Abstract
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.
Highlights
When the germline of C. elegans is removed, either by laser ablation or by mutations that block germline-stem cell proliferation, the animals live approximately 60% longer than normal [1,2]
We have identified a gene called tcer-1 that promotes the longevity of the roundworm Caenorhabditis elegans when its germ cells are removed
Our experiments imply that when the germ cells of worms are removed, TCER-1 collaborates with a transcription factor called DAF-16/FOXO to express genes that contribute to increased longevity
Summary
When the germline of C. elegans is removed, either by laser ablation or by mutations that block germline-stem cell proliferation, the animals live approximately 60% longer than normal [1,2]. This longevity is not a simple consequence of sterility, as removing the entire gonad (the germ cells as well as the somatic reproductive tissues) does not extend lifespan [1]. At least two transcription factors, the FOXOfamily transcription factor DAF-16/FOXO [7,8,9] and the nuclear hormone receptor DAF-12 [10], are required for germ-cell loss to extend lifespan in C. elegans [1].
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