Insulin-like peptides and the mTOR-TFEB pathway protect hermaphrodites from mating-induced death. Author Cheng Shi, Lauren Booth, Coleen Murphy Publication Year 2019 Type Journal Article Abstract Lifespan is shortened by mating, but these deleterious effects must be delayed long enough for successful reproduction. Susceptibility to brief mating-induced death is caused by the loss of protection upon self-sperm depletion. Self-sperm maintains the expression of a DAF-2 insulin-like antagonist, INS-37, which promotes the nuclear localization of intestinal HLH-30/TFEB, a key pro-longevity regulator. Mating induces the agonist INS-8, promoting HLH-30 nuclear exit and subsequent death. In opposition to the protective role of HLH-30 and DAF-16/FOXO, TOR/LET-363 and the IIS-regulated Zn-finger transcription factor PQM-1 promote seminal-fluid-induced killing. Self-sperm maintenance of nuclear HLH-30/TFEB allows hermaphrodites to resist mating-induced death until self-sperm are exhausted, increasing the chances that mothers will survive through reproduction. Mothers combat males' hijacking of their IIS pathway by expressing an insulin antagonist that keeps her healthy through the activity of pro-longevity factors, as long as she has her own sperm to utilize. Keywords Animals, Caenorhabditis elegans, Signal Transduction, Female, Male, Sexual Behavior, Animal, TOR Serine-Threonine Kinases, Caenorhabditis elegans Proteins, Insulin, Longevity, Peptides, Reproduction, Basic Helix-Loop-Helix Transcription Factors, Disorders of Sex Development Journal Elife Volume 8 Date Published 2019 Jul 08 ISSN Number 2050-084X DOI 10.7554/eLife.46413 Alternate Journal Elife PMCID PMC6697448 PMID 31282862 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML