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Accession IconSRP170618

DAF-16 stabilizes the aging transcriptome and is activated in mid-aged C. elegans to cope with internal stress

Organism Icon Caenorhabditis elegans
Sample Icon No Downloadable Samples
Technology Badge IconHiSeq X Ten

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Description
The roles and regulatory mechanisms of transcriptome changes during aging are unclear. It has been proposed that the transcriptome suffers decay during aging owing to age-associated down-regulation of transcription factors. In this study, we characterized the role of a transcription factor DAF-16, which is a highly conserved lifespan regulator, in the normal aging process of Caenorhabditis elegans. We found that DAF-16 translocates into the nucleus in aged wild-type worms and activates the expression of hundreds of genes in response to age-associated cellular stress. Most of the age-dependent DAF-16 targets are different from the canonical DAF-16 targets downstream of insulin signaling. This and other evidence suggest that activation of DAF-16 during aging is distinct from activation of DAF-16 due to reduced signaling from DAF-2. Further analysis showed that it is due in part to a loss of proteostasis during aging, at least in part. We also found that without daf-16, dramatic gene expression changes occur as early as on adult day 2, indicating that DAF-16 acts to stabilize the transcriptome during normal aging. Our results thus reveal that normal aging is not simply a process in which the gene expression program descends into chaos due to loss of regulatory activities; rather, there is active transcriptional regulation during aging. Overall design: Transcriptome analyses of fer-15(b26ts) and daf-16(mu86);fer-15(b26ts) worms were carried out in three biological replicates. Worms were grown on High Growth (HG) plates supplemented with OP50 bacteria at 25 °C and harvested on adult day 1 through day 7.
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