• Mathematical modelling of metabolic regulation in aging

      Mc Auley, Mark T.; Mooney, Kathleen M.; Angell, Peter J.; Wilkinson, Stephen J.; University of Chester ; Liverpool Hope University ; Edge Hill University ; University of Chester (MDPI, 2015-04-27)
      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.
    • The role of Mathematical Modelling in understanding Aging

      Mc Auley, Mark T.; Morgan, Amy; Mooney, Kathleen M.; University of Chester, Edgehill University (CRC Press, 2017-10-25)
      Mathematical models have played key roles in developing our understanding of aging. The first pioneering mathematical models evaluated aging from an evolutionary perspective, generating meaningful insights into why aging occurs and laid the foundations for our current understanding of aging. More recently mathematical models have been used to gain a deeper understanding of the intracellular mechanisms associated with intrinsic aging. This chapter will outline what mathematical modelling is, and the advantages it has over more conventional approaches used in biogerontology. The steps involved in assembling a model will also be described and the leading theoretical frameworks underpinning them will be outlined. Moreover, we discuss in detail a variety of aging focused mechanistic mathematical models which have been developed in recent years. The chapter concludes by challenging the community to develop a unified mechanistic mathematical model which can be used to examine aging in a more integrated fashion.