The impact of aging and age-related diseases has dramatically increased in our society: First, aging individuals are particularly susceptible to infections as a result of both disease and therapeutic interventions. Second, our prophylactic interventions are customized for toddlers, children and young adults. Third, there is a constellation of age-associated detrimental changes in the function of the immune system, loosely termed “immunosenescence”, which results in greater susceptibility to infection and reduced responses to vaccination. However, the exact causes of the functional alterations observed in the immune system of aging individuals are still unclear. The GERONTOSHIELD consortium will pursue a Systems Biology-driven approach to understand the molecular processes affected during immunosenescence to derive strategies to overcome them in order to establish immune interventions tailored for the elderly.
Murine and human systems will be exploited to reverse engineer immunosenescence, i.e. to discover the molecular processes of it. In vitro modeling studies will allow us to assess whether similar processes take place in murine and human cells, crucial for implementation. The emerging data will assist in developing mathematical models defining the involved processes, which will enable the generation of hypotheses on the underlying mechanisms. This will be an iterative process intertwining modeling and experimentation, in which the models will be progressively fine-tuned. Further, the establishment of a holistic phenomenological in silico model for influenza infection and in vivo immunization studies using flu antigens in mice will allow understanding the dynamics of responses to infection and vaccination in the context of immunosenescence, thereby paving the road for the translation of this knowledge and tools into improved medical treatments that are tailored for the elderly.