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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 .

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