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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.

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


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.

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