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CIRCADIAN MECHANISMS OF CALORIE RESTRICTION IN DELAYING AGING

Makwana, Kuldeep, Makwana
http://rave.ohiolink.edu/etdc/view?acc_num=csu1543844626233009

Abstract Details

2018, Doctor of Philosophy in Regulatory Biology, Cleveland State University, College of Sciences and Health Professions.
Calorie Restriction (CR) is a dietary intervention known to delay age associated pathologies and conditions. Its beneficial effects on the longevity are reported in variety of organisms ranging from unicellular to multi-cellular organisms like mammals. Various mechanisms have been proposed for the beneficial effect of CR on the lifespan. One of the proposed mechanisms by which CR brings about its beneficial effects on the lifespan is regulation of protein synthesis. Various studies have demonstrated an increase in protein synthesis under CR, some claimed inhibition of protein synthesis under CR, and some claimed no effect on protein synthesis under CR. In this work, using comprehensive circadian experimental setup, I have demonstrated inhibition of global protein synthesis under CR diet in mouse liver. Animals were subjected to two months of CR followed by polysome profiling of liver tissue. Protein translation was down-regulated in the liver of CR animals at all time points but after four hours of feeding, where it was found to be higher than AL animals. Transcripts associated with polysomes were isolated and mRNA-sequencing was performed. CR was found to be involved in the temporal reprogramming of circadian rhythms in protein translation. Furthermore, the effect of CR on differential translation was studied. mRNA-Sequencing assayed 26,913 transcripts associated with polysomes, 0.1% of the total number of transcripts were found to be differentially abundant in the polysomes. My study has revealed, for the first, CR mediated induced expression of ACOT enzymes which are known to be involved fat metabolism. Thus, I demonstrated circadian mechanism of calorie restriction in regulating metabolism via controlling the gene expression at the level of translation in CR animals.
Roman Kondratov, Ph.D. (Advisor)
Girish Shukla, Ph.D. (Committee Chair)
Justin Lathia, Ph.D. (Committee Member)
Aaron Severson, Ph.D. (Committee Member)
Yana Sandlers, Ph.D. (Committee Member)
Crystal Weyman, Ph.D. (Committee Member)
152 p.
Biology
Calorie Restriction; Fat Metabolism; RNA Sequencing; Aging

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Citations

  • Makwana, Makwana, K. (2018). CIRCADIAN MECHANISMS OF CALORIE RESTRICTION IN DELAYING AGING [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1543844626233009

    APA Style (7th edition)

  • Makwana, Makwana, Kuldeep. CIRCADIAN MECHANISMS OF CALORIE RESTRICTION IN DELAYING AGING. 2018. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1543844626233009.

    MLA Style (8th edition)

  • Makwana, Makwana, Kuldeep. "CIRCADIAN MECHANISMS OF CALORIE RESTRICTION IN DELAYING AGING." Doctoral dissertation, Cleveland State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=csu1543844626233009

    Chicago Manual of Style (17th edition)

csu1543844626233009
211
© 2018, some rights reserved.Creative Commons License CIRCADIAN MECHANISMS OF CALORIE RESTRICTION IN DELAYING AGING by Kuldeep Makwana Makwana is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Cleveland State University and OhioLINK.