Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression

Figure 2

A global model of neuroprogressive changes in aging and anxiety. CMI and inflammatory responses are accompanied by activation of O&NS with production of increased ROS/RNS. ROS/RNS can react with proteins, fatty acids (including ω-3 PUFAs), and DNA and change their chemical structure which became immunogenic and produce an autoimmune response. Both O&NS and CMI inflammation are implicated in beta-amyloid formation and telomeres shortening. Moreover, increased O&NS impairs mitochondrial function with further production of ROS and macromolecular damage. PICs activate IDO which causes depletion of tryptophan/5-HT and the synthesis of tryptophan catabolites (TRYCATs). Some of these TRYCATs (kynurenine and quinolinic acid) are anxiogenic and neurotoxic. The lipopolysaccharide (LPS), caused by bacterial translocation from the gut, may aggravate existing inflammation and O&NS or trigger a primary inflammatory response. LPS and lowered ω3 are associated with decreased neurogenesis. CMI: cell-mediated immune; PICs: proinflammatory cytokines; IL-1β: interleukin-1β; IL-6: interleukin-6; TNF-α: tumor necrosis factor-α; IFN-γ: interferon-gamma; O&NS: oxidative and nitrosative stress; ROS: reactive oxygen species; RNS: reactive nitrogen species; IDO: indoleamine 2,3-dioxygenase; TRYCATs: L-tryptophan catabolites; LPS: lipopolysaccharide (a component of the outer membrane of Gram-negative bacteria); ω-3 PUFAs: omega-3 polyunsaturated fatty acids.