piRNAs regulate a Hedgehog germline-to-soma pro-aging signal

Cheng Shi, Coleen T. Murphy

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)47-63
Number of pages17
JournalNature Aging
Issue number1
StatePublished - Jan 2023

All Science Journal Classification (ASJC) codes

  • Geriatrics and Gerontology
  • Aging
  • Neuroscience (miscellaneous)


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