The "adaptive reuse" of the building heritage should be linked to an adequate response to needs of people who use the spaces itself, in terms of functionality. Since the historical buildings are protected sites it is often impossible to modify the internal layout in order to achieve the requirements imposed by the prescriptive rules. This paper aims to show the approach used to ensure the Life Safety in an Italian Villa that has been chosen to be reused as University building. The old ancient estate is spread out over 4 floors, connected by wide monumental stairs, and all the didactic activities will take place within the building (in classrooms, laboratories, study-rooms, common areas, etc.). Furthermore, the new furniture, that will be used in the building, will be supported by a certificate of European fire classification, in accordance with the Italian Guidelines. The main features of the performance based design, such as the choice of performance levels, the definition of fire scenarios and the analyses based on advanced thermo-fluid-dynamics will be presented in the following paper. In particular, an accurate analysis of the development of the fire and smoke spread has been performed using Fire Dynamics Simulator (FDS) 6.6.0. The analysis of the human wayfinding has led to develop new strategies for the evacuation in emergencies. In particular, the Intelligent Active Dynamic Signage System has been considered to redirect people, indicating the viable and non-viable exits, depending on the position of the fire source identified by the automatic detection system. These solutions have a low impact on the building since they do not need any layout modifications. In contrary to "passive" signage, "active" (intelligent) wayfinding systems monitor human egress process, spreading of the fire and damages to building, and suggests the best escape paths depending on these conditions.