title: A transcription elongation factor that links signals from the reproductive system to lifespan extension in Caenorhabditis elegans.
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.
authors.affiliation: Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Arjumand
authors.initials: A
authors.lastname: Ghazi
authors.forename: Sivan
authors.initials: S
authors.lastname: Henis-Korenblit
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kenyon
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000254:growth & development / Q000378:metabolism; D008136:Longevity; D008297:Male; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism*; D012098:Reproduction; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D010445:Peptide Elongation Factors; D014157:Transcription Factors; C580768:TCER-1 protein, C elegans