publisher Copyright: {\textcopyright} 2022",

year = "2022",

doi = "10.1016/j.exger.2022.111889",

language = "English",

volume = "166",

journal = "Experimental Gerontology",

issn = "0531-5565",

publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Systems modelling predicts chronic inflammation and genomic instability prevent effective mitochondrial regulation during biological ageing

AU - Guimera, Alvaro Martinez

AU - Clark, Peter

AU - Wordsworth, James

AU - Anugula, Sharath

AU - Rasmussen, Lene Juel

AU - Shanley, Daryl P.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Cell Signalling

KW - DNA damage

KW - Mito-nuclear communication

KW - Mitochondria

KW - NAD

KW - Systems modelling

U2 - 10.1016/j.exger.2022.111889

DO - 10.1016/j.exger.2022.111889

M3 - Review

C2 - 35811018

AN - SCOPUS:85133598201

VL - 166

JO - Experimental Gerontology

JF - Experimental Gerontology

SN - 0531-5565

M1 - 111889

ER -

ID: 343337666

Center for Healthy Aging