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PLoS Genet. 2016 Apr 12;12(4):e1005956. doi: 10.1371/journal.pgen.1005956. eCollection 2016 Apr.

Deactivation of the GATA Transcription Factor ELT-2 Is a Major Driver of Normal Aging in C. elegans.

Author information

1
Departments of Genetics and Developmental Biology, Stanford University Medical Center, Stanford, California, United States of America.
2
Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California, San Diego, La Jolla, California, United States of America.
3
Editas Medicine, Cambridge, Massachusetts, United States of America.
4
School of Life Sciences, Tsinghua University, Beijing, China.

Abstract

To understand the molecular processes underlying aging, we screened modENCODE ChIP-seq data to identify transcription factors that bind to age-regulated genes in C. elegans. The most significant hit was the GATA transcription factor encoded by elt-2, which is responsible for inducing expression of intestinal genes during embryogenesis. Expression of ELT-2 decreases during aging, beginning in middle age. We identified genes regulated by ELT-2 in the intestine during embryogenesis, and then showed that these developmental genes markedly decrease in expression as worms grow old. Overexpression of elt-2 extends lifespan and slows the rate of gene expression changes that occur during normal aging. Thus, our results identify the developmental regulator ELT-2 as a major driver of normal aging in C. elegans.

PMID:
27070429
PMCID:
PMC4829211
DOI:
10.1371/journal.pgen.1005956
[Indexed for MEDLINE]
Free PMC Article

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