Preventing Senescence Associated Age- Related Diseases by Targeting Anti-apoptotic Proteins BCL-xL and BCL-2 Using ICM Molsoft

Isabel Molina & Dr. William Munroe


The accumulation of unhealthy cells in organisms that have entered cellular senescence, 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 onset of senescence and enhance the health of individuals. Senolytics, a group of drugs, have been recognized for their ability to promote apoptosis in senescent cells; by targeting anti apoptotic proteins. In this experiment the antiapoptotic proteins BCL-xL and BCL-2, found in both planaria and humans, were analyzed to determine if senolytic drugs ABT-737 and ABT-263 (Navitoclax) could inhibit these proteins; thus, inhibiting the anti-apoptotic mechanism of senescent cells. The inhibition of the anti-apoptotic mechanism of BCL-xl and BCL-2, is speculated to induce apoptosis of the senescent cells; therefore, eliminating them. The inhibition of planarian proteins BCL-xL and BCL-2, was analyzed in silico, and in vivo using whole cell proteomics. The Planmine protein sequence database and Dugesia japonica Nucleotide BLAST, from the U.S. National Library of Medicine, and the computer application Robetta, were utilized to create de novo planarian protein structures. The structures, created by Robetta, were used in computational protein-ligand 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 that Navitoclax can potentially bind to BCL-xL and BCL-2 proteins and remove senescent cells in planarian models.


Session 1

9:30am – 11:00am

Grand Salon

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