<title>Abstract</title> Rejuvenation restores cellular function lost with age, but it is not known to confer properties the cell lacked in its younger past. We found that Disruptors of sestrin-MAPK interactions (DOS) reprogramed senescent T cells into new stem like T clones with different T cell receptors (TCRs). DOS targeted sestrin-MAPK complexes (sMAC) to ubiquitin-dependent proteasomal degradation, resulting in long-term sestrin transcriptional inhibition, increased T cell fitness, and generation of long-lived stem like memory clones. Strikingly, DOS reactivated juvenile related Rag re-expression, leading to antigen-specific TCR rearrangements in formerly senescent cells. As such, rejuvenated T cells, with stem features and new TCRs, combated multiple lethal challenges never previously encountered in their lifetime, with no need for vaccination. T cell rejuvenation confers new properties whilst preserving cellular state, which unravels an unknown rejuvenating principle in biological systems.