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Mathematical Modelling of Metabolic Regulation in Aging

Faculty of Science & Engineering, University of Chester, Thornton Science Park, CH2 4NU, UK
Faculty of Health and Social Care, Edge Hill University, Ormskirk, Lancashire, L39 4QP, UK
School of Health Sciences, Liverpool Hope University, Taggart Avenue, Liverpool, L16 9JD, UK
Author to whom correspondence should be addressed.
Academic Editor: Christoph Kaleta
Metabolites 2015, 5(2), 232-251;
Received: 3 November 2014 / Revised: 24 March 2015 / Accepted: 25 March 2015 / Published: 27 April 2015
(This article belongs to the Special Issue Metabolism and Systems Biology)
PDF [695 KB, uploaded 4 May 2015]


The underlying cellular mechanisms that characterize aging are complex and multifaceted. However, it is emerging that aging could be regulated by two distinct metabolic hubs. These hubs are the pathway defined by the mammalian target of rapamycin (mTOR) and that defined by the NAD+-dependent deacetylase enzyme, SIRT1. Recent experimental evidence suggests that there is crosstalk between these two important pathways; however, the mechanisms underpinning their interaction(s) remains poorly understood. In this review, we propose using computational modelling in tandem with experimentation to delineate the mechanism(s). We briefly discuss the main modelling frameworks that could be used to disentangle this relationship and present a reduced reaction pathway that could be modelled. We conclude by outlining the limitations of computational modelling and by discussing opportunities for future progress in this area. View Full-Text
Keywords: aging; computational modelling; mammalian target of rapamycin; systems biology; simulation; sirtuins; SIRT1; regulatory network aging; computational modelling; mammalian target of rapamycin; systems biology; simulation; sirtuins; SIRT1; regulatory network

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Mc Auley, M.T.; Mooney, K.M.; Angell, P.J.; Wilkinson, S.J. Mathematical Modelling of Metabolic Regulation in Aging. Metabolites 2015, 5, 232-251.

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