No abstract

The link between chronic psychosocial and metabolic stress and the pathogenesis of disease has been extensively documented. Nevertheless, the cellular mechanisms by which stressful life experiences and their associated primary neuroendocrine mediators cause biological damage and increase disease risk remain poorly understood. The allostatic load model of chronic stress focuses on glucocorticoid dysregulation. In this Perspectives, we expand upon the metabolic aspects of this model-particularly glucose imbalance-and propose that mitochondrial dysfunction constitutes an early, modifiable target of chronic stress and stress-related health behaviours. Central to this process is mitochondrial regulation of energy metabolism and cellular signalling. Chronically elevated glucose levels damage both mitochondria and mitochondrial DNA, generating toxic products that can promote systemic inflammation, alter gene expression and hasten cell ageing. Consequently, the concept of 'mitochondrial allostatic load' defines the deleterious structural and functional changes that mitochondria undergo in response to elevated glucose levels and stress-related pathophysiology.

This review aims to discuss the evidence supporting the link between chronic stress, cognitive function and mental health. Over the years, the associations between these concepts have been investigated in different populations. This review summarizes the findings that have emerged from older populations as well as from populations suffering from pathological aging, namely Mild Cognitive Impairment and Alzheimer's Disease. Although older adults are an interesting population to study in terms of chronic stress, other stress-related diseases can occur throughout the lifespan. The second section covers some of these stress-related diseases that have recently received a great deal of attention, namely burnout, depression, and post-traumatic stress disorder. Given that chronic stress contributes to the development of certain pathologies by accelerating and/or exacerbating pre-existing vulnerabilities that vary from one individual to the other, the final section summarizes data obtained on potential variables contributing to the association between chronic stress and cognition.