Single-nucleus transcriptomics reveals a gatekeeper role for FOXP1 in primate cardiac aging

Area of Science:

• Cardiovascular Biology
• Aging Research
• Molecular Cardiology

Background:

• Aging is a primary risk factor for cardiovascular diseases.
• Cellular mechanisms of cardiac aging remain incompletely understood.
• Understanding cell-specific changes is crucial for targeting age-related heart conditions.

Purpose of the Study:

• To define cell composition and transcriptomic changes in the aging primate heart.
• To identify key molecular drivers of cardiac aging at single-cell resolution.
• To explore potential therapeutic targets for age-related cardiac dysfunction.

Main Methods:

• Single-nucleus RNA sequencing of left ventricles from young and aged cynomolgus monkeys.
• Analysis of cell type composition and differential gene expression.
• Transcription regulatory network analysis to identify key factors.

Main Results:

• Aged cardiomyocytes showed significant cell number reduction and transcriptional dysregulation.
• FOXP1, a critical transcription factor, was found to be downregulated in aged cardiomyocytes.
• FOXP1 target genes involved in heart function and disease were dysregulated.
• FOXP1 deficiency induced hypertrophic and senescent phenotypes in human cardiomyocytes.

Conclusions:

• This study provides a single-cell resolution map of cardiac aging in primates.
• Downregulated FOXP1 is identified as a key driver of cardiac aging and associated diseases.
• FOXP1 represents a potential therapeutic target for interventions against cardiac aging.