The role of preconditioning in the development of resilience: Mechanistic insights

Whilst most body tissues have an intrinsic ability to withstand day-to-day stresses, even more intriguing (and of enormous clinical potential) is the striking adaptive responses to stress that drive increased ‘resilience’ against further insult. Numerous species are now known to exploit these ‘preconditioning’ (hormetic-like) responses to boost their resistance to a range of stressors (including ischemia, radiation and nutrient deprivation). Here, we review recent studies in model and less-traditional organisms that are accelerating our mechanistic understanding of these phenomena; we highlight cutting-edge research implicating a role for immune cells, altered cellular metabolism through to exosomes and epigenetics. Given the emerging complexity of tissue preconditioning, detailed mechanistic understanding will no doubt prove critical for the therapeutic activation of these remarkable responses.