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Changes in primary lymphoid organs with aging.

TitleChanges in primary lymphoid organs with aging.
Publication TypeJournal Article
Year of Publication2012
AuthorsChinn IK, C Blackburn C, Manley NR, Sempowski GD
JournalSemin Immunol
Volume24
Issue5
Pagination309-20
Date Published2012 Oct
ISSN1096-3618
KeywordsAging, Animals, Bone Marrow, Cell Hypoxia, Humans, Immunity, Innate, Lymphatic System, Oxidative Stress
Abstract

Aging is associated with decreased immune function that leads to increased morbidity and mortality in the elderly. Immune senescence is accompanied by age-related changes in two primary lymphoid organs, bone marrow and thymus, that result in decreased production and function of B and T lymphocytes. In bone marrow, hematopoietic stem cells exhibit reduced self-renewal potential, increased skewing toward myelopoiesis, and decreased production of lymphocytes with aging. These functional sequelae of aging are caused in part by increased oxidative stress, inflammation, adipocyte differentiation, and disruption of hypoxic osteoblastic niches. In thymus, aging is associated with tissue involution, exhibited by a disorganization of the thymic epithelial cell architecture and increased adiposity. This dysregulation correlates with a loss of stroma-thymocyte 'cross-talk', resulting in decreased export of naïve T cells. Mounting evidence argues that with aging, thymic inflammation, systemic stress, local Foxn1 and keratinocyte growth factor expression, and sex steroid levels play critical roles in actively driving thymic involution and overall adaptive immune senescence across the lifespan. With a better understanding of the complex mechanisms and pathways that mediate bone marrow and thymus involution with aging, potential increases for the development of safe and effective interventions to prevent or restore loss of immune function with aging.

DOI10.1016/j.smim.2012.04.005
Alternate JournalSemin. Immunol.
PubMed ID22559987
PubMed Central IDPMC3415579
Grant ListAG025150 / AG / NIA NIH HHS / United States
AG035302 / AG / NIA NIH HHS / United States
AI076514 / AI / NIAID NIH HHS / United States
AI082127 / AI / NIAID NIH HHS / United States
HD043494 / HD / NICHD NIH HHS / United States
HHSN272200900059C / / PHS HHS / United States
K12 HD043494 / HD / NICHD NIH HHS / United States
K12 HD043494-10 / HD / NICHD NIH HHS / United States
P01 AI076514-02 / AI / NIAID NIH HHS / United States
R01 AG025150 / AG / NIA NIH HHS / United States
R01 AG025150-05 / AG / NIA NIH HHS / United States
R01 AG035302-03 / AG / NIA NIH HHS / United States
R01 AI055001-05 / AI / NIAID NIH HHS / United States
R01 AI082127 / AI / NIAID NIH HHS / United States
R01 AI082127-05 / AI / NIAID NIH HHS / United States
/ / Biotechnology and Biological Sciences Research Council / United Kingdom