This is a revised application for a Mid-Career Investigator Award in Patient-Oriented Research (K24). The applicant, Dr. Thomas Perls, is an Associate Professor of Medicine and Geriatrics and Founder and Director of the New England Centenarian Study. Having received an NIH physician scientist award (K-12) and a Paul Beeson Faculty Scholar in Aging Research Award, Dr. Perls proceeded to become an independent scientist devoted to patient-oriented research. Specifically, through these earlier mentored awards, Dr. Perls developed expertise in conducting a population-based phenotypic study of an extremely old cohort. His independence is demonstrated by his receipt of four other NIH grants (RO-3, R-21 and two R0-1s). Dr. Perls has a substantial record of mentoring students and clinical investigators at various stages of their careers. He has mentored five American Federation of Aging Research Medical Student Geriatrics Scholars, three premedical and pre-graduate school students, two geriatrics fellows, a pre-doctoral fellow and an Assistant Professor in Geriatrics. All of these trainees successfully published papers with Dr. Perls. While carrying out the aims of his R01-funded study, a population-based bio-demographic study of centenarians and their families, this K24 grant provides that 15% effort will be devoted to gathering preliminary data and developing applications to fund a genetic epidemiological study of centenarians. Dr. Perls will attend courses in bioethics, responsible conduct of clinical investigations and genetic epidemiology as a part of his career development-related education goals. These centenarian studies provide fertile ground for mentees to gain hands-on experience in clinical research. Innumerable aspects of exceptional longevity are available for study from spirituality, personality, adaptive capacity and functional reserve, to demographic and clinical observations to epigenetic associations. 35% effort will be dedicated to mentoring established and future mentees. A large and diverse academic community with a broad spectrum of training programs will ensure an ample pool of highly qualified and talented mentees. Relevance to public health: The study of human exceptional longevity under Dr. Perls's mentorship, provides trainees, from students to junior faculty, fertile ground for studying a broad range of aspects of successful aging from religion, personality, adaptive capacity and functional reserve to environmental, behavioral and genetic associations with exceptional survival. Subsequent findings may ultimately translate into strategies that help people age more successfully.