Recent results of centenarian pedigree and genetic studies suggest that further genetic studies could lead to helpful discoveries of genetic variations that significantly impact upon the ability to achieve exceptional old age. Such variations are hypothesized to affect the rate of aging and susceptibility to various age-associated diseases that cause """"""""premature"""""""" mortality. Association studies in particular must be ethnicity-specific and thus it is important that when significant associations are observed, similar studies should be performed with sample sets that differ according to ethnicity. Genetic variations that remain significant across ethnic lines would be particularly robust and of particular interest. These variations, in turn, could lead to the discovery of important drug targets for the intervention of age-associated diseases. The island prefecture (state) of Okinawa, Japan forms a potentially important area to search for genetic variations that may influence the aging process since they have been the longest-lived of the Japanese since life expectancy records have been calculated in the 1920s. Okinawa is also the base for the longest-running centenarian study in the world. Age-verification documents exist (koseki system) that date back to 1879. International comparisons show that Okinawa has what may be the highest documented life expectancy for a country or state at 81.2 years and among the world' s highest documented prevalence of centenarians, at 33.6 per 100,000 (versus 10 per 100,000 in the US.). The high centenarian prevalence exists despite outmigration of this birth cohort and a relatively high birthrate in subsequent generations. Moreover, if Okinawans emigrate to other locales and are exposed to similar environmental hazards (e.g. Hawaii), they remain the longest-lived of the Japanese. Thus, Okinawan-Japanese present an excellent population for determining genetic determinants of aging and potential resistance to the chronic diseases of aging. Okinawan centenarians, in particular, are most likely to possess genes that confer a survival advantage. Therefore, in concert with the New England Centenarian Study, we propose enrolling Okinawan-Japanese centenarians and controls to pursue the following specific aims:
Specific Aim 1 : To enroll 200 Okinawan centenarians and 200 controls for abbreviated phenotypic characterization, bank their DNA and establish lymphoblast cell lines.
Specific Aim 2 : To explore the utility of specific single nucleotide polymorphisms (SNPs) of selected candidate genes or groups of SNPs (""""""""haplotype blocks"""""""") in differentiating between centenarians and controls in the New England Centenarian and Okinawan Centenarian samples.
