Research on the Function and Mechanism of the Medicinal Food Synergistic Formula Shenqi Paste in Enhancing Senescence Decline via PI3K-Akt/Nrf2/PINK1 Cooperative Regulation of Mitochondrial Autophagy

BackgroundFrailty in the elderly is a state of reduced physiological reserve and weakened stress resistance, severely affecting quality of life and increasing healthcare burdens. Currently, effective treatments are lacking, while Traditional Chinese Medicine, especially "medicinal food homology" formulas, shows potential in improving frailty. Shenqi Paste, composed of Astragalus, Codonopsis, and other medicinal food homology ingredients, has the effects of reinforcing the spleen and kidney and supplementing qi and blood, but its specific molecular mechanisms in improving frailty remain unclear. Recent studies highlight the role of mitophagy in aging, with PI3K-Akt, Nrf2, and PINK1 signaling pathways potentially involved in coordinated regulation of mitochondrial function.Research ObjectivesThis study aims to determine whether Shenqi Paste enhances mitophagy through coordinated regulation of the PI3K-Akt/Nrf2/PINK1 signaling pathways, thereby ameliorating frailty in aging, and to systematically elucidate its mechanisms at animal, tissue, and molecular levels.HypothesisShenqi Paste activates the PI3K-Akt/Nrf2/PINK1 signaling axis through multi-component synergy, enhances mitophagy, restores mitochondrial function, and thereby improves frailty-related muscle dysfunction and systemic metabolic disturbances.MethodsEstablish an aged frailty rat model and randomly assign groups: control, Shenqi Paste (high, medium, low doses), and groups with pathway inhibitors (PI3K-Akt, Nrf2, or PINK1 inhibitors) combined with Shenqi Paste.Evaluate the overall improvement of frailty by measuring body weight, grip strength, treadmill performance, and frailty index scores.Detect protein and gene expression of PI3K, Akt, Nrf2, PINK1, Parkin, LC3-Ⅱ/Ⅰ, and p62 in gastrocnemius muscle using Western Blot and RT-PCR.Observe colocalization of mitochondria and autophagosomes via immunofluorescence.Analyze changes in serum frailty-related biomarkers using metabolomics.