The Genetic Basis of a Disease Free Model of Aging

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DESCRIPTION (provided by applicant): Information is limited about the genetic factors participating in or mediating the pace of aging in humans. Such information would be valuable to our understanding of the biology of individual variation in the aging process, which could help us understand the mechanisms of longevity and have an impact on improving the health span of individuals. A significant problem in this regard is the lack of adequate disease independent biomarkers of aging to define as phenotypes. The aims of this exploratory project will assess the feasibility of utilizing the normal decline in lens transparency as a disease independent model of aging from the perspective of a genetic based study. The aims of this exploratory assessment will establish the feasibility, rationale, and research design details that v/ill be utilized to inform the basis for a line of investigation that will involve identifying gene(s) and gene-environment interactions that participate in the aging process and rate of the aging process in humans using a disease independent model of aging. To accomplish the goals of this exploratory project, quantitative lens transparency measurements, health, exposure and demographic data, and DMA will be collected from multigenerational families. The proband for each family will be recruited from an ongoing population based study, the Cardiovascular Health Study (CHS), which is a population based longitudinal study being conducted in adults aged 65 and older. Preliminary data from active CHS participants indicates that they are willing to contact their family members to participate in a study involving the genetics of aging, the majority have family structures that will be conducive to conducting this exploratory study, and that approximately half of the active participants will have both of their original lens intact and available for measurement. This is the first study to propose to use lens transparency as a continuous, quantitative measure of the human aging process that will be suitable for genetic linkage and gene identification.