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This study investigated the cell type primarily responsible for this effect. We reconstituted old mice with BM cells from young or old mice and found that the number of stem cell antigen 1 (Sca-1) cells homing to the heart was significantly greater in young than old chimeras. We then reconstituted old mice with young BM Sca-1<jats:sup>+<\/jats:sup>or Sca-1<jats:sup>\u2212<\/jats:sup>cells. We found that Sca-1 cells repopulated the recipient BM and homed to the heart. The number of BM-derived cells in the aged myocardium co-expressing PDGFR\u03b2 was 3 times greater in Sca-1<jats:sup>+<\/jats:sup>than Sca-1<jats:sup>\u2212<\/jats:sup>chimeric mice. Sca-1<jats:sup>+<\/jats:sup>chimeras had more active cell proliferation in the infarcted heart and improved ventricular function after MI. The improved regeneration involved activation of the PDGFR\u03b2\/Akt\/p27<jats:sup>Kip1<\/jats:sup>pathway. Sca-1<jats:sup>+<\/jats:sup>stem cells rejuvenated cardiac tissue in aged mice. 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