title: Impact of immune-metabolic interactions on age-related thymic demise and T cell senescence.
abstract: Emerging evidence indicates that the immune and metabolic interactions control several aspects of the aging process and associated chronic diseases. Among several sites of immune-metabolic interactions, thymic demise represents a particularly puzzling phenomenon because even in metabolically healthy middle-aged individuals the majority of thymic space is replaced with ectopic lipids. The new T cell specificities can only be generated in a functional thymus and, peripheral proliferation of pre-existing T cell clones provides limited immune-vigilance in the elderly. Therefore, it is hypothesized that the strategies that enhance thymic-lymphopoiesis may extend healthspan. Recent data suggest that byproducts of thymic fatty acids and lipids result in accumulation of 'lipotoxic DAMPs' (damage associated molecular patterns), which triggers the innate immune-sensing mechanism like inflammasome activation which links aging to thymic demise. The immune-metabolic interaction within the aging thymus produces a local pro-inflammatory state that directly compromises the thymic stromal microenvironment, thymic-lymphopoiesis and serves a precursor of systemic immune-dysregulation in the elderly. New evidence also suggests that ectopic thymic adipocytes may develop from specific intrathymic stromal cell precursors instead of a passive process that is simply a consequence of thymic lymphopenia. Thus the complex bidirectional interactions between metabolic and immune systems may link aging to health, T cell senescence, and associated diseases. This review discusses the immune-metabolic mechanisms during aging - with implications for developing future therapeutic strategies for living well beyond the expected.
authors.affiliation: Immunobiology Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, United States. Vishwa.Dixit@pbrc.edu
authors.forename: Vishwa Deep
authors.initials: VD
authors.lastname: Dixit
mesh_terms: D000375:Aging; D000818:Animals; D016922:Cellular Senescence; D006801:Humans; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism