Functional Genomics & Genome Maintenance in Aging

A host of questions are being explored in the realm of molecular genetics, from DNA damage and repair to the functional genomics of unknown SNPs conferring extreme human longevity. Substantial advances have been made using high-throughput genetic modalities available in the Department of Genetics. Initial data on animal and humans shows changes in methylation with aging that are tissue-specific and extend to animal and human models who develop age-related disease after intrauterine growth retardation, and in brains of both sick and healthy elderly subjects.

A cohort of offspring of centenarians and age-gender-matched controls will be followed prospectively, to determine the incidence of cardiovascular disease and cognitive impairment, pursuing investigation into favorable genotypes and their phenotypic expression. The primary goal of the project is to identify genes that contribute to exceptional longevity in humans and analyze associations of these genes with age-related diseases and longevity. The team is also identifying and examining new polymorphisms in major genes in the GH/IGF pathway and their relationship to GH/IGF levels, function, and age-related diseases.

Investigators in this area seek to unravel the mechanisms that underlie premature aging driven by DNA damage, investigate the relationship to normal aging, explore potential interventions, and translate findings of genome maintenance as a key factor in determining healthy life span in humans. Studies encompass the investigation of DNA damage-based mechanisms of premature or abnormal aging using mouse models as well as mouse and human cell cultures, and the development of new experimental interventions to slow this damage. Researchers are developing sets of blood-based biomarkers for premature aging in mice, which will be validated in normally aging mice and in a cohort of human subjects. The program also studies the role of genome maintenance as a pro-longevity system in humans by using genetic association and functional genomic analyses.