7. Project Abstract The Kuakini Medical Center (Kuakini) Hawaii Healthspan Study will focus a multidisciplinary team of genetic, epidemiological, and geriatric scientists on the use of innovative approaches for secondary data analysis. We will use existing human data and specimens from the 45-year Kuakini Honolulu Heart Program /Honolulu Asia Aging Study, longitudinal studies of aging and chronic diseases in Japanese-American men. Our work will focus on functional characteristics of healthy aging over the lifespan ("healthspan") and will attempt to identify genetic factors that help people survive to older ages in good health. While terms such as "successful", "healthy" or "effective" aging describe a paradigm of aging with minimal chronic disease, the functional (physical and cognitive), characteristics of such aging are poorly understood and little is known about genetic or environmental predictors. In recent work we have 1) Operationalized phenotypes of healthy aging that use performance-based measures of function 2) Identified environmental predictors of healthy aging and longevity in a longitudinal study, 3) Found a gene (FOXO3A) with variants strongly associated with healthy aging and longevity;4) Replicated the CETP gene association with longevity and extended the finding to healthy aging. For the current study, we propose to: 1) IDENTIFY additional genes associated with longevity using a two stage nested case-control study of candidate genes from energy sensing pathways and sequencing around areas of interest;2) CONDUCT a prospective study of genetic predictors of survival and healthy survival;3) CONDUCT a prospective study of genetic predictors of rate of change in major aging related traits. Discovery of biologic pathways that affect vulnerability to disease and disability could have a dramatic impact on our ability to achieve healthy old age by identifying biological targets for new therapies. Our study directly supports NIA's mission to improve the health and well-being of older Americans.

Public Health Relevance

The Kuakini Medical Center (Kuakini) Hawaii Healthspan Study will investigate how people's genes affect their ability to achieve healthy old age. This study focuses on understanding physical and cognitive function over the lifespan and identifies genetic and environmental factors that enable people to survive to exceptional ages in good health. Research on factors that lead to healthy aging may help us develop therapies that result in less age-related disease and disability and increase quality of life at older ages.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG038707-02
Application #
8332827
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Rossi, Winifred K
Project Start
2011-09-15
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$287,000
Indirect Cost
$82,000
Name
Kuakini Medical Center
Department
Type
DUNS #
077701613
City
Honolulu
State
HI
Country
United States
Zip Code
96817
White, Lon R; Edland, Steven D; Hemmy, Laura S et al. (2016) Neuropathologic comorbidity and cognitive impairment in the Nun and Honolulu-Asia Aging Studies. Neurology 86:1000-8
Karino, Shigehiko; Willcox, Bradley J; Fong, Kaon et al. (2015) Total and differential white blood cell counts predict eight-year incident coronary heart disease in elderly Japanese-American men: the Honolulu Heart Program. Atherosclerosis 238:153-8
Zeng, Yi; Chen, Huashuai; Ni, Ting et al. (2015) GxE interactions between FOXO genotypes and drinking tea are significantly associated with prevention of cognitive decline in advanced age in China. J Gerontol A Biol Sci Med Sci 70:426-33
Morris, Brian J; Chen, Randi; Donlon, Timothy A et al. (2015) Association Analysis of FOXO3 Longevity Variants With Blood Pressure and Essential Hypertension. Am J Hypertens :
Morris, Brian J; Donlon, Timothy A; He, Qimei et al. (2015) Genetic analysis of TOR complex gene variation with human longevity: a nested case-control study of American men of Japanese ancestry. J Gerontol A Biol Sci Med Sci 70:133-42
Morris, Brian J; Carnes, Bruce A; Chen, Randi et al. (2015) Genetic variation in the raptor gene is associated with overweight but not hypertension in American men of Japanese ancestry. Am J Hypertens 28:508-17
Huh, Ji Young; Ross, George Webster; Chen, Randi et al. (2015) Total and differential white blood cell counts in late life predict 8-year incident stroke: the Honolulu Heart Program. J Am Geriatr Soc 63:439-46
Morris, Brian J; Willcox, Donald Craig; Donlon, Timothy A et al. (2015) FOXO3: A Major Gene for Human Longevity - A Mini-Review. Gerontology 61:515-25
Higuchi, Masaya; Chen, Randi; Abbott, Robert D et al. (2015) Mid-life proteinuria and late-life cognitive function and dementia in elderly men: the Honolulu-Asia Aging Study. Alzheimer Dis Assoc Disord 29:200-5
Willcox, Donald Craig; Scapagnini, Giovanni; Willcox, Bradley J (2014) Healthy aging diets other than the Mediterranean: a focus on the Okinawan diet. Mech Ageing Dev 136-137:148-62

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