Longevity, tumor, and physical vitality in rats consuming ginsenoside Rg1.

Background: Effects of the major ginsenoside Rg1 on mammalian longevity and physical vitality are rarely reported. Purpose: To examine longevity, tumor, and spontaneous locomotor activity in rats consuming Rg1. Methods: A total of 138 Wistar rats were randomized into 2 groups: control (N = 69) and Rg1 (N = 69). Rg1 (0.1 mg/kg per day) were orally supplemented from 6 months of age until natural death. Spontaneous mobility was measured by video-tracking together with body composition (dual energy x-ray absorptiometry) and inflammation markers at 5, 14, 21, and 28 months of age. Results: No significant differences in longevity (control: 706 days; Rg1: 651 days, p = 0.77) and tumor incidence (control: 19%; Rg1: 12%, p = 0.24) were observed between the two groups. Movement distance in the control group declined significantly by ∼60% at 21 months of age, together with decreased TNF-α (p = 0.01) and increased IL-10 (p = 0.02). However, the movement distance in the Rg1 group was maintained ∼50% above the control groups (p = 0.01) at 21 months of age with greater magnitudes of TNF-α decreases and IL-10 increases. Glucose, insulin, and body composition (bone, muscle and fat percentages) were similar for both groups during the entire observation period. Conclusion: The results of the study suggest a delay age-dependent decline in physical vitality during late life by lifelong Rg1 consumption. This improvement is associated with inflammatory modulation. Significant effects of Rg1 on longevity and tumorigenesis were not observed.

Reduced stem cell aging in exercised human skeletal muscle is enhanced by ginsenoside Rg1.

BACKGROUND: Stem cell aging, characterized by elevated p16INK4a expression, decreases cell repopulating and self-renewal abilities, which results in elevated inflammation and slow recovery against stress. METHODS: Biopsied muscles were analyzed at baseline and 24 h after squat exercise in 12 trained men (22 ± 2 y). Placebo (PLA) and immunostimulant Rg1 (5 mg) were supplemented 1 h before a squat exercise, using a double-blind counterbalanced crossover design. RESULTS: Perceived exertion at the end of resistance exercise session was significantly lowered after Rg1 supplementation. Exercise doubled endothelial progenitor cells (EPC) (p < 0.001) and decreased p16INK4a mRNA to 50% of baseline (d = 0.865, p < 0.05) in muscle tissues, despite p16INK4a+ cell and beta-galactosidase+ (ß-Gal+) cell counts being unaltered. Rg1 further lowered p16INK4a mRNA to 35% of baseline with greater effect size than the PLA level (d = 1.302, p < 0.01) and decreased myeloperoxidase (MPO) mRNA to 39% of baseline (p < 0.05). A strong correlation between MPO and p16INK4a expression in muscle tissues was observed (r = 0.84, p < 0.001). CONCLUSION: EPC in skeletal muscle doubled 1 d after an acute bout of resistance exercise. The exercised effects in lowering EPC aging and tissue inflammation were enhanced by immunostimulant Rg1, suggesting the involvement of immune stimulation on EPC rejuvenation.

Whole-life body composition trajectory and longevity: role of insulin.

The present study assessed the body composition trajectory of rats (N = 96) placed into 5 groups according to lifespan, using dual-energy x-ray absorptiometry every 6 months until end-of-life. A striking linearity between lifespan and bone mass percentage (not absolute bone mass) was observed. Long-lived rats show a higher bone mass percentage with a delayed insulin rise to a similar peak level as short-lived counterparts, followed by insulin declines and bone mass loss. Decreasing insulin after streptozotocin (STZ) injection caused a rapid bone mass loss (-10.5%) with a decreased 5-day survival rate to 35% in old rats (20 months). Insulin replacement to STZ-injected rats completely blocked bone mass loss and increased the survival rate to 71%. Normal old rats (20 months) had faster lean mass loss despite greater myofiber regeneration (centronucleation) compared with the young rats (4 months). Increased CD68+ and CD163+ cell infiltration into insulin-depleted muscle suggests a bone marrow cell exhaustion by aging muscle. Bone produces stem cells and phagocytes to continuously rejuvenate peripheral tissues. Our data suggests that aging and unsustainable life is associated with development of disproportionality between bone and the growing body size, partly due to insulin reversal from hyperinsulinemia during late life.