title: "Inflamm-aging" influences immune cell survival factors in human bone marrow.
abstract: The bone marrow (BM) plays a key role in the long-term maintenance of immunological memory. However, the impact of aging on the production of survival factors for effector/memory T cells and plasma cells in the human BM has not been studied. We now show that the expression of molecules involved in the maintenance of immunological memory in the human BM changes with age. While IL-15, which protects potentially harmful CD8+CD28-senescent T cells, increases, IL-7 decreases. IL-6, which may synergize with IL-15, is also overexpressed. In contrast, a proliferation-inducing ligand, a plasma cell survival factor, is reduced. IFN-y, TNF, and ROS accumulate in the BM in old age. IL-15 and IL-6 expression are stimulated by IFN-y and correlate with ROS levels in BM mononuclear cells. Both cytokines are reduced by incubation with the ROS scavengers N-acetylcysteine and vitamin C. IL-15 and IL-6 are also overexpressed in the BM of superoxide dismutase 1 knockout mice compared to their WT counterparts. In summary, our results demonstrate the role of inflammation and oxidative stress in age-related changes of immune cell survival factors in the BM, suggesting that antioxidants may be beneficial in counteracting immunosenescence by improving immunological memory in old age.
authors.affiliation: Department of Immunology, Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria.
authors.forename: Luca
authors.initials: L
authors.lastname: Pangrazzi
authors.affiliation: Department of Immunology, Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meryk
authors.affiliation: Department of Immunology, Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria.
authors.forename: Erin
authors.initials: E
authors.lastname: Naismith
authors.affiliation: Department of Molecular and Cell Biology, Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria.
authors.forename: Rafal
authors.initials: R
authors.lastname: Koziel
authors.affiliation: Department of Orthopedic Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Julian
authors.initials: J
authors.lastname: Lair
authors.affiliation: Department of Orthopedic Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Krismer
authors.affiliation: Department of Orthopedic Surgery, Hospital Wels-Grieskirchen, Wels, Austria.
authors.forename: Klemens
authors.initials: K
authors.lastname: Trieb
authors.affiliation: Department of Immunology, Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Grubeck-Loebenstein
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000375:Aging / Q000276:immunology*; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007156:Immunologic Memory; D000068884:Immunosenescence; D007249:Inflammation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000378:metabolism; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000072105:Superoxide Dismutase-1; D001205:Ascorbic Acid; D000111:Acetylcysteine
keywords: Aging; Bone marrow; Immunological memory; Immunosenescence; ROS