In Caenorhabditis elegans and Drosophila melanogaster, the aging of the soma is influenced by the germline. When germline-stem cells are removed, aging slows and lifespan is increased. The mechanism by which somatic tissues respond to loss of the germline is not well-understood. Surprisingly, we have found that a predicted transcription elongation factor, TCER-1, plays a key role in this process. TCER-1 is required for loss of the germ cells to increase C. elegans' lifespan, and it acts as a regulatory switch in the pathway. When the germ cells are removed, the levels of TCER-1 rise in somatic tissues. This increase is sufficient to trigger key downstream events, as overexpression of tcer-1 extends the lifespan of normal animals that have an intact reproductive system. Our findings suggest that TCER-1 extends lifespan by promoting the expression of a set of genes regulated by the conserved, life-extending transcription factor DAF-16/FOXO. Interestingly, TCER-1 is not required for DAF-16/FOXO to extend lifespan in animals with reduced insulin/IGF-1 signaling. Thus, TCER-1 specifically links the activity of a broadly deployed transcription factor, DAF-16/FOXO, to longevity signals from reproductive tissues.
Bibliographical noteFunding Information:
We are grateful to Shohei Mitani (National Bioresource Project, Tokyo, Japan), David Baillie (C. elegans Gene Expression Consortium funded by Genome British Columbia and Genome Canada) and the Caenorhabditis Genetics Center (supported by the National Institutes of Health- National Center for Research Resources) for providing many of the strains used in this study. Our thanks to S. J. Lee, M. Gaglia, M. Suchanek, A. Kao, D. David, and J. Berman for providing valuable comments on this manuscript, and to members of the Kenyon Lab for advice and support. We are thankful to P. Zhang and M. Cary for reagents and analyses.