PICLS with human cells is the first high throughput screening method for identifying novel compounds that extend...

Area of Science:

• Gerontology
• Cell Biology
• Drug Discovery

Background:

• Age-related diseases pose a significant challenge, impacting healthspan and lifespan.
• Anti-aging interventions are crucial for addressing these diseases.
• Developing efficient methods to assay cellular aging is essential for drug screening.

Purpose of the Study:

• To present two novel, cost-effective methods for assaying chronological lifespan in human cells.
• To enable quantitative assessment of cell survival and death for anti-aging research.
• To validate these methods using known anti-aging compounds and screen for new longevity-extending drugs.

Main Methods:

• A modified classical outgrowth assay with quantitative assessment of surviving cells.
• A propidium iodide fluorescent-based measurement of cell death (PICLS) assay for high-throughput screening.
• Validation using 2,5-anhydro-D-mannitol and rapamycin, followed by screening of 162 chemical entities.

Main Results:

• Both developed methods are fast, simple, cost-effective, and yield quantitative data.
• The outgrowth assay is suitable for validating post-intervention reproductive potential.
• The PICLS method demonstrated high-throughput screening potential, identifying three novel compounds that extend human cell longevity.

Conclusions:

• The presented assays provide valuable tools for gerontology research and anti-aging drug discovery.
• These methods facilitate the identification of compounds that can extend human cell lifespan.
• The findings contribute to the goal of closing the gap between lifespan and healthspan.