Cell Non-Autonomous Modulation of Longevity by TORC1 and AMPK
Citation
Zhang, Yue. 2018. Cell Non-Autonomous Modulation of Longevity by TORC1 and AMPK. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.Abstract
Human life expectancy has increased dramatically over the last century. With more people living into older age, age-related chronic diseases have become a prominent challenge for biomedical research. AMP-activated protein kinase (AMPK) and target of rapamycin complex 1 (TORC1) are two important pathways that can be modulated to increase longevity and ameliorate multiple age-related diseases. However, the interaction between AMPK and TORC1 in longevity remains unknown. My main project used Caenorhabditis elegans, a genetically tractable model organism, to elucidate genetic interaction and site of requirement in the modulation of longevity for AMPK and TORC1. I found that AMPK activity, specifically in neurons, is essential for longevity under conditions of reduced TORC1 signaling (Chapter 2). I further elucidated a novel mechanism in which TORC1 in neurons modulates aging of the whole organism. I found that neuronal TORC1 communicates with peripheral tissues via neuropeptide signaling and drives aging in peripheral tissues by causing mitochondrial fragmentation (Chapter 3). I also included other work I have done on understanding mechanisms downstream of AMPK longevity (Chapter 4) and elucidating the critical role of hydrogen sulfide production in longevity via dietary restriction (Chapter 5). Taken together, all the results suggest that molecular pathways that respond to nutrients are critical modulators of lifespan, providing new targets that can be utilized to develop interventions that will potentially promote health aging.Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:41127169
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