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Sonal Patel Dissertation 2016.pdf (4.44 MB)

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Calorie Restriction Effect on Circadian Clock Gene Expression

Patel, Sonal Arvind
http://rave.ohiolink.edu/etdc/view?acc_num=csu1472294911

Abstract Details

2016, Doctor of Philosophy in Regulatory Biology, Cleveland State University, College of Sciences and Health Professions.
Calorie Restriction (CR) is a powerful paradigm known to delay aging and thus increase longevity in several organisms, from yeast to non-human primates. Many molecular pathways have been proposed to mediate the beneficial effects of CR, however, the mechanism is still unknown. Circadian clock which is an internal time keeping system is regulated by feeding. Thus our aim was to study the effect of CR on the circadian clock. Here we show that CR significantly affects the expression of circadian clock genes in mice at the mRNA and protein levels, suggesting that CR reprograms the clocks at the transcriptional and post-transcriptional level. CR also affected the circadian output through up- or down-regulation of the expression of several clock-controlled transcriptional factors and the longevity candidate genes. CR-dependent effects on some clock gene expression were impaired in the liver of mice deficient for BMAL1, suggesting importance of this transcriptional factor for the transcriptional reprogramming of the clock, however, BMAL1-independent mechanisms exist too. We have shown that Bmal1 deficient mice develop premature aging phenotype and have a shortened lifespan. We decided to apply 30%CR to these mice and found that CR did not increase the lifespan of these Bmal1 mutants, further suggesting that BMAL1 is necessary for full benefits of CR. We also analyzed the plasma levels of IGF-1 and insulin, which were found to be impaired in Bmal1 deficient mice on 30%CR. We propose that CR recruits biological clocks as a natural mechanism of metabolic optimization and synchronization of the several downstream pathways under limited nutrient conditions.
Roman Kondratov, PhD (Advisor)
Barsanjit Mazumder, PhD (Committee Member)
Aaron Severson, PhD (Committee Member)
William Baldwin, M.D., PhD (Committee Member)
173 p.
Biology; Molecular Biology
Circadian clock; gene expression; Igf; Insulin; Bmal1

Recommended Citations

Citations

  • Patel, S. A. (2016). Calorie Restriction Effect on Circadian Clock Gene Expression [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1472294911

    APA Style (7th edition)

  • Patel, Sonal. Calorie Restriction Effect on Circadian Clock Gene Expression . 2016. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1472294911.

    MLA Style (8th edition)

  • Patel, Sonal. "Calorie Restriction Effect on Circadian Clock Gene Expression ." Doctoral dissertation, Cleveland State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=csu1472294911

    Chicago Manual of Style (17th edition)

csu1472294911
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© 2016, all rights reserved.
This open access ETD is published by Cleveland State University and OhioLINK.