Investigating the Role of Chronic Stress in the Regulation of Telomere Length in Mice

Abstract

Chronic stress is a well-established risk factor for many adverse health effects; however, the mechanism is poorly characterized, and it remains unclear as to how stress influences the onset of age-related disease. Some research has suggested that allostatic load mediates this mechanism through increases in cortisol levels, and this relationship between chronic stress, cortisol elevation, and reduced telomere length has been investigated in humans, rodents, and birds. This thesis utilizes two models of chronic stress – chronic restraint stress (CRS) and repeated corticosterone injection (CORT) – in order to explore the biochemical mechanisms through which stress affects telomere shortening in mice. This research aims to provide evidence for the pivotal role of corticosterone in the regulation of telomere biology as well as in the manifestation of chronic stress as negative physical and behavioral health outcomes. In order to find differences in physical, behavioral, and telomeric changes, mice were examined for corticosterone levels, epinephrine levels, body weight, blood glucose levels, anxiety behaviors, and changes in telomere length of hippocampus, testes, and ten other tissues. Both CRS and CORT mice showed high levels of corticosterone in serum. Differences in telomere homeostasis appeared to be tissue-specific: specifically, CRS and CORT mice showed telomere shortening in brain tissues and telomere lengthening in testes. Further examination of telomerase activity in these tissues will help determine whether telomere length regulation during chronic stress occurs through a telomerase-dependent mechanism.