Senescence is a state in which cells under stress exit the proliferative cell cycle. Senescent cells accumulate in age-related lesions, and the elimination of senescent cells has been found to delay age-associated deterioration in animal models. To date, it has been difficult to identify compounds that inhibit senescence. Prior screens to find compounds that prevent senescence were based on expression of late-appearing, non-specific senescent markers, and often resulted in the development of agents that could increase cell proliferation.
MSK investigators have developed a highthroughput screen (HTS) to reveal novel compounds that block and/or inhibit senescence. They have discovered that the number of ATRX foci increases in cells undergoing senescence. This increase is robust and reproducible, and a common feature of cells undergoing senescence. The highthroughput screen utilizes ATRX foci as a screen for compounds with anti-senescent properties. In this screen, a decrease in the number of ATRX foci per cell (or a lack of increase) could indicate that a compound may be useful as a treatment for age-related conditions and diseases.
- HTS assay can be utilized to identify novel compounds involved in aging
- Ready-to-use research tools to evaluate in vitro and in vivo efficacy of hits and facilitate lead selection
Compounds that block or inhibit senescence could demonstrate wide clinical utility for a number of age-related conditions and diseases
PCT application PCT/US2015/056726 filed on October 21, 2015, and PCT application PCT/US16/034832 filed on May 27, 2016
Andrew Koff, PhD, Laboratory Head, Molecular Biology Program, Memorial Sloan Kettering