Persistent degenerative changes in thymic organ function revealed by an inducible model of organ regrowth

Ann V. Griffith, Mohammad Fallahi, Thomas Venables, Howard T. Petrie

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

The thymus is the most rapidly aging tissue in the body, with progressive atrophy beginning as early as birth and not later than adolescence. Latent regenerative potential exists in the atrophic thymus, because certain stimuli can induce quantitative regrowth, but qualitative function of T lymphocytes produced by the regenerated organ has not been fully assessed. Using a genome-wide computational approach, we show that accelerated thymic aging is primarily a function of stromal cells, and that while overall cellularity of the thymus can be restored, many other aspects of thymic function cannot. Medullary islet complexity and tissue-restricted antigen expression decrease with age, representing potential mechanisms for age-related increases in autoimmune disease, but neither of these is restored by induced regrowth, suggesting that new T cells produced by the regrown thymus will probably include more autoreactive cells. Global analysis of stromal gene expression profiles implicates widespread changes in Wnt signaling as the most significant hallmark of degeneration, changes that once again persist even at peak regrowth. Consistent with the permanent nature of age-related molecular changes in stromal cells, induced thymic regrowth is not durable, with the regrown organ returning to an atrophic state within 2weeks of reaching peak size. Our findings indicate that while quantitative regrowth of the thymus is achievable, the changes associated with aging persist, including potential negative implications for autoimmunity.

Original languageEnglish (US)
Pages (from-to)169-177
Number of pages9
JournalAging cell
Volume11
Issue number1
DOIs
StatePublished - Feb 2012
Externally publishedYes

Keywords

  • Aging
  • Computational biology
  • Regenerative medicine
  • Stromal cells
  • Thymus

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Fingerprint Dive into the research topics of 'Persistent degenerative changes in thymic organ function revealed by an inducible model of organ regrowth'. Together they form a unique fingerprint.

Cite this