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Steroid hormone signalling links reproduction to lifespan in dietary-restricted Caenorhabditis elegans

Author

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  • Manjunatha Thondamal

    (Molecular Biology of the Cell Laboratory, Ecole Normale Supérieure de Lyon—CNRS—Université de Lyon Claude Bernard, UMR5239, 46, Allee d’Italie)

  • Michael Witting

    (Ingolstaedter Landstrasse 1)

  • Philippe Schmitt-Kopplin

    (Ingolstaedter Landstrasse 1)

  • Hugo Aguilaniu

    (Molecular Biology of the Cell Laboratory, Ecole Normale Supérieure de Lyon—CNRS—Université de Lyon Claude Bernard, UMR5239, 46, Allee d’Italie)

Abstract

Dietary restriction (DR) increases healthspan and longevity in many species, including primates, but it is often accompanied by impaired reproductive function. Whether signals associated with the reproductive system contribute to or are required for DR effects on lifespan has not been established. Here we show that expression of the cytochrome P450 DAF-9/CYP450 and production of the steroid hormone Δ7-dafachronic acid (DA) are increased in C. elegans subjected to DR. DA signalling through the non-canonical nuclear hormone receptor NHR-8/NHR and the nutrient-responsive kinase let-363/mTOR is essential for DR-mediated longevity. Steroid signalling also affects germline plasticity in response to nutrient deprivation and this is required to achieve lifespan extension. These data demonstrate that steroid signalling links germline physiology to lifespan when nutrients are limited, and establish a central role for let-363/mTOR in integrating signals derived from nutrients and steroid hormones.

Suggested Citation

  • Manjunatha Thondamal & Michael Witting & Philippe Schmitt-Kopplin & Hugo Aguilaniu, 2014. "Steroid hormone signalling links reproduction to lifespan in dietary-restricted Caenorhabditis elegans," Nature Communications, Nature, vol. 5(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5879
    DOI: 10.1038/ncomms5879
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    Cited by:

    1. Sarah R. Fausett & Asma Sandjak & Bénédicte Billard & Christian Braendle, 2023. "Higher-order epistasis shapes natural variation in germ stem cell niche activity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Shengjie Fan & Yingxuan Yan & Ying Xia & Zhenyu Zhou & Lingling Luo & Mengnan Zhu & Yongli Han & Deqiang Yao & Lijun Zhang & Minglv Fang & Lina Peng & Jing Yu & Ying Liu & Xiaoyan Gao & Huida Guan & H, 2023. "Pregnane X receptor agonist nomilin extends lifespan and healthspan in preclinical models through detoxification functions," Nature Communications, Nature, vol. 14(1), pages 1-23, December.

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