Decoding the Spatiotemporal Logic of Cellular Senescence through Multimodal Exosomal miRNA Integration

Area of Science:

• Biomedical Engineering
• Molecular Biology
• Gerontology

Background:

• Exosomal RNAs are crucial biomarkers for cellular communication and disease progression.
• Current methods for exosomal RNA analysis often require cell lysis, limiting in situ monitoring.
• Understanding dynamic RNA changes in aging and neurodegenerative diseases like Alzheimer's is critical.

Purpose of the Study:

• To develop a multimodal biosensing platform for in situ, label-free monitoring of exosomal RNAs.
• To create a comprehensive RNA dynamic map during oxidative stress-induced cellular senescence.
• To validate the platform for staging Alzheimer's disease (AD) and identifying diagnostic biomarkers.

Main Methods:

• A cascade biosensing system integrating aptamer recognition, rolling circle amplification (RCA), and G-quadruplex/hemin signal transduction.
• Electrochemical and colorimetric signal integration using an inverse-variance-weighted data fusion algorithm.
• Application to oxidative stress models and clinical samples from Alzheimer's disease patients.

Main Results:

• Ultrasensitive and precise detection of exosomal RNAs without cell lysis.
• Construction of a time-resolved RNA dynamic map during cellular senescence, revealing distinct miRNA roles (miRNA-21, miRNA-29c, miRNA-34a).
• Successful staging of Alzheimer's disease (mild cognitive impairment vs. progressive AD) and identification of exosomal miRNA-21 and miRNA-34a as independent risk factors.

Conclusions:

• The developed amplified, multimodal biosensing framework enables robust profiling of exosomal RNA communication.
• This platform offers a powerful tool for stage-resolved biomolecular mapping in precision geroscience and diagnostics.
• Exosomal miRNA signatures provide a robust molecular basis for precision diagnostics in aging and Alzheimer's disease.