Senescence Gene Expression Profiles and 90-Day Outcome in Stroke Patients

Area of Science:

• Gerontology
• Neurology
• Molecular Biology

Background:

• Cellular senescence is implicated in age-related vascular dysfunction and disease.
• The specific role of senescence in stroke patient outcomes remains unclear.
• Investigating senescence may reveal novel biological determinants of stroke recovery.

Purpose of the Study:

• To examine the association between senescence-associated gene expression and functional outcomes in acute ischemic stroke patients.
• To determine if senescence enrichment in blood cells correlates with stroke severity and recovery.

Main Methods:

• Recruited acute ischemic stroke patients and age/sex-matched controls.
• Measured whole-blood gene expression using microarrays.
• Quantified senescence enrichment via gene set enrichment analysis.
• Assessed functional outcome using the modified Rankin Scale (mRS) at 90 days.
• Analyzed relationships using ordinal logistic regression.

Main Results:

• Patients with poor stroke outcomes (mRS > 2) exhibited enriched senescence gene expression compared to those with good outcomes (mRS ≤ 2).
• High senescence levels were significantly associated with worse mRS scores (OR: 2.32), even after adjusting for age, sex, stroke severity, and diabetes.
• Key differentially expressed senescence-associated genes included EGFR ligands (amphiregulin, epiregulin) and C-C motif chemokine ligand 16.

Conclusions:

• Increased cellular senescence in blood is linked to worse functional outcomes after stroke.
• Blood cell senescence may contribute to vascular aging, inflammation, and blood-brain barrier disruption, impacting stroke recovery.
• Measuring senescence offers a potential biomarker for biological aging and predicting stroke outcomes.