Ginsenoside Rg1 enhances stem cell abundance in aging human skeletal muscle after resistance exercise

Background: Ginsenoside Rg1 enhances senolytic effect of exercise in human skeletal muscle. Purpose: To determine the effects of Rg1 on stem cell enrichment and differentiation in skeletal muscle following resistance exercise in women over 60. Methods: In a randomized, double-blind, placebo-controlled crossover trial, 11 women (60-73 years) completed four sets of seated leg press (70% 1RM) 1 h after ingesting Placebo or Rg1 (10 mg). Muscle biopsies were assessed for activated mesenchymal stem cells (Stro-1+/Tom20high), neural progenitors (Nestin+), and vascular progenitors (CD34+/CD31+) at 0 h and 24 h post-exercise. Results: While exercise alone did not alter Stro-1+ cells and mitochondrial content (TOM20+) in muscle tissues, the high mitochondrial Stro-1+ cells was decreased by 45% (p < 0.05). Rg1 supplementation doubled high mitochondrial Stro-1+ cells and total mitochondrial content post-exercise (p < 0.05). Concentration gradient between the Stro-1+ cells and engaged myofibers is consistent with a potential mitochondrial delivery mechanism from bone marrow stem cells. Exercise reduced CD34+ cells (-68%, p < 0.05) and Nestin+ neural progenitors (-50%, p < 0.05), whereas Rg1 attenuated CD34+ cell depletion and increased Nestin+ neural progenitors by twofold (p < 0.05). Vascular endothelial progenitors (CD34+/CD31+) remained unchanged after exercise. Exercise decreased serum estradiol levels (-43%, p < 0.05), whereas Rg1 supplementation restored estradiol to pre-exercise levels and doubled progesterone concentrations. Conclusion: Rg1 supplementation prevents exercise-induced sex steroid depletion and markedly enhances stem cell abundance in skeletal muscle, which contributes to mitochondrial gains following resistance exercise in women over 60.