Author ORCID Identifier
Year of Publication
Doctor of Philosophy (PhD)
Pharmacology and Nutritional Sciences
Dr. Eric Blalock
Complaints associated with aging, including cognitive deficits and sleep loss, are highly prevalent and negatively impact quality of life. Further, with increased age, humans are also more likely to experience new-onset psychosocial stressors, such as divorce, loss of a spouse, and social isolation. Stress has detrimental consequences that in many ways parallel the effects of aging on sleep and cognition. The long-standing stress/ glucocorticoid hypotheses of brain aging posit that stress exposure exacerbates aging symptoms, and extensive prior studies have shown that early life stress exposure does worsen phenotypic aging symptoms. However, despite its prevalence in aged humans, little basic research has investigated the response of aged subjects to new-onset psychosocial stress. Prior work in our lab showed aged rodents to be hyporesponsive to a new-onset acute psychosocial stress. Here, we assess the age-course of this acute response, as well as evaluate the consequences of chronic psychosocial stress exposure in aged animals. Our lab tested two hypotheses. First, we hypothesized that mid-aged animals will have an intermediate response between young and aged to acute psychosocial stress. Second, we hypothesized that aged animals’ will continue to be hyporesponsive during a chronic psychosocial stress.
We focused on mid-aged animals for our first study because this age-point serves as the transition period from young to aged and could hold some key information about the transition from healthy to unhealthy brain aging. We used restraints to induce stress, the Morris water maze to test cognitive function, and telemetry devices to characterize sleep architecture and body temperature. We showed that, among age-related acute stress hyposensitive findings (deep sleep loss, hyperthermia, and cognitive deficit), mid-aged animals were hyporesponsive to sleep, but not body temperature or maze performance. This suggests that the failure to manifest a sleep response to stress precedes cognitive and body temperature related stress insensitivity.
In our second study, we investigated the influence of new-onset chronic psychosocial stress (three hours per day, four days per week for one month) in young and aged rodents. Aged animals were hyporesponsive to multiple common indicators of stress including distress during the restraint, weight loss, and cognitive deficits, all of which were easily detectable in young animals. These results suggest that the age-related blunting of the stress response is sustained from acute to chronic exposures. While the hyporesponsiveness may seem advantageous in the aged, a failed response could also be maladaptive, reducing a subject’s ability to compensate for a changing environment. Together, this work supports prior observations that stress exposure makes young animals more aged like. Aged animals also showed a more limited response to stress, suggesting that age itself may act as an occluding stressor. Finally, this work points to deep sleep promoting interventions as potential therapeutic strategies for managing age-related changes in stress response.
Digital Object Identifier (DOI)
Hargis, Kendra E., "Deep Sleep, Cognition, Body Weight, Body Temperature, and Behavioral Distress Responses to New Onset Psychosocial Stressors are Blunted with Age in Male F344 Rats" (2016). Theses and Dissertations--Pharmacology and Nutritional Sciences. 16.