Assessment of the Capability of Mesenchymal Stem Cells and/or Pyrroloquinoline Quinone in Compensating the Age-related Dysfunctions of AMP-Activated Protein Kinase Pathway in Wistar Rats

Aging is characterized by a decline in physiological functions and an increased susceptibility to age-related diseases. This study investigates the therapeutic potential of mesenchymal stem cells (MSCs) and pyrroloquinoline quinone (PQQ), individually and in combination, to counteract aging-related physiological declines, with a specific focus on their modulation of the AMP-activated protein kinase (AMPK) pathway, a key regulator of cellular energy homeostasis and stress response. Aging was induced in thirty-seven female rats using D-galactose, simulating the metabolic imbalances and oxidative stress characteristic of aging. The experimental groups included controls, aged rats without treatment, and aged rats treated with MSCs, PQQ, or a combined MSC-PQQ regimen. MSC homing analyses and Behavioral assessments, oxidative stress assays, gene expression profiling, histopathological evaluations were conducted to provide a multidimensional view of treatment efficacy. MSC homing confirmed successful tissue localization and repair, underscoring the regenerative capacity of MSCs. Remarkably, the combined MSC-PQQ therapy (APQQST) markedly improved anxiety-related behaviors, evidenced by increased rearing and grooming activities (p < 0.01). Oxidative stress biomarkers supported these findings; treated groups exhibited significantly reduced malondialdehyde (MDA) levels and elevated antioxidant defenses, including glutathione (GSH) and glutathione peroxidase (GPX) (p < 0.01). Gene expression analysis highlighted the beneficial upregulation of key genes such as LKB1, PFKFB3, TSC2, and HMGR, crucial for cellular energy homeostasis and stress response, with the combination therapy showing the most pronounced effects. Furthermore, histopathological assessments underscored significant liver tissue recovery in treated groups, particularly with combined treatment (APQQST), with minimal vacuolar degeneration and restored hepatic architecture (p < 0.01). These findings highlight the synergistic effects of MSCs and PQQ in mitigating behavioral, molecular, and physiological aspects of aging, underscoring their potential as promising therapeutic agents for promoting healthy aging and offering a foundation for future translational research and clinical applications.