Preventing Senescence Associated Age-Related Diseases by Targeting the Anti-Apoptotic Proteins BCL-xL and BCL-2

Isabel Molina, Yareli Moreno and Dr. William Munroe


The accumulation of unhealthy cells in organisms that have entered cellular senescence, which is irreversible, have been known to cause many age-related diseases; due to their anti-apoptotic properties. As aging increases an individual’s risk of developing chronic diseases, it is possible that targeting aging by regulating senescence pathways can delay the onstart of senescence and enhance the health of individuals. A group of drugs known as senolytics drugs have been recognized for their ability to promote apoptosis in senescent cells by targeting anti apoptotic proteins. In this experiment, the BCL-xL and BCL-2 anti-apoptotic proteins, found in both planaria and humans, were analyzed to determine if senolytic drugs ABT-737 and ABT-263 could interact and inhibit their anti-apoptotic mechanisms to induce apoptosis of the senescent cells. Planarian proteins BCL-xL and BCL-2, will be analyzed in silico and in vivo. The Planmine protein sequence database, along with computer application Robetta will be used in the creation of de novo planarian protein structures for use in protein-ligand docking computational simulations using ICM Molsoft. ABT-737 in complex with planarian BCL-xL did not yield favorable binding energy values in kcal/mol; thus, ABT-737 unsuccessfully bound with planarian BCL-xL. However, ABT-263 yielded negative binding energy values in kcal/mol; thus, ABT-263 bound successfully to planarian BCL-xL and BCL-2. These findings indicate Navitoclax has the ability to bind to BCL-xL and BCL-2 proteins and remove senescent cells in planarian models.