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Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Public Health

Year Degree Awarded

2018

Month Degree Awarded

September

First Advisor

Elena T. Carbone

Second Advisor

Richard J. Wood

Third Advisor

Katherine W. Reeves

Subject Categories

Nutrition | Nutritional Epidemiology

Abstract

Background: Telomeres are the noncoding nucleotide sequences at the end of eukaryotic chromosomes, serving to protect DNA during mitotic division. Given their guanine-rich structure, telomeres are highly susceptible to oxidative damage often mediated by inflammation. Recently, telomere attrition and dysfunction have been associated with age-related diseases, including cardiovascular disease, type 2 diabetes, Alzheimer’s disease, and certain cancers. Several modifiable risk factors have also been associated with shortened telomere length, including physical inactivity, obesity, stress, smoking, and poor diet.

Objective: We examined the relations between vitamin B12 status, folate status, and iron status, relative to telomere length in eligible participants in the 1999-2002 US National Health and Nutrition Examination Survey.

Design: Eligible participants had no evidence of kidney or liver disease, or pregnancy, and had complete data on outcome, exposure and covariates (n = 5,941). Low B12 status was defined as serum B12 ≤148 pmol/L or serum methylmalonic acid concentration ≥210 nmol/L. Folate status was defined as serum folate ≤13.4 nmol/L (suboptimal), and ≥45.3 nmol/L (elevated). Iron (Fe) status was defined as meeting ≥2 of the following criteria: serum ferritin ≤15 µg/L, erythrocyte protoporphyrin >80 µg/dL, transferrin saturation (TS)50%, serum Fe ≥155 µg/L (women) or ≥160 µg/L (men), or serum ferritin ≥150 µg/L (women) or ≥200 µg/L (men) with no signs of inflammation.

Results: After controlling for covariates including, age, race/ethnicity, sex, BMI, education level, smoking, alcohol intake, and blood glucose level, low B12 status in the presence of elevated folate status was significantly associated with a shorter mean telomere length in middle-aged adults. Elevated iron status was associated with a shorter mean telomere length in adult men and women.

Conclusion: In middle-aged adults, low vitamin B12 in the presence of elevated folate status was associated with significant telomeric attrition equivalent to 27 years of additional biological aging. The shorter mean telomere length associated with an elevated iron status was equivalent to 2.6 years of additional biological aging in adult men and women. Thus, poor micronutrient status is associated with shorter mean telomere lengths in adult men and women.

Available for download on Sunday, September 01, 2019

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