Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Apr 12;7(15):19185-92.
doi: 10.18632/oncotarget.8313.

Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans

Yan-Hui Li  1 , Gai-Gai Zhang  2
Affiliations

Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans

Yan-Hui Li et al. Oncotarget. .

Abstract

DAF-16, the C. elegans FOXO transcription factor, is an important determinant in aging and longevity. In this work, we manually curated FOXODB http://lyh.pkmu.cn/foxodb/, a database of FOXO direct targets. It now covers 208 genes. Bioinformatics analysis on 109 DAF-16 direct targets in C. elegans found interesting results. (i) DAF-16 and transcription factor PQM-1 co-regulate some targets. (ii) Seventeen targets directly regulate lifespan. (iii) Four targets are involved in lifespan extension induced by dietary restriction. And (iv) DAF-16 direct targets might play global roles in lifespan regulation.

Keywords: C. elegans; FOXO direct targets; Gerotarget; bioinformatics; insulin signaling; lifespan.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST

All the authors declare that they have no competing interests.

Figures

Figure 1
Figure 1. Workflow
We first searched PubMed with FOXOs keywords and found more than 2700 papers. Through manually reading these papers, we got 208 FOXOs direct targets. Inparanoid was used to map FOXOs targets to their orthologs in C. elegans. And 109 genes were found eventually. Bioinformatics analysis on the 109 genes were done including comparison with previous results, transcription factor binding site enrichment, lifespan regulation and network topological feature analysis. And we built a database to make all data easily accessible.
Figure 2
Figure 2. FOXODB database
FOXODB is a database aiming at collecting experimentally verified direct targets of FOXOs. FOXODB is well designed and friendly to user. User could easily browse, search and download the genes.
Figure 3
Figure 3. Network topological features of DAF-16 direct targets
The network topological features of DAF-16 direct targets were shown. ‘All’ represents all proteins in the network. ‘DAF-16 targets’ represents the 109 DAF-16 direct targets in C. elegans. ‘DAF-16 targets & longevity’ represents the DAF-16 direct targets that regulate lifespan. Figure A is the average degree, Figure B is the average K-core, and Figure C is the average of target neighbor ratio.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature. 1993;366:461–464. - PubMed
    1. Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, Li H, Kenyon C. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature. 2003;424:277–283. - PubMed
    1. McElwee J, Bubb K, Thomas JH. Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF-16. Aging Cell. 2003;2:111–121. - PubMed
    1. Dong MQ, Venable JD, Au N, Xu T, Park SK, Cociorva D, Johnson JR, Dillin A, Yates JR., 3rd Quantitative mass spectrometry identifies insulin signaling targets in C. elegans. Science. 2007;317:660–663. - PubMed
    1. Schuster E, McElwee JJ, Tullet JM, Doonan R, Matthijssens F, Reece-Hoyes JS, Hope IA, Vanfleteren JR, Thornton JM, Gems D. DamID in C. elegans reveals longevity-associated targets of DAF-16/FoxO. Mol Syst Biol. 2010;6:399. - PMC - PubMed

MeSH terms

LinkOut - more resources