Advisory Committee Chair
Advisory Committee Members
Matthew S Alexander
Date of Award
Degree Name by School
Master of Science (MS) College of Arts and Sciences
Exercise is a powerful behavioral intervention against Central Nervous System (CNS) aging1–3 and plays an essential role in maintaining healthy neurocognitive function and immune metabolism in the aging brain3. We have developed a new transgenic mouse model that moderately over-expresses transcription factor master regulator of proteostasis, Transcription Factor E-B (TFEB), in skeletal muscle (cTFEB;HSACre mice). Despite living sedentary lifestyles, our model of enhanced skeletal muscle proteostasis shows significantly ameliorated proteotoxicity, increased BDNF levels and neurogenesis while improving neurocognitive function and decreasing neuroinflammation in the aging CNS4,5. These neuroprotective effects are markedly reminiscent of those observed in the aging CNS post-exercise6,7, suggesting enhancing muscle proteostasis may be sufficient to replicate the local and systemic benefits of exercise. Indeed, skeletal muscle is a powerful endocrine organ, secreting bioactive molecules, cytokines, known as ‘myokines’, such as irisin/FNDC5 an cathepsin B that can modify CNS metabolism and function, which very likely contribute to the exercise-associated benefits on cognition6,8. Exercise activates the production and secretion of these myokines from skeletal muscle into circulation, directly implicating skeletal muscle metabolism in the CNS’s response to exercise9–11. iv However, to date, the precise origin and function of these exercise-responsive, proneurogenic circulating factors remain largely unexplored. Therefore, I hypothesize that changes in skeletal muscle-originating circulatory factors will be similar between our sedentary cTFEB;HSACre mice and wild-type voluntary running (exercised) mice.
Patterson, Dalton Chase, "Characterization of Exercise-Associated Skeletal Muscle Secreted Factors Through Aging" (2022). All ETDs from UAB. 564.