Age-Disturbed Vascular Extracellular Matrix Links to Abdominal Aortic Aneurysms

• Published in: The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2024-11, Vol.79 (11)
• Main Authors: Yu, Zhenping, Wu, Andong, Ke, Hao, Liu, Jiankun, Zhao, Ya, Zhu, Yuanzheng, Wang, Xiao-Yu, Xiang, Yang, Xin, Hong-Bo, Tian, Xiao-Li
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aging - genetics; Angiotensin II - pharmacology; Animals; Aorta, Abdominal - metabolism; Aorta, Abdominal - pathology; Aortic Aneurysm, Abdominal - chemically induced; Aortic Aneurysm, Abdominal - genetics; Aortic Aneurysm, Abdominal - metabolism; Aortic Aneurysm, Abdominal - pathology; Disease Models, Animal; Extracellular Matrix - metabolism; Humans; Male; Mice; Middle Aged
• ISSN: 1079-5006; 1758-535X; 1758-535X
• DOI: 10.1093/gerona/glae201

Abstract Abdominal aortic aneurysm (AAA) is a common but life-threatening vascular condition in men at an advanced age. However, the underlying mechanisms of age-increased incidence and mortality of AAA remain elusive. Here, we performed RNA sequencing (RNA-seq) of mouse aortas from males (young: 3-month, n = 4 vs old: 23-month, n = 4) and integrated with the data sets of human aortas (young: 20–39, n = 47 vs old: 60–79 years, n = 92) from GTEx project and the data set (GSE183464) for AAA to search for age-shifted aortic aneurysm genes, their relevant biological processes, and signaling pathways. Angiotensin II-induced AAA in mice was used to verify the critical findings. We found 1 001 genes transcriptionally changed with ages in both mouse and human. Most age-increased genes were enriched intracellularly and the relevant biological processes included mitochondrial function and translational controls, whereas the age-decreased genes were largely localized in extracellular regions and cell periphery and the involved biological processes were associated with extracellular matrix (ECM). Fifty-one were known genes for AAA and found dominantly in extracellular region. The common age-shifted vascular genes and known aortic aneurysm genes had shared functional influences on ECM organization, apoptosis, and angiogenesis. Aorta with angiotensin II-induced AAA exhibited similar phenotypic changes in ECM to that in old mice. Together, we present a conserved transcriptional signature for aortic aging and provide evidence that mitochondrial dysfunction and the imbalanced ribosomal homeostasis act likely as driven-forces for aortic aging and age-disturbed ECM is the substrate for developing AAA.