title: Neuroendocrine and viral correlates of premature immunosenescence.
abstract: Aging continuously remodels the immune system, a process known as immunosenescence. Here, we review evidence of premature immunosenescence in younger individuals under conditions of chronic psychological stress, chronic inflammation, or exposure to certain persistent viral infections. Chronic stress may accelerate various features of immunosenescence by activating key allostatic systems, notably the hypothalamic-pituitary-adrenal axis and increased cortisol levels. Chronic stress is associated with thymic involution, blunted T cell proliferation, increased serum proinflammatory markers, and shorter telomere lengths. Human cytomegalovirus (CMV) infection has been implicated in accelerating immunosenescence by shrinking the T cell receptor repertoire and causing clonal expansion of senescent CD8(+) CD28(-) T cells with a proinflammatory profile. These factors increase inflammation associated with aging, or "inflammaging," particularly as it relates to etiology of several age-related diseases and increased mortality. Patients with rheumatoid arthritis have been shown to have several signatures of premature immunosenescence, including expansion of senescent T cells associated with cognitive impairment. We end by speculating that bipolar disorder can be considered as a model of accelerated aging because it has been associated with shortened telomeres, higher CMV IgG titers, and expansion of senescent and regulatory T cells.
authors.affiliation: Laboratory of Immunosenescence, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
authors.forename: Moisés E
authors.initials: ME
authors.lastname: Bauer
authors.affiliation: Laboratory of Immunosenescence, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wieck
authors.affiliation: Laboratory of Immunosenescence, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Petersen
authors.affiliation: Laboratory of Immunosenescence, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
authors.forename: Talita S A
authors.initials: TS
authors.lastname: Baptista
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology; D001714:Bipolar Disorder / Q000276:immunology; D016922:Cellular Senescence / Q000235:genetics; D020805:Central Nervous System Viral Diseases / Q000276:immunology / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D000068884:Immunosenescence / Q000276:immunology / Q000502:physiology*; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D009490:Neurosecretory Systems / Q000276:immunology / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013315:Stress, Psychological / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D005938:Glucocorticoids; D011948:Receptors, Antigen, T-Cell
keywords: aging; cytomegalovirus; glucocorticoids; immunosenescence; lymphocytes; psychological stress