The thymus — the organ that trains T-cells — shrinks with age, leaving older adults with fewer naïve T-cells and weakened immunity. NIH researchers engineered two mouse models where the transcription factor Myc was either constantly or inducibly expressed in thymic epithelial cells (TECs), preventing or reversing age-related thymic shrinkage. Middle-aged mice with enhanced thymic function had more naïve CD4 and CD8 T-cells in circulation, better antibody responses to immunization, and dramatically improved survival after Toxoplasma gondii infection. Enhanced thymic function also rebalanced regulatory T-cells and preserved Th1 immune signatures in conventional T-cells. The findings provide direct causal evidence that thymic decline drives immune vulnerability in aging and support thymic regeneration as a viable longevity strategy.
