Background: Resilience is the ability to achieve a positive outcome when we are in the
face of adversity. It supposes an active resistance to adversity by coping mechanisms in which genetic,
molecular, neural and environmental factors are involved. Resilience has been usually studied
in early ages and few is known about it during aging.
Methods: In this review, we will address the age-related changes in the brain mechanisms involved
in regulating the stress response. Furthermore, using the EE paradigm, we analyse the resilient potential
of this intervention and its neurobiological basis. In this case, we will focus on identifying the
characteristics of a resilient brain (modifications in HPA structure and function, neurogenesis, specific
neuron types, glia, neurotrophic factors, nitric oxide synthase or microRNAs, among others).
Results: The evidence suggests that a healthy lifestyle has a crucial role to promote a resilient brain
during aging. Along with the behavioral changes described, a better regulation of HPA axis, enhanced
levels of postmitotic type-3 cells or changes in GABAergic neurotransmission are some of
the brain mechanisms involved in resilience.
Conclusion: Future research should identify different biomarkers that increase the resistance to
develop mood disorders and based on this knowledge, develop new potential therapeutic targets.