Age-Associated Changes in Endothelial Transcriptome and Epigenetic Landscapes Correlate With Elevated Risk of...

Area of Science:

• Neuroscience
• Vascular Biology
• Aging Research

Background:

• Stroke is a major cause of death and disability, with incidence increasing with age.
• Mechanisms of age-related blood-brain barrier (BBB) dysfunction and stroke remain poorly understood.
• Cerebral endothelial cells (ECs) form the BBB, maintaining vascular integrity through cellular junctions.

Purpose of the Study:

• To investigate age-associated changes in cerebral endothelial cells.
• To identify molecular mechanisms underlying age-related BBB dysfunction.
• To explore the role of the apelinergic system in vascular health and aging.

Main Methods:

• Analysis of intracerebral bleeding incidence in aging mice.
• Isolation and gene expression profiling of cerebral ECs across different ages (2-24 months).
• Investigation of age-dependent changes in DNA methylation and chromatin accessibility in ECs.

Main Results:

• Intracerebral bleeding incidents increase with age in mice.
• Significant age-dependent dysregulation of 1388 genes, including those crucial for BBB maintenance.
• Correlations observed between age-related chromatin structure changes and gene expression.
• Age-dependent downregulation of the Aplnr gene and reduced promoter chromatin accessibility.

Conclusions:

• The Aplnr gene, associated with vasodilation and vascular health, is downregulated with age in cerebral ECs.
• Age-dependent changes in chromatin accessibility correlate with gene expression dysregulation.
• The apelinergic axis (apelin ligand and receptor) may play a critical role in maintaining BBB integrity and vascular health during aging.