Award Date

5-1-2019

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Environmental and Occupational Health

First Committee Member

Francisco S. Sy

Second Committee Member

Rachelle Rodriguez

Third Committee Member

Mark P. Buttner

Fourth Committee Member

Jennifer Pharr

Fifth Committee Member

Du Feng

Number of Pages

138

Abstract

Introduction: Telomeres are nucleoprotein structures located at the ends of eukaryotic chromosomes, thought to protect the DNA from damage. As a person experiences stressors, harmful exposures, and other diseases throughout their life, telomeres are thought to become damaged and their length shortened, decreasing their ability to protect the DNA. Nutrition is an important aspect of healthy aging. Preservation of telomere length (TL) is thought to be one of the mechanisms by which good nutrition can delay or prevent the development of chronic disease and death. Recent evidence of preservation of TL with good nutrition is promising. Thus, the aim of this dissertation is to study the relationship of TL with nutrition and mortality, which will be accomplished through three distinct, but ancillary aims. The first aim of this research is to examine rates of age-related TL change and evaluate variability in the rate by gender, chronic stress, and chronic diseases. The second aim is to comprehensively examine the linear associations between different macro- and micro-nutrients and healthy eating and TL. The third aim is to assess the associations of TL with survival and lifespan.

Methods: For the first and second study aim, cross-sectional data on individuals, aged ≥ 20 years with a TL measurement available, were included from the National Health and Nutrition Examination Survey, years 1999-2002. Crude and adjusted linear regression models were used to estimate the rate of decline in TL across 10-year age categories, and any variations in the decline with respect to sex, measure of chronic stress, and presence of chronic diseases. To evaluate the associations between TL and a variety of macro- and micro-nutrients, and healthy eating, multivariate linear regression models using energy-adjusted nutrients were implemented. For the third aim of the study, data on 328 elderly (oldest-old) men from the Zutphen (The Netherlands) and Cretan (Greece) Elderly Study, with available TL measurement in 2000 were included.Follow-up for vital status was available until September 2015. Kaplan-Meier survival estimation assessed differences in survival between men with short and long TL. Univariate and multivariable Cox proportional hazard models assessed the associations of TL (standardized continuous measure) on survival. Linear regression models assessed the relation of TL on age at death.

Results: In an adjusted model, the population rate of decline in TL with age was consistent and linear for only three age categories: 20-29 (β=-0.0196, 95% CI: -0.0360, -0.0032), 50-59 (β=-0.0200, 95% CI: -0.0326, -0.0074) and 70-79 (β=-0.0164, 95% CI: -0.0318, -0.0010) years. The population rate of decline in TL with age was significantly greater for males and those with high allostatic load (a measure of chronic stress) and a history of comorbidities. When the population rate of decline in TL was analyzed by gender in 10-year age bins, a fairly consistent yet statistically non-significant decline for males was observed; however, a trough in the rate was observed for females in the age categories 20-29 years (β=-0.0283, 95% CI: -0.0468, -0.0099) and 50-59 years (β=-0.0216, 95% CI: -0.0396, -0.0036). To further elucidate the gender difference observed in the primary analyses, secondary analyses were conducted with reproductive and hormonal status; a significant inverse association was found between TL and parity, menopause, and age at menopause. In a linear regression model to study associations between TL and nutrients, adjusted for demographics and health-related behaviors, of the macronutrients examined, total fat (β= -83.24, 95% CI: -153.31, -13.17), mono-unsaturated (β= -107.40, 95% CI: -175.39, -39.40) and poly-unsaturated fatty acids (β=-54.01, 95% CI: -99.81, -8.19) were inversely associated with TL. Of the micro-nutrients examined, potassium was the only element (β= 90.17, 95% CI: 7.54, 172.79) and riboflavin or Vitamin B2 (β= 85.04, 95% CI: 1.53, 168.54) was the only vitamin that was significantly associated with TL in fully adjusted models. However, Vitamin A, B12, and E were inversely associated with TL in energy adjusted models. After adjustment for total calorie, demographic, and health-related behaviors, the overall healthy eating index (HEI) score was positively associated with TL (β= 3.42, 95% CI: 0.29, 6.53, p-value=0.033); every unit increase in HEI score increased the TL by 3.42 base pairs. In the mortality study, all but nine men were deceased by the end of the study period. TL was not related to socio-demographic factors, lifestyle factors and prevalent chronic diseases. Kaplan-Meier survival analysis did not show statistically significant differences in all-cause or cardiovascular mortality between long and short TL groups. In Cox proportional hazards models, long TL was not associated with all-cause (HR: 0.90, 95%CI: 0.68 - 1.17) and cardiovascular mortality (HR: 0.96, 95%CI 0.62 - 1.50). In linear regression models, TL was not a significant predictor of age at death. Findings were also not significant when analyzed separately for the Zutphen and Cretan cohort.

Conclusions: TL was shorter with increasing age and this decline was modified by gender, chronic stress and comorbidities; individuals with chronic morbidity and/or chronic stress and females in their twenties and fifties experienced greater decline. Female reproductive factors, i.e., parity and menopause, were associated with TL. Certain nutrients, as well as healthy eating in general, are associated with preservation of TL. Health gains associated with telomere preservation could potentially be achieved relatively easily through promotion of healthy and adequate diets. Finally, the lack of associations of TL with mortality and lifespan in the elderly men from Zutphen and Crete is consistent with previous literature.

Keywords

Allostatic load; Comorbidities; Mortality; NHANES; Nutrients; Telomere length

Disciplines

Biostatistics | Epidemiology | Public Health

Language

English


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