Type
Text
Type
Dissertation
Advisor
Canli, Turhan | Kritzer, Mary | Furie, Martha | Thomsen, Gerald | Robinson, John.
Date
2014-12-01
Keywords
Genetics
Department
Department of Genetics.
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/77627
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
Telomeres are repetitive nucleoprotein complexes at the ends of chromosomes that provide a protective cap for genomic DNA. Telomere shortening leads to cellular senescence or apoptosis. Accordingly, telomere length is considered both a mechanism and marker for aging. Increased exposure to chronic stress is associated with shorter telomere length. In addition, differences in stress reactivity have been associated with telomere length. Here I will describe several studies identifying neural circuits associated with such telomere shortening, an evaluation of saliva as an appropriate biomaterial to measure telomere length, and an exploration of the role of microRNAs as mediators of stress-related telomere shortening. Abnormalities in the function of stress related neural circuitry might be one mechanism of stress-related telomere shortening. We examined the relationship between activation in stress-related neural circuitry at rest, or during an acute psychosocial stress task, and telomere length in a healthy population. We observed that subjects with shorter telomere length showed increased activation in the anterior cingulate cortex (ACC) and the amygdala at rest. We also found that telomere length negatively correlated with activity in the ACC, hippocampus and medial prefrontal cortex during an acute stress task. These findings suggest that increased neural reactivity may be one mechanism for individual differences in telomere length. The majority of studies of telomere shortening use leukocyte telomere length as a biomarker, which requires a blood draw. While telomere length varies across tissues, the rate of telomere shortening appears to be similar across tissue types. We have determined that relative telomere length in saliva is correlated with telomere length in leukocytes, indicating that saliva is an appropriate proxy for blood to measure telomere length. To date, limited research has been done to identify the mechanism by which stress affects telomere length. Psychological stress has been associated with increased levels of specific miRNAs, and our laboratory has compiled a list of miRNAs that undergo expression changes in response to an acute stressor. These miRNAs are predicted to target several proteins that elongate and protect telomeres. However, our investigations do not support a role for miRNAs in stress-related telomere shortening. | 125 pages
Recommended Citation
Izzi, Stephanie, "Neural Correlates and Peripheral miRNAs Associated with Stress-Related Telomere Shortening" (2014). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 3422.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/3422