title: Mitochondrial allostatic load puts the 'gluc' back in glucocorticoids.
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.
authors.affiliation: Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia and the University of Pennsylvania, 3501 Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Picard
authors.affiliation: Integrated Program in Neuroscience, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada.
authors.forename: Robert-Paul
authors.initials: RP
authors.lastname: Juster
authors.affiliation: Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: McEwen
mesh_terms: D000375:Aging / Q000502:physiology; D052636:Allostasis / Q000502:physiology*; D000818:Animals; D016922:Cellular Senescence / Q000502:physiology; D004272:DNA, Mitochondrial / Q000502:physiology; D005938:Glucocorticoids / Q000502:physiology*; D005947:Glucose / Q000502:physiology; D006262:Health; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology
chemical_list: D004272:DNA, Mitochondrial; D005938:Glucocorticoids; D005947:Glucose