Impact of aging on neck vasculature and brain biochemistry in female mice

Vollständiger Abstract

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Abstract Age‐related changes in large‐vessel biomechanics may contribute to neurovascular dysfunction and region‐specific biochemical remodeling in the brain, with important implications for female health. This study investigated the impact of aging on neck vasculature and brain lipid biochemistry in female C57BL/6NHsd mice by comparing young (12 weeks; n = 10) and middle‐aged (52 weeks; n = 10) cohorts using ultrasound imaging, histology, and mass spectrometry. In vivo ultrasound quantified carotid and jugular hemodynamics, including wall shear stress (WSS), circumferential cyclic strain (CCS), pulsatility index, and volumetric flow. Ex vivo assessments included spatial lipid mapping in vessels and brain, and histology staining to quantify elastin‐to‐collagen ratios. Middle‐aged females exhibited reduced carotid systolic velocity, systolic WSS, and body weight–normalized carotid volumetric flow compared to young controls, while pulsatility index and CCS showed non‐significant decreases. Histology revealed a reduction in the carotid elastin‐to‐collagen ratio, consistent with vascular remodeling. Lipidomic profiling identified age‐dependent shifts in lipid headgroups, including decreases across multiple brain lipid classes, increased N‐acylethanolamides, alongside increases in carotid cardiolipin and lysophosphatidylethanolamine. Hippocampal spectra showed clearer age‐related separation than whole‐brain analyses. Correlation analyses identified moderate to strong associations between vascular biomechanics and lipid features across tissues, supporting coordinated neurovascular and biochemical aging in female mice.