Space agencies have developed extensive expertise with sustaining human presence in low earth orbits and microgravity. Prolonged human presence in space beyond EarthâĂŹs orbit presents additional, some still unsolved issues. These are linked to the distance to Earth (impossibility of effective tele-operation, psychological effects linked to remoteness from Earth, required autonomy, the handling of emergencies, long mission durations), and to the environments beyond the Earth magnetosphere (radiation levels, local environments including atmospheres, dust, gravity, day-night cycles). These issues have impacts on the spacecraft design, the mission operations, astronaut selection and preparation and required supporting/ enabling technologies. This paper builds upon previous work by Rossini et al. , in critically reviewing and updating the current state of scientific research on enhancing astronaut's capabilities to face some of these challenges. In particular, it discusses the pertinence and feasibility of two approaches aiming at enhancing the chances of success of human missions: induced hibernation state and brain-machine interfaces.