A mathematical model of the effect of aging on bone marrow cells colonizing the thymus

Ramit Mehr, Loya Abel, Paolo Ubezio, Amiela Globerson, Zvia Agur

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


The process of T cell generation in the thymus involves complex cell-cell interactions between the various types of thymic stromal cells, thymocyte progenitors, thymocytes at different stages of differentiation and external factors. We applied the tool of mathematical modelling to analyze hypotheses and direct experiments concerning mechanisms underlying the observed developmental inferiority of bone-marrow thymocyte progenitors from old mice. Previous experimental data showed that lower cell numbers were obtained from old bone marrow-derived thymocyte progenitors, compared to young bone marrow-derived progenitors, when colonizing simultaneously the same fetal thymus. In this study, simulations based on the mathematical model indicate that the developmental inferiority of old bone marrow-derived progenitors cannot be explained by a change in a single parameter, such as the observed differences in progenitor frequency, an increase in cell cycle duration, a reduction in the fraction of proliferating cells in old age, and/or an increase in the rate of cell death. We have performed experimental measurements of the fractions of cycling cells. No significant difference was found between these fractions in young and old bone marrow-derived thymocytes. The difference in developmental patterns of young and old bone marrow-derived thymocytes may be due to a combination of more than one mechanism, possibly including interactions between competing thymocytes of old and young bone marrow origin.

Original languageEnglish
Pages (from-to)159-172
Number of pages14
JournalMechanisms of Ageing and Development
Issue number1-2
StatePublished - Feb 1993
Externally publishedYes


  • Aging
  • Mathematical model
  • Simulations
  • T cell development
  • Thymus


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