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

Nat Commun. 2014 Sep 11:5:4879. doi: 10.1038/ncomms5879.

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 Δ(7)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Caloric Restriction*
  • Cholestenes / metabolism*
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism
  • Gene Expression Regulation, Developmental
  • Germ Cells / metabolism*
  • Longevity / genetics*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Signal Transduction

Substances

  • Caenorhabditis elegans Proteins
  • Cholestenes
  • Receptors, Cytoplasmic and Nuclear
  • delta7-dafachronic acid
  • nhr-8 protein, C-elegans
  • Cytochrome P-450 Enzyme System
  • DAF-9 protein, C elegans
  • Phosphotransferases (Alcohol Group Acceptor)
  • let-363 protein, C elegans