UCSF

The reproductive tissues of C. elegans influence how the whole animal ages. The two cell types of the reproductive system have opposite effects on longevity. The germ cells inhibit a long lifespan, and the somatic reproductive tissues (somatic gonad) promote a long lifespan in the absence of the germ cells. How the somatic gonad promotes the longevity of other tissues is not well understood.

Here, we find that the somatic gonad has two effects on other tissues. First, the somatic gonad activates DAF-12, a nuclear hormone receptor that extends lifespan, through its ligand, dafachronic acid. Next, the somatic gonad ensures the full transcriptional activity of the FOXO transcription factor, DAF-16. Interestingly, the somatic gonad does not affect the entry of DAF-16/FOXO into the nucleus where it acts to promote longevity. The germ cells, however, do affect where DAF-16/FOXO is located within a cell. This supports the idea that the somatic gonad and germ cells affect lifespan, at least in part, through distinct mechanisms.

To extend lifespan, the somatic gonad activates both DAF-12/NHR and DAF-16/FOXO. However, we find that the two transcription factors do not operate in a simple linear pathway, with one being fully required for the activity of the other. Instead, we find the two transcription factors regulate distinct sets of genes. Additionally, the two transcription factors have modest effects on the activity of the other. That is, DAF-12/NHR is partially required for the full activity of DAF-16/FOXO, and vice versa.

To summarize, the somatic gonad affects lifespan by modulation of the activities of two transcription factors, DAF-16/FOXO and DAF-12/NHR, which work in parallel to promote longevity.