Calorie Restriction Effect on Circadian Clock Gene Expression
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ndltd-OhioLink-oai-etd.ohiolink.edu-csu14722949112021-08-03T06:38:29Z Calorie Restriction Effect on Circadian Clock Gene Expression Patel, Sonal Arvind Biology Molecular Biology Circadian clock gene expression Igf Insulin Bmal1 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. 2016-08-29 English text Cleveland State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=csu1472294911 http://rave.ohiolink.edu/etdc/view?acc_num=csu1472294911 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
language |
English |
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NDLTD |
topic |
Biology Molecular Biology Circadian clock gene expression Igf Insulin Bmal1 |
spellingShingle |
Biology Molecular Biology Circadian clock gene expression Igf Insulin Bmal1 Patel, Sonal Arvind Calorie Restriction Effect on Circadian Clock Gene Expression |
author |
Patel, Sonal Arvind |
author_facet |
Patel, Sonal Arvind |
author_sort |
Patel, Sonal Arvind |
title |
Calorie Restriction Effect on Circadian Clock Gene Expression |
title_short |
Calorie Restriction Effect on Circadian Clock Gene Expression |
title_full |
Calorie Restriction Effect on Circadian Clock Gene Expression |
title_fullStr |
Calorie Restriction Effect on Circadian Clock Gene Expression |
title_full_unstemmed |
Calorie Restriction Effect on Circadian Clock Gene Expression |
title_sort |
calorie restriction effect on circadian clock gene expression |
publisher |
Cleveland State University / OhioLINK |
publishDate |
2016 |
url |
http://rave.ohiolink.edu/etdc/view?acc_num=csu1472294911 |
work_keys_str_mv |
AT patelsonalarvind calorierestrictioneffectoncircadianclockgeneexpression |
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1719440596467187712 |