Figure 1. Mechanisms of stress-induced metabolic changes.

The figure summarizes major neuroendocrine pathways and behavioural disorders implicated in chronic stress, affecting (either directly or indirectly) metabolic functions, risk of metabolic disease and the pace of biological ageing. Major stress-related pathways include: The Hypothalamus Pituitary Adrenocortical (HPA) axis secreted hormones, such as corticotrophin releasing factor (CRH), adrenocorticotrophin hormone (ACTH) and cortisol; the Sympatho-Adreno-Medullary axis secreted catecholamines (epinephrine>>norepinephrine), granins and other hormones and neuropeptides³⁴; the Sympathetic Nervous System (SNS) secreted neurotransmitters, including norepinephrine, ATP, Neuropetide Y (NPY) and other factors^35,36; and the Parasympathetic Nervous System (PNS) secreted neurotransmitters, such as acetylcholine (ACh) and other factors. SNS activation and PNS withdrawal contribute to stress reactions whereas PNS activation facilitates recovery^11,19. In addition to classical stress-associated metabolic regulators (such as insulin), glucagon and several cytokines, myokines and osteocalcin³⁷ have been recently identified as regulators of the stress response. In addition, growing evidence suggest that stress can induce markers of immune senescence, DNA methylation and accumulation of senescent cells in multiple metabolic organs, including the liver, adipose and the brain^20,38-41,74.