With the increasing size of the aging population in the United States, we anticipate a surge of patients with late-onset neurodegenerative disorders, including dementias of the Alzheimer type (AD), various forms of Parkinson disease (PD), multi-infarct, fronto- temporal, Lewy body, Huntington (HD) and subcortical dementias, and various forms of ataxia. All of these disorders appear to involve genome alterations and DNA repair capacity in cells, and they are coupled to the biology of the aging brain in ways that remain unclear. We propose a meeting that integrates basic processes of aging with those of DNA repair, genomic instability, and clinical aspects of neurological and neurodegenerative disease. The program is designed to bring together three groups of leading scientists with interests in aging, DNA repair, and neurodegeneration. Merging of these fields is intended to develop new insights into in how normal processes of aging contribute to the development of late-onset disease. There is no existing meeting that integrates advances in all three fields. Thus, the proposed meeting breaks new ground. For most neuroscientists, neurological abnormalities have been considered primarily in light of protein-mediated toxicity. However, emerging data implicate both age-dependent alterations in DNA repair capacity and strand breaks as key factors relevant to late onset disease such as AD, PD, and HD. The theme of DNA repair and genomic instability has been typically discussed at meetings as it relates to cycling cells and cancer. It has become clear, however, that impact of accumulating lesions in DNA is different in terminally differentiated cell such as neurons, and changes with age. Relatively little is known about the mechanisms. The meeting focuses on current and emerging topics: relevant to how lesion repair changes normally in aging neurons, and (2) how alterations in DNA repair and genomic instability might contribute to late onset of neurodegenerative disease. We are committed to supporting young scientists and encouraging intellectual dialogue, the sharing of ideas, and discussion of current emerging issues with established experts. Project Narrative With the increasing size of the aging population in the United States, we anticipate a surge of patients with late-onset neurodegenerative disorders. All of these disorders appear to involve genome alterations and DNA repair capacity in cells, and they are coupled to the biology of the aging brain in ways that remain unclear. We propose the Second Genome Dynamics Neuroscience Meeting (GDN II) that integrates basic processes of aging with those of DNA repair, genomic instability, and clinical aspects of neurological and neurodegenerative disease. The program is designed to bring together three groups of leading scientists: (1) those with a primary interest in basic mechanisms of aging in the brain, and (2) those with primary interests in DNA lesions and their repair, and (3) those with interests in specific neurodegenerative diseases. Merging of these fields is intended to develop new insights into how normal processes of aging contribute to the development of late-onset disease. ? ? ? ? ?
