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CIRCADIAN REGULATION OF mTOR SIGNALING VIA BMAL1 DEPENDENT MECHANISM

KHAPRE, ROHINI VISHAL
http://rave.ohiolink.edu/etdc/view?acc_num=csu1399025275

Abstract Details

2014, Doctor of Philosophy in Regulatory Biology, Cleveland State University, College of Sciences and Health Professions.
Understanding mechanisms of aging is important for the treatment and prevention of age-associated pathologies. However, these mechanisms are not well understood. Recently we have demonstrated that the circadian clock (an internal time keeping system) regulates longevity in mammals, but the molecular mechanisms are not known. The aim of our current study is to investigate a possible interconnection between the circadian clock and mTORC1 (mammalian target of Rapamycin) signaling pathway. mTORC1 pathway is a nutrient response pathway involved in many cellular processes; many recent studies indicate a role of mTORC1 pathway in aging. Here we demonstrate that circadian system regulates mTORC1 signaling in vivo. Analysis of liver, heart and spleen from WT mice reveals circadian rhythms in phosphorylation of known mTOR targets such as S6K1 and 4EBPs. These rhythms are disrupted in the tissues of BMAL1 KO mice providing potential mechanistic explanation of reduced longevity of these mice. Further analysis of expression of mTORC1 complex components and upstream regulators demonstrated that some of them have circadian rhythms at protein and mRNA levels. Taken together, these results suggest that circadian clock controls aging by regulating mTOR signaling pathway through BMAL1 dependent control of gene expression.
ROMAN KONDRATOV (Advisor)
CRYSTAL WEYMAN (Committee Member)
ALEXANDRU ALMASAN (Committee Member)
VALENTINE BOERNER (Committee Member)
163 p.
Biology; Cellular Biology; Molecular Biology
Circadian Clock; Biological Clock; BMAL1; Aging; Mice; mTOR; signaling pathway; Feeding; Senescence; oxidative stress

Recommended Citations

Citations

  • KHAPRE, R. V. (2014). CIRCADIAN REGULATION OF mTOR SIGNALING VIA BMAL1 DEPENDENT MECHANISM [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1399025275

    APA Style (7th edition)

  • KHAPRE, ROHINI. CIRCADIAN REGULATION OF mTOR SIGNALING VIA BMAL1 DEPENDENT MECHANISM. 2014. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1399025275.

    MLA Style (8th edition)

  • KHAPRE, ROHINI. "CIRCADIAN REGULATION OF mTOR SIGNALING VIA BMAL1 DEPENDENT MECHANISM." Doctoral dissertation, Cleveland State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=csu1399025275

    Chicago Manual of Style (17th edition)

csu1399025275
879
© 2014, all rights reserved.
This open access ETD is published by Cleveland State University and OhioLINK.