Model Systems for Cellular Senescence

This project aims to develop a novel in vivo model system to discover tissue-specific and common biomarkers of cellular senescence, with the ultimate goal of enabling targeted therapeutic interventions such as CAR-T cell therapy. The accumulation of senescent cells plays a pivotal role in aging and age-related diseases. While removing senescent cells has shown promising results in delaying aging in preclinical models, clinical applications of senolytic therapies remain limited. New, reliable biomarkers are urgently needed to improve the selectivity and efficacy of such therapies.

To address this gap, we propose using polyethersulfone hollow fiber encapsulation technology to implant primary progenitor cells into murine models. This encapsulation isolates the cells from the host immune system while preserving exposure to the host's systemic environment. By implanting these encapsulated cells into both young (20-year human equivalent) and aged (70-year equivalent) mice, we will study how systemic aging influences senescence at the molecular level. High-throughput RNA sequencing and proteomics will be employed to uncover gene and protein expression patterns unique to senescent or pre-senescent cells within specific tissue contexts.

This platform is uniquely positioned to identify pre-senescent biomarkers—molecular signatures that emerge early in the transition to full cellular senescence—thus offering potential targets for early therapeutic intervention. In addition, the encapsulated system provides a scalable and reproducible platform for screening anti-aging compounds, understanding age-related signaling environments, and identifying humoral factors driving cellular aging. Significance and Expected Impact:

1. Innovation in Model Systems: Establishes a robust, non-invasive model system to study cellular senescence and test therapeutics without direct immune interaction.

2. Biomarker Discovery: Enables the identification of novel and tissue-specific biomarkers for senescent and pre-senescent cells, expanding therapeutic targets for CAR-T and senolytic therapies.

3. Therapeutic Applications: Supports the development of selective, precision-based anti-aging interventions.

4. Research Infrastructure: Provides a valuable tool for Saudi researchers working in aging biology, cellular therapy, and regenerative medicine.

5. Translational Potential: Bridges basic biology with clinical application, supporting Saudi Vision 2030 through advanced biotechnological innovation.