When Nature Meets Nurture: A Longevity Blueprint

Danielle Gutman ¹ Gabriel Lidzbarsky ¹ Dan Ben-Avraham ² Shai Carmi ³ Yun Freudenberg-Hua ^4,5 Freudenberg Jan ⁶ Ken Y. Hui ⁷ Ethen Kochav ³ Xinmin Liu ⁸ James Xue ³ Fillan Grady ³ Saurav Guha ^9,10,11 Ariel Darvasi ¹² Kenneth Offit ¹³ Laurie J. Ozelius ¹¹ Inga Peter ¹¹ Judy H. Cho ⁷ Harry Ostrer ¹⁴ Lorraine N. Clark ^8,15 Nir Barzilai ² Todd Lencz ^9,10 Peter Davies ⁴ Itsik Pe'er ^3,16 Gil Atzmon ¹

¹Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Israel
²Institute for Aging Research Departments of Medicine and Genetics, Albert Einstein College of Medicine, USA
³Department of Computer Science, Columbia University, USA
⁴The Litwin-Zucker Research Center for the Study of Alzheimer's Disease and Memory Disorders, The Feinstein Institute for Medical Research, USA
⁵Division of Geriatric Psychiatry, Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, USA
⁶Robert S. Boas Center for Genomics and Human Genetics, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, USA
⁷Department of Internal Medicine, Genetics & Pediatrics, Yale School of Medicine, USA
⁸Department of Pathology and Cell Biology, Columbia University Medical Center, USA
⁹Center for Psychiatric Neuroscience, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, USA
¹⁰Department of Psychiatry, Division of Research, The Zucker Hillside Hospital Division of the North Shore–long Island Jewish Health System, USA
¹¹Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, USA
¹²Department of Genetics, The Institute of Life Sciences, the Hebrew University of Jerusalem, Givat Ram, Israel
¹³Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, USA
¹⁴Department of Genetics and Pathology, Albert Einstein College of Medicine, USA
¹⁵Taub Institute for Research of Alzheimer’s Disease and the Aging Brain, Columbia University Medical Center, USA
¹⁶Center for Computational Biology and Bioinformatics, Columbia University, New York, Ny, USA

Medical advances and quality of life improvements have increased life expectancy leading to an increase in the aging population. Despite enormous research efforts, the aging phenotype remains elusive with a unique healthy aging model demonstrated by a group of people called centenarians, people who live over 100 years of age usually presenting intact cognition and minimal chronic conditions, often free of age-related diseases. For this reason, we chose to investigate a specific centenarian population – American Ashkenazi Jews, a homogeneous isolated population of Central- and Eastern-European and Middle Eastern ancestry. A cohort 150 centenarians and 150 unrelated controls with no familial history of longevity was sampled by Albert Einstein College of Medicine, all participants whole-genome sequenced and a structured filtration pipeline applied to obtain single nucleotide variations among the groups. Association analysis using Plink 1.9 software highlighted 50 age-associated loci, most of which are located at or near centromeric regions, or in gene deserts. Further bioinfomatic analysis is currently underway in order to characterize the effect of these loci on the healthy aging phenotype. Such characterization will enable implementation of animal models, such as C. elegans, of these loci and deeper understanding of their mechanism of action on both the cellular and organism levels.