Editorial: Brain Basis of Resilience and its Effect on Mood Disorders in the Aging.

A growing field of research has emerged on the concept of resilience among older adults and its role in successful aging. The successful aging has several components, but it is typically defined as freedom from chronic disease and disability, as well as high physical and mental functioning [1]. High resilience later in life has been associated with optimal outcomes, such as reduced depression and mortality risk [2-5], as well as better self-perception of successful aging [1, 6], increased quality of life and improved lifestyle behaviors. Therefore, in the present issue, we aimed to provide a comprehensive review of the literature on aging and resilience by selected experts.

Recent evidence has suggested that sedentary lifestyle and poor diet have a role in the onset and course of depression and anxiety disorders [7, 8]. Hence, Dr. Farioli-Vecchioli and Dr. Cutuli reviewed on the potential positive effects of physical exercise and nutritional factors, such as Omega-3 fatty acids, on psychiatric disorders during aging.

Gene-environment interactions can have lasting consequences on brain structure and function, potentially contributing to diverse neuropsychiatric phenotypes [9, 10]. Dr. Zannas revised the evidence showing how gene-stress interactions can impact the aging brain and related phenotypes in late life. The author also discussed the potential mechanisms underlying such gene-environment interactions and their implications for the prevention and treatment of late-life neuropsychiatric syndromes.

Thirdly, Dr. Faye et al. summarized neurobiological factors underlying stress resilience, with particular focus on the serotoninergic (5HT), glutamatergic, and γ-Aminobutyric acid (GABA) systems, as well as the hypothalamic-pituitary-adrenal (HPA) axis in rodents and humans [11-14]. Finally, they discussed stress resilience in the context of aging, as the likelihood of mood disorders increases in older adults. Interestingly, increased resilience has been shown to slow aging and improved overall health.

One of the greatest challenges of the neuroscience research is to identify biological agents that increase resistance to develop pathological responses to stress throughout life. Thus, Dr. Moreno-Fernández et al. suggest that LPA1-receptor could be one of these agents [15, 16]. This receptor is one of the six G protein-coupled receptors through which lysophosphatidic acid acts and has been recently involved in emotional regulation. In fact, the reviewed evidence illustrate the relevance of the LPA-LPA1 pathway in adaptive stress coping and shed light on a potential specific mechanism of stress resilience in the aging.

On the other hand, many studies have shown an important role of glutamatergic system in major depressive disorder [17, 18]. Experimental and clinical data suggest that attenuation of N-methyl-D-aspartate (NMDA) receptor function exerts antidepressant effects. In this sense, Dr. Reús and Dr. Quevedo highlighted findings from animal and human studies identifying the role of glutamatergic system in resilience.

Finally, Dr. Sampedro-Piquero et al. helped the reader to improve their understanding about age-related changes in the brain mechanisms involved in regulating the stress response. Furthermore, this review focused 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). For example, a better regulation of HPA axis [14], enhanced levels of postmitotic type-3 cells [19, 20] or changes in GABAergic neurotransmission [13] are some of the brain mechanisms involved in resilience.

In conclusion, the aim of this special issue was to give an insight into the current research of neurobiological mechanisms underlying resilience and its impact during aging.