Vascular function in the aging human brain during muscle exertion.

To determine how brain oxygenation is stably maintained during advancing age, cerebral oxygenation and hemoglobin were measured real-time at 10 Hz using near-infrared spectroscopy (NIRS) at rest (30 seconds) and during a 10-repeated handgrip strength test (30 seconds) for 834 adults (M/F = 45/55%) aged 20-88 y. The amplitude of cerebral hemodynamic fluctuation was reflected by converting 300 values of % oxygen saturation and hemoglobin of each 30-second phase to standard deviation as indicatives of brain oxygenation variability (BOV) and brain hemodynamic variability (BHV) for each participant. Both BOV (+21-72%) and BHV (+94-158%) increased during the maximal voluntary muscle exertions for all age levels (α < 0.05), suggesting an increased vascular recruitment to maintain oxygen homeostasis in the brain. Intriguingly, BHV was >100 folds for both resting and challenged conditions (α < 0.001) in >80% of adults aged above 50 y despite similar BOV compared with young age counterparts, indicating a huge cost of amplifying hemodynamic oscillation to maintain a stable oxygenation in the aging brain. Since vascular endothelial cells are short-lived, our results implicate a hemodynamic compensation to emergence of daily deficits in replacing senescent endothelial cells after age 50 y.

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.

Aerobic exercise induces tumor suppressor p16INK4a expression of endothelial progenitor cells in human skeletal muscle.

Aerobic exercise induces oxidative stress and DNA damage, nevertheless, lowers cancer incidence. It remains unclear how genetic stability is maintained under this condition. Here, we examined the dynamic change of the tumor suppressor p16INK4a in cells of skeletal muscle among young men following 60-min of aerobic cycling at 70% maximal oxygen consumption (V̇O2max). Rg1 (5 mg, an immunostimulant ginsenoside) and placebo (PLA) were supplemented 1 h before exercise. Data from serial muscle biopsies shows unchanged p16INK4a+ cells after exercise followed by a considerable increase (+21-fold) in vastus lateralis muscle 3 h later. This increase was due to the accumulation of endothelial progenitor cells (p16INK4a+/CD34+) surrounding myofibers and other infiltrated nucleated cells (p16INK4a+/CD34-) in necrotic myofibers. During the Rg1 trial, acute increases of p16INK4a+ cells in the muscle occurred immediately after exercise (+3-fold) and reversed near baseline 3 h later. Rg1 also lowered IL-10 mRNA relative to PLA 3 h after exercise. Post-exercise increases in VEGF mRNA and CD163+ macrophages were similar for PLA and Rg1 trials. Conclusion: The marked increases in p16INK4a protein expression of endothelial progenitor cells in skeletal muscle implicates a protective mechanism for maintaining genetic stability against aerobic exercise. Rg1 accelerates resolution of the exercise-induced stress response.