Cardiosphere-derived cells (CDCs) from young animals can rejuvenate old animals. New research shows that intracardiac injection of neonatal rat CDCs in old rats improves heart function (reducing cardiac stiffness, hypertrophy, fibrosis, and diastolic dysfunction), increases exercise capacity by ∼20%, and improves the levels of systemic biomarkers compared with vehicle injection. CDC therapy also induced a change in cardiac gene expression towards a youthful pattern, and telomeres of heart cells from CDC-treated animals were longer than vehicle-treated animals. In vitro studies with human heart progenitors from old donors (aged >55 years) exposed to human CDCs or exosomes secreted by CDCs from young donors (aged <2 years) showed that young CDCs secrete exosomes that increase telomerase activity and telomere length, and reduce the number of senescent human heart cells.