Humans vary widely in their age at death and health status over their life course. In addition, individuals appear to age at different rates. We consider the general hypothesis that a constellation of factors, both genetic and environmental in origin, affect the rate at which people age and their longevity. To test this hypothesis, we propose to measure biodemographic features of aging: exceptional longevity, slow reproductive senescence and their co-aggregation in extended families. Our data are obtained from a vast store of information on pedigrees from a large defined population. These data will help to identify families of interest on whom to measure epidemiologic, social, cognitive, physiological and molecular traits believed to be related to aging and longevity. We will examine associations among these characteristics in these families to better define an aging phenotype associated with exceptional longevity. We will genotype exceptionally long-lived individuals from these families, their offspring, and their nieces/nephews in an attempt to discover genes associated with a delayed aging phenotype. We adopt an interdisciplinary approach and use a large population setting to better understand the genetic and environmental bases for phenotypic variation in aging leading to exceptional longevity. We have four specific aims: (1) to combine excess longevity and reproductive senescence to model a familial Delayed Aging Phenotype; (2) to test the association between the familial Delayed Aging Phenotype and resistance to age-related chronic diseases and environmental stressors; (3) to conduct genetic linkage studies to identify linked markers and haplotypes associated with exceptional longevity; and (4) to assess whether offspring of long-lived parents have favorable measures of phenotypic traits that suggest an intermediate phenotype for slow aging. We will use the Utah Population Database that contains medical and demographic records on six million individuals merged into multi-generational families.
Aims associated with morbidity outcomes will be based on existing Utah Cancer Registry records and new links to Medicare records. This study will help to determine whether there are genetic variants associated with familial longevity and how such genes affect the risk of important traits and diseases associated with aging.
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