Introductory Review on Sirtuins in Biology, Aging, and Disease

American biologist best known for his research on life span extension in the budding yeast Saccharomyces cerevisiae, round worms (Caenorhabditis elegans), and mice. He is currently a Novartis Professor of Biology at the Massachusetts Institute of Technology. Based on the discovery that SIR2 is a key regulator of longevity in both yeast and worms, he is interested in determining whether this highly conserved gene also governs longevity in other organisms, including mammals. In 1999, Guarente became co-founder of Elixir Pharmaceuticals, which aimed to develop drugs targeting sirtuin. Leonard Guarente wrote an autobiography in 2003 titled Ageless Quest: One Scientist's Search for Genes That Prolong Youth. He is founder of technology start-up Elysium Health. Raul Mostoslavsky received his M.D. from the University of Tucuman in Argentina and his Ph.D. from the Hebrew University in Jerusalem, Israel. His longstanding interest in basic science and epigenetics brought him to Harvard Medical School to pursue postdoctoral studies where he first became interested in sirtuins. In 2007 Dr. Mostoslavsky opened his own lab at the Massachusetts General Hospital Cancer Center, Harvard Medical School. He is currently the Laurel Schwartz Associate Professor of Oncology at the MGH Cancer Center, Harvard Medical School, the Kristin and Bob Higgins MGH Research Scholar, and an Associate Member of the Broad Institute. His main research interests are on the crosstalk between epigenetics and metabolism, and the roles of chromatin sirtuins in health and disease, particularly cancer. Aleksey Kazantsev received his bachelor's degree in biology and chemistry from Moscow Pedagogical University. As a graduate student he was enrolled in the Genetics, Molecular Biology and Biotechnology Program at the University of North Carolina at Chapel Hill and completed his PhD thesis in 1997. Dr. Kazantsev then joined David Housman's laboratory at the Massachusetts Institute of Technology, where he started work on cellular models of neurodegeneration. At MIT he developed a strong interest in drug discovery, and worked on the development of high-throughput drug screening assays. Through involvement in collaborative work with Genzyme Corporation, he became co-inventor on a few patent applications, disclosing novel neurodegenerative assays and therapeutic agents. He discovered an inhibitor of polyglutamine aggregation, which was neuroprotective in a Huntington’s disease mouse model, and published extensively in the field of Huntington’s disease and drug discovery. In 2002 Dr. Kazantsev was named assistant professor of neurology at Harvard Medical School and principal investigator at Massachusetts General Hospital, where he continued to pursue his interest in drug discovery for neurodegenerative diseases, setting up a high-throughput drug screening facility and in collaboration with other investigators performing drug screens targeting various neurodegenerative disorders. Currently he is a co-PI on a collaborative research project with Novartis toward the development of a cure for Huntington’ s disease.