ArticleNature aging2023
piRNAs regulate a Hedgehog germline-to-soma pro-aging signal.
Article in Nature aging, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- Hepatocyte hedgehog signaling controls ferroptosis to alleviate aging-related organ dysfunction.JCI insight · 2026Article
- A Lipocalin and a Hedgehog-related protein are partners in thebioRxiv : the preprint server for biology · 2026Article
- Article
- A transcriptomic resource for glial GABA-associated ASH neuronal aging and candidate pathways.Frontiers in aging neuroscience · 2026Article
- Hedgehog-related genemicroPublication biology · 2026Article
- The Role of PIWI-Interacting RNA in Urologic Carcinoma and Its Clinical Implications.Cancer reports (Hoboken, N.J.) · 2025Review
- Genome-Wide Temporal Gene Expression Reveals a Post-Reproductive Shift in the Nematode Caenorhabditis briggsae.Genome biology and evolution · 2025Article
- Recent progress in regulation of aging by non-coding RNAs inAnimal cells and systems · 2025Review
- A germline-to-soma signal triggers an age-related decline of mitochondrial stress response.Nature communications · 2024Article
- The germline coordinates mitokine signaling.Cell · 2024Article
- Caenorhabditis elegans Hedgehog-related proteins are tissue- and substructure-specific components of the cuticle and precuticle.Genetics · 2024Article
- Somatic piRNA and PIWI-mediated post-transcriptional gene regulation in stem cells and disease.Frontiers in cell and developmental biology · 2024Review
- ThemicroPublication biology · 2024Article
- Decoding lifespan secrets: the role of the gonad inFrontiers in aging · 2024Review
- Ovarian aging in humans: potential strategies for extending reproductive lifespan.GeroScience · 2023Review
- Modulating p38 MAPK signaling by proteostasis mechanisms supports tissue integrity during growth and aging.Nature communications · 2023Article
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2 authors at 2 institutions in 1 country.
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Abstract
The reproductive system regulates somatic aging through competing anti- and pro-aging signals. Germline removal extends somatic lifespan through conserved pathways including insulin and mammalian target-of-rapamycin signaling, while germline hyperactivity shortens lifespan through unknown mechanisms. Here we show that mating-induced germline hyperactivity downregulates piRNAs, in turn desilencing their targets, including the Hedgehog-like ligand-encoding genes wrt-1 and wrt-10, ultimately causing somatic collapse and death. Germline-produced Hedgehog signals require PTR-6 and PTR-16 receptors for mating-induced shrinking and death. Our results reveal an unconventional role of the piRNA pathway in transcriptional regulation of Hedgehog signaling and a new role of Hedgehog signaling in the regulation of longevity and somatic maintenance: Hedgehog signaling is controlled by the tunable piRNA pathway to encode the previously unknown germline-to-soma pro-aging signal. Mating-induced piRNA downregulation in the germline and subsequent Hedgehog signaling to the soma enable the animal to tune somatic resource allocation to germline needs, optimizing reproductive timing and survival.
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