UNIST Research Team Develops Technology for Selective Removal of Senescent Cells

A technology capable of selectively removing senescent cells has been developed, offering new prospects for the treatment of age-related diseases.

Professor Ja-Hyung Yu's team from the Department of Chemistry at UNIST and Professor Hye-Won Jeong's team from Konkuk University have developed a technology that forms artificial proteins inside the mitochondria of senescent cells to selectively eliminate them.

The developed technology can selectively target receptors overexpressed on the membranes of senescent cells, and it can also form artificial protein structures mediated by reactive oxygen species (ROS) that are expressed at higher levels compared to normal cells, enabling the selective removal of senescent cells without adversely affecting normal cells.

As humans age, normal cells have an increased likelihood of transforming into cancer cells, so cells spontaneously become senescent to prevent progression to cancer. However, the accumulation of senescent cells induces various inflammations and causes age-related diseases.

A schematic diagram illustrating research that targets mitochondria within senescent cells to induce apoptosis of senescent cells through self-assembled structures.

The research team studied methods to target senescent cells for the treatment of age-related diseases.

Carbon-based 'organic molecules' consist of parts capable of forming disulfide bonds and parts that can target senescent cells. Disulfide bonds are formed by the oxidation process between sulfur atoms, which can be promoted by substances such as reactive oxygen species.

Reactive oxygen species are byproducts generated during oxygen utilization, and mitochondria within senescent cells overexpress these reactive oxygen species. The overexpressed reactive oxygen species promote disulfide bond formation, leading to the creation of oligomers?small polymers formed by bonding molecules together.

The research team developed a technology to create artificial proteins with a helical structure called an 'alpha helix' on the surface through the self-assembly of oligomers. This structure strongly binds to the mitochondrial membrane, destroying the membrane and inducing cell apoptosis.

The team applied the developed technology to a mouse model with age-related dry macular degeneration and confirmed that senescent cells were efficiently removed and retinal tissue function returned to normal ranges. They also confirmed selective removal of senescent cells in the retinal tissue of naturally aged mouse models.

Professor Ja-Hyung Yu of the Department of Chemistry stated, "We confirmed in actual experimental mice that targeting the mitochondria of senescent cells induces dysfunction, leading to the selective removal of senescent cells," adding, "This approach differs from existing senolytic therapies and will present a new paradigm for treating age-related diseases."

Co-researcher and CEO Chaekyu Kim of Fusion Biotech said, "By targeting intracellular organelles, toxicity issues can be minimized and a wide therapeutic window can be secured," expressing expectations that "this will provide advantageous conditions for future preclinical and clinical trial designs."

This research was supported by the Mid-career Research Program and the Bio & Medical Technology Development Project of the National Research Foundation of Korea under the Ministry of Science and ICT, and was published online on September 4 in the Journal of the American Chemical Society, a prestigious journal of the American Chemical Society.

This content was produced with the assistance of AI translation services.