Association of reproductive factors, sedentary behavior, and genetic factors with aging in postmenopausal women: the Women’s Health Initiative

Background: In the United States, the aging population is rapidly growing. By 2060, it is expected that 12 million women will be ages 85 years and older. However, determinants of longevity and healthy aging in women are not fully understood. This dissertation had three objectives: 1) Determine whether ages at menarche and menopause and reproductive lifespan were associated with survival to age 90, termed “exceptional longevity;” 2) Determine whether genetic factors associated with longevity in prior studies among populations of European descent were associated with survival to ages 85 and 90 and healthy aging in white, African-American, and Hispanic women; and 3) Determine whether accelerometer-measured and self-reported sedentary time were associated with leukocyte telomere(definition) length (LTL), a purported biomarker of aging, among older women. Methods: Three studies were conducted among participants from the Women’s Health Initiative, a longitudinal study investigating major determinants of chronic diseases in postmenopausal women. Study one was a prospective study among 16,251 women who had potential to survive to age 90 as of August 29, 2014. Study two was a prospective study among 11,154 women who could survive to age 85 as of August 29, 2014 and used genetic data from multiple genome-wide association studies. Study three was a cross-sectional study among 1,481 women with information on either accelerometer-measured or self-reported sedentary time. All studies consisted of racially diverse samples.Results: In study one, the odds of exceptional longevity were elevated among women with later menarche, later menopause, and longer reproductive lifespan. In study two, three variants at APOE were associated with survival to age 90 and healthy aging in white women, and seven variants at a novel locus were associated with survival to age 85 in Hispanic women. In study three, among women at or below the median level of moderate-to-vigorous intensity physical activity (MVPA), higher accelerometer-measured sedentary time was associated with shorter LTL. Among women with higher MVPA levels, sedentary time was not associated with LTL. Conclusions: Findings suggest that reproductive and genetic factors may be associated with late-age survival and that a high level of inactivity may be associated with short LTL.