Age-Disturbed Vascular Extracellular Matrix Links to Abdominal Aortic Aneurysms

Area of Science:

• Vascular Biology
• Genomics
• Aging Research

Background:

• Abdominal aortic aneurysm (AAA) is a prevalent, life-threatening vascular condition disproportionately affecting older men.
• The specific mechanisms driving the age-related increase in AAA incidence and mortality are not fully understood.

Purpose of the Study:

• To identify age-associated transcriptional changes in the aorta across species.
• To elucidate the biological processes and signaling pathways involved in aortic aging.
• To uncover the relationship between aortic aging signatures and genes implicated in AAA.

Main Methods:

• RNA sequencing (RNA-seq) of mouse aortas from young and old males.
• Integration of mouse RNA-seq data with human aortic gene expression datasets (GTEx) and AAA-specific datasets (GSE183464).
• Validation of key findings using an angiotensin II-induced mouse model of AAA.

Main Results:

• Identified 1,001 age-shifted genes common to both mouse and human aortas.
• Age-increased genes were predominantly intracellular, linked to mitochondrial function and translation.
• Age-decreased genes were extracellular, associated with extracellular matrix (ECM) organization; these overlapped with known AAA genes.

Conclusions:

• A conserved transcriptional signature characterizes aortic aging.
• Mitochondrial dysfunction and imbalanced ribosomal homeostasis are likely drivers of aortic aging.
• Age-related alterations in the ECM create a substrate conducive to abdominal aortic aneurysm development.