Transcriptome analysis of mouse aortae reveals multiple novel pathways regulated by aging

Area of Science:

• Cardiovascular Biology
• Aging Research
• Molecular Biology

Background:

• Vascular aging contributes to arterial dysfunction and age-related cardiovascular diseases.
• The molecular mechanisms of vascular aging remain incompletely understood.
• Understanding these mechanisms is crucial for developing interventions against vascular aging.

Purpose of the Study:

• To elucidate age-associated transcriptomic changes in mouse aortae.
• To identify key molecular pathways affected by arterial aging.
• To provide insights into strategies for mitigating vascular aging.

Main Methods:

• Bulk RNA sequencing of young and old mouse aortae.
• Analysis of transcriptomic data to identify differentially expressed pathways.
• Protein expression examination and smooth muscle cell (SMC) lineage tracing.

Main Results:

• Aged aortae showed upregulated immune response pathways (inflammation, apoptosis, phagocytosis).
• Extracellular matrix organization pathways were significantly downregulated in aged aortae.
• Downregulated pathways included protein folding control and stress response, with reduced heat shock protein (HSP) gene expression.
• Circadian core clock genes were differentially expressed between young and old aortae.
• SMCs in aged aortae maintained their differentiated phenotype.

Conclusions:

• Arterial aging in mice is characterized by a shift towards immune activation and a decline in extracellular matrix organization.
• Downregulation of stress response pathways and maintenance of SMC differentiation are key features of vascular aging.
• These findings offer critical insights for developing strategies to combat vascular aging and associated diseases.