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Circadian deep sequencing reveals stress-response genes that adopt robust rhythmic expression during aging

Kuintzle, Rachael C. and Chow, Eileen S. and Westby, Tara N. and Gvakharia, Barbara O. and Giebultowicz, Jadwiga M. and Hendrix, David A. (2017) Circadian deep sequencing reveals stress-response genes that adopt robust rhythmic expression during aging. Nature Communications, 8 . Art. No. 14529. ISSN 2041-1723. PMCID PMC5321795. https://resolver.caltech.edu/CaltechAUTHORS:20170317-105351401

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Abstract

Disruption of the circadian clock, which directs rhythmic expression of numerous output genes, accelerates aging. To enquire how the circadian system protects aging organisms, here we compare circadian transcriptomes in heads of young and old Drosophila melanogaster. The core clock and most output genes remained robustly rhythmic in old flies, while others lost rhythmicity with age, resulting in constitutive over- or under-expression. Unexpectedly, we identify a subset of genes that adopted increased or de novo rhythmicity during aging, enriched for stress-response functions. These genes, termed late-life cyclers, were also rhythmically induced in young flies by constant exposure to exogenous oxidative stress, and this upregulation is CLOCK-dependent. We also identify age-onset rhythmicity in several putative primary piRNA transcripts overlapping antisense transposons. Our results suggest that, as organisms age, the circadian system shifts greater regulatory priority to the mitigation of accumulating cellular stress.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://dx.doi.org/10.1038/ncomms14529DOIArticle
http://www.nature.com/articles/ncomms14529PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321795/PubMed CentralArticle
Additional Information:© The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ Received: 01 November 2016. Accepted: 09 January 2017. Published online: 21 February 2017. We thank Mark Dasenko for performing sequencing, Dr P. Andrew Karplus for helpful discussions, Dr Jeff Price for anti-PER antibody and Bloomington Drosophila Stock Center for flies. This work was supported by the National Institute of Aging of NIH under award number R01AG045830 to J.M.G. and R21AG052950 to J.M.G. and D.A.H. Author Contributions: J.M.G., R.C.K., E.S.C. and D.A.H. designed the experiments. R.C.K., E.S.C., T.N.W., J.M.G. and B.O.G. conducted the experiments. R.C.K. and D.A.H. performed the bioinformatics analysis. R.C.K., E.S.C., T.N.W., B.O.G. and D.A.H. prepared the figures. R.C.K. drafted the manuscript; J.M.G., R.C.K., E.S.C. and D.A.H. provided critical edits. The authors declare no competing financial interests. Data availability: Data for RNA-seq and processed files have been deposited to NCBI Gene Expression Omnibus (GEO) under the accession number GSE81100. RNA-seq expression plots for all FlyBase genes and isoforms are available at: http://hendrixlab.cgrb.oregonstate.edu/youngAndOldExpression.html. All other data supporting the findings of this study are included in the manuscript and its supplementary files or are available from the corresponding authors on request.
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Funding AgencyGrant Number
NIHR01AG045830
NIHR21AG052950
PubMed Central ID:PMC5321795
Record Number:CaltechAUTHORS:20170317-105351401
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170317-105351401
Official Citation:Kuintzle, R. C. et al. Circadian deep sequencing reveals stress-response genes that adopt robust rhythmic expression during aging. Nat. Commun. 8, 14529 doi: 10.1038/ncomms14529 (2017).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75200
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:17 Mar 2017 18:18
Last Modified:03 Oct 2019 16:47

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