Background: The aorta functions as a pressure reservoir, essential for maintaining blood pressure that drives the cardiovascular system. To fulfil this role, the aorta is compliant, changing shape in response to changes in blood pressure. With age, compliance decreases due to increased wall stiffness, contributing significantly to cardiovascular disease risk. Vascular smooth muscle cells (VSMCs), the major cellular component of the aorta, respond by further decreasing aortic compliance. Once described as existing in two distinct states, quiescent or synthetic, VSMCs are now recognised as progenitor-like and can transition into diverse phenotypes. Despite much research into VSMC senescence, we lack an understanding of how VSMC phenotype changes across life course.

Methods: To better understand these transitions during ageing, we undertook a comparative analysis of published single-cell RNA sequencing (scRNA-seq) datasets from aortas across species. We developed a standardised cell classification approach based on shared marker gene sets, addressing inconsistencies in cell identity, abundance, and annotation. While gene-level overlap across datasets was poor, pathway-level analysis (GO/KEGG) revealed unique age-related VSMC metabolic rewiring signatures. In parallel, we have conducted scRNA seq of mouse aortae at young adult, middle-age and old-age to describe age-associated changes in VSMC genotype. This data confirmed the age-associated VSMC pathway-level signatures, suggesting that the VSMC ageing signatures are conserved across species. We are currently attempting to perform cross-species integration.