Mathematical modelling of metabolic regulation in aging.
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.
Faculty of Science & Engineering, University of Chester, Thornton Science Park, CH2 4NU, UK. m.mcauley@chester.ac.uk.
Mark T Mc
MT
Auley
Faculty of Health and Social Care, Edge Hill University, Ormskirk, Lancashire, L39 4QP, UK. kathleen.mooney@edgehill.ac.uk.
Kathleen M
KM
Mooney
School of Health Sciences, Liverpool Hope University, Taggart Avenue, Liverpool, L16 9JD, UK. angellp@hope.ac.uk.
Peter J
PJ
Angell
Faculty of Science & Engineering, University of Chester, Thornton Science Park, CH2 4NU, UK. s.j.wilkinson@chester.ac.uk.
Stephen J
SJ
Wilkinson