This is a revised competing renewal application for the Cardiovascular Health Study (CHS) All Stars Study, which was established to evaluate exceptional survival.
The aims of this continuation proposal break new ground in evaluating longevity in a prospective cohort and studying age-related changes across systems. Continued follow-up of the 1066 survivors, median age 89 (range 81-100+), will allow us to better characterize exceptional survival, including longevity to age 90. In addition to continuing to follow the cohort for longevity and function, we want to further our efforts to study age related changes longitudinally across multiple physiologic systems. Exceptional survival and longevity would require slow aging across systems. However, we do not know if older adults who maintain health in one system are more likely to maintain health in other systems. We will determine if a longitudinal, multisystem index more precisely predicts mortality in older adults compared to age or a previous cross-sectional index. Leveraging a recently funded genome-wide association study (GWAS) in CHS (Psaty R01 HL087652) for CVD outcomes, we will also contribute to the evaluation of the genetic underpinnings of exceptional survival phenotypes.
The specific aims are: 1) To continue to follow the CHS All Stars cohort to characterize their longevity, physical and cognitive function, and changes in markers of aging including adrenal androgens, insulin/growth hormone axis and inflammatory markers. 2) To examine clustering of longitudinal 'minimal aging' in CHS across multiple candidate systems, including vascular (carotid wall thickness), brain (cognition), kidney (creatinine), pulmonary (forced vital capacity), metabolic ( fasting glucose), musculoskeletal (grip strength) systems and to rank individuals with the least to greatest multisystem aging. 3) Using a genome wide association approach, to determine whether there are novel genetic variants related to longevity, disease and disability-free survival and multisystem minimal aging in CHARGE consortium cohorts. The CHS cohort is well positioned to characterize the epidemiology of exceptional survival. This competing renewal will continue with a collaborative tradition that encourages broad use of the CHS and the CHS All Stars data.
Improving the quality of added years of life is an important goal of research in aging and geriatrics. This research focuses on defining multisystem aging changes and identifying predictors of very long term function that can be targeted to improve active life expectancy. The findings of this work will have a tremendous impact on improving our understanding of the aging process and identifying targets for intervention.
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