Date on Master's Thesis/Doctoral Dissertation

5-2014

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Epidemiology and Population Health

Committee Chair

Kerber, Richard A.

Committee Co-Chair (if applicable)

O'Brien, Elizabeth

Committee Member

O'Brien, Elizabeth

Committee Member

Taylor, Kira C.

Committee Member

Groves, Frank D.

Committee Member

Mukamal, Kenneth J.

Author's Keywords

Metabolism; Epidemiology

Subject

Oxidative stress; Aging--Health aspects

Abstract

Oxidative stress has been implicated in aging and age-related diseases. Using three distinct studies, this dissertation examines associations between lifestyle factors and oxidative stress, and their effects on advanced glycation end products, telomere length, and type II diabetes. Carboxymethyl-lysine (CML), an advanced glycation end-product, has been linked to oxidative stress, cardiovascular and other age-related diseases. The first study investigates the association between sleep disordered breathing (SDB), a source of oxidative stress, and CML. 1002 participants with sleep data from the Cardiovascular Health Study (CHS) were analyzed. SDB was not significantly associated with CML, but after stratification by gender and hemoglobin it was found that among female subjects with higher hemoglobin levels, those with more severe SDB had a significantly higher CML concentration, while the reverse was observed among males. Telomere length is another biomarker of cumulative exposure to oxidative stress and an indicator of aging. In the second study, 974 participants from the Framingham Heart Study were analyzed to investigate the role of modifiable factors known to affect oxidative stress including obesity, cigarette smoking, excessive alcohol consumption, and physical inactivity, on telomere length. Age, gender, BMI, and alcohol consumption were found to significantly influence telomere length. Diabetes and its complications have roots in oxidative stress. Sleep disturbance, especially sleep apnea, is a potential source of oxidative stress. A total of 9635 participants in the first National Health and Nutrition Examination Survey were followed from 1982 to 1992. Time to diabetes was modeled as a function of sleep quality and quantity with adjustment for potential confounders. Sleep quality, but not sleep quantity, was significantly associated with type II diabetes. In conclusion, oxidative stress plays a vital role in aging and age-related diseases. This dissertation emphasizes the importance of good sleep hygiene, healthy weight, and moderate alcohol consumption to curb the burden of oxidative stress on the human system. These findings may be considered in the policy framework of interventions aimed at reducing age-related diseases, to promote healthier aging and longevity.

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