Ginsenoside Rb1 attenuates arterial aging by reducing DNA damage in aged mice

OBJECTIVE: Vascular aging is a critical risk factor for the development and progression of cardiovascular diseases. Age-related degenerative changes in vascular structure and function significantly promote the onset of various vascular disorders. Currently, the specific molecular mechanisms underlying age-associated vascular structural and functional decline have not been fully elucidated. Ginsenoside Rb1 (Rb1), as the primary active component of ginseng, has been confirmed to possess potential anti-aging properties. This study aims to investigate the protective effects of Rb1 on the aorta in aged mice and its underlying molecular mechanisms, thereby providing experimental evidence and theoretical support for the screening of natural anti-vascular aging drugs. METHODS: Naturally aged (72-week-old) male C57BL/6J mice were randomly divided into two groups (n = 5 per group) to receive intraperitoneal injections of either PBS (Old group) or 20 mg/kg Rb1 (Old + Rb1 group) for 6 weeks. Young mice (12-week-old, n = 5) served as controls. Aortic tissues were analyzed using histomorphology (hematoxylin and eosin, H&E), nanoscale biomechanics (Atomic Force Microscopy, AFM), senescence biomarkers (p21 immunofluorescence, SA-β-gal staining), apoptosis (TUNEL assay), and DNA damage (γ-H2AX). RESULTS: Compared to the Old group, Rb1 significantly alleviated structural remodeling of the aging aorta, restoring smooth muscle cell alignment and extracellular matrix. AFM analysis showed that Rb1 ameliorated the aging-induced impairments in nanobiomechanical properties (including elasticity, viscosity, and surface topography) induced by aging. Furthermore, Rb1 treatment downregulated the expression of p21 in the aorta, reduced the positive area percentage of SA-β-gal positivity, and decreased the proportion of TUNEL-positive apoptotic cells, although none of these indicators were comparable to the levels observed in the Young control group. Notably, Rb1 significantly alleviates the elevation of γ-H2AX (a marker of DNA double-strand breaks) in the aging aorta. CONCLUSION: This study demonstrates that Rb1 attenuates DNA damage, thus ameliorating structural remodeling and biomechanical function of the aging aorta, and delaying vascular aging and apoptosis. Our findings suggest that Rb1 counteracts age-related aortic impairment, potentially by targeting the DNA damage pathway, which highlights its therapeutic potential against vascular aging.