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

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.

Modelling the role of redox-related mechanisms in musculoskeletal ageing.

The decline in the musculoskeletal system with age is driven at the cellular level by random molecular damage. Cells possess mechanisms to repair or remove damage and many of the pathways involved in this response are regulated by redox signals. However, with ageing there is an increase in oxidative stress which can lead to chronic inflammation and disruption of redox signalling pathways.

PyCoTools: a Python toolbox for COPASI.

Motivation: COPASI is an open source software package for constructing, simulating and analyzing dynamic models of biochemical networks. COPASI is primarily intended to be used with a graphical user interface but often it is desirable to be able to access COPASI features programmatically, with a high level interface.

Results: PyCoTools is a Python package aimed at providing a high level interface to COPASI tasks with an emphasis on model calibration.

'Molecular habituation' as a potential mechanism of gradual homeostatic loss with age.

The ability of reactive oxygen species (ROS) to cause molecular damage has meant that chronic oxidative stress has been mostly studied from the point of view of being a source of toxicity to the cell. However, the known duality of ROS molecules as both damaging agents and cellular redox signals implies another perspective in the study of sustained oxidative stress. This is a perspective of studying oxidative stress as a constitutive signal within the cell.

Systems modelling ageing: from single senescent cells to simple multi-cellular models.

Systems modelling has been successfully used to investigate several key molecular mechanisms of ageing. Modelling frameworks to allow integration of models and methods to enhance confidence in models are now well established. In this article, we discuss these issues and work through the process of building an integrated model for cellular senescence as a single cell and in a simple tissue context.

Modelling the molecular mechanisms of aging.

The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process.