Changes in primary lymphoid organs with aging

Ivan K. Chinn, Clare C. Blackburn, Nancy R. Manley, Gregory D. Sempowski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)309-320
Number of pages12
JournalSeminars in immunology
Volume24
Issue number5
DOIs
Publication statusPublished - 1 Oct 2012

Keywords

  • Aging
  • Bone marrow
  • Lymphopoiesis
  • Stroma
  • Thymopoiesis
  • Thymus

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