Development and Aging Program has the principal goal of bringing diverse research interests and expertise together and forging liaisons between basic scientists, clinicians, and translational research to build predictable models of embryonic development, organogenesis, organ function, aging and of disease-related processes.
The ultimate goal of this program is to understand how a functioning organ is formed and maintained in the organism, and how to correct or ameliorate a genetically or environmentally induced defect.
Program Director: Rolf Bodmer Ph.D. - Sanford Burnham Medical Research Institute
Marc Tatar - Brown University
Neal Silverman - University of Massachusetts Medical School
Paul Shaw - Washington University Medical School at St. Louis
Establish multiple models of functional aging in Drosophila melanogaster with high physiological relevance to human senescent phenotypes, specifically in the senescence of cardiac, immune and sleep functions.
Assess how insulin/IGF and TOR regulation of lifespan affects independent and conglomerate axes of functional aging.
Discover pathogenic mechanisms underlying age-dependent decline in cardiac, immune and sleep functions by methods of genetic manipulation including forward genetic screens and transgenic analysis of candidate factors.
Assess whether apparently divergent, asynchronous aspects of functional senescence are driven by a common process of aging.
Aging leads to degenerative change in multiple systems and cell types. These losses induce the functional decline of specific physiological systems that contribute to progressive morbidity and ultimately to death. Two fundamental questions for basic gerontology arise from these central observations. What are the processes of intrinsic physiological decline in structure and function that lead to the eventual expression of specific geriatric disorders? To what extent are different phenotypes of functional aging coordinately regulated by common factors of an underlying aging process? This program project will address these questions with integrated research on functional aging of a genetic model system, Drosophila melanogaster.
Human functional aging involves disorders of many body systems, including the cardiovascular, central and peripheral nervous, endocrine, hematopoetic-immune, musculoskelatal, reproductive, pulmonary and cutaneous systems. Understanding the genetic basis for variation in rates of decline in well-defined functions within these systems is an important goal of future geriatric research that holds promise with recent developments in human linkage and association studies. Aside from rodents, however, genetic models have rarely been used to understand specific pathogenic mechanisms of senescent phenotypes or to address fundamental questions of basic gerontology. We believe the time is right to now develop these approaches with Drosophila and then to use the fly’s strongest genetic asset — forward genetics, the mutant screen — to uncover basic pathogenic mechanisms of functional aging.