PhD proposal

Supervisors: S. Guyonnet & N. Davezac

Team S. Andrieu (U1027)

The objective is to study the relationship between nutrition and intrinsic capacities and understand the impact of Reactive Oxygen Species (ROS) metabolism in this context. For this, different approaches will be carried out within the framework of the INSPIRE platform to promote healthy aging. First, the epidemiological component will be made from data from human cohorts, aged 70 and over, randomized with multi-domain interventions in order to analyze the link between the nutrition and intrinsic abilities. Existing cohorts (MAPT, NOLAN, COGFRAIL) will be analyzed as well as the ongoing cohort of the INSPIRE project. We developed a mathematical model centred on the mitochondrial dysfunctions and more precisely on the dysfunction of mitochondrial respiratory chain (MRC) as it was shown to be a major point in ROS production (80% of total ROS production).

The MRC can be divided in two models, one concerning Complex I and the other concerning Complex III as they are the principal providers of ROS. Detoxification of ROS in the mitochondria and then in the cytoplasm is being added. The PhD student will perform biological experiments to determine biological parameters with different quantities of NADH substrates of the MRC and different antioxidant component to mimic the different food intakes and modulate ROS metabolism. This system-level model, which has been built taking into account the desired level of detail, is then used to explain, predict and analyse the behaviours of the biological system. Thus, it becomes possible to use the model as a way of proving hypothesis and performing predictions. This translational study will help to better understand the fundamental mechanisms of aging associating alimentation and intrinsic abilities as well as molecular level with ROS production, and in the long term, to offer treatments as well as predict and / or prevent the onset of pathologies in humans.

Key words: ROS, nutrition, mathematics