Lifespan Extension in C. elegans Caused by Bacterial Colonization of the Intestine and Subsequent Activation of an Innate Immune Response

Dev Cell. 2019 Apr 8;49(1):100-117.e6. doi: 10.1016/j.devcel.2019.03.010.


Mechanisms that control aging are important yet poorly defined. To discover longevity control genes, we performed a forward genetic screen for delayed reproductive aging in C. elegans. Here, we show that am117 is a nonsense mutation in the phm-2 gene, which encodes a protein homologous to human scaffold attachment factor B. phm-2(lf) mutant worms have an abnormal pharynx grinder, which allows live bacteria to accumulate in the intestine. This defect shortens lifespan on highly pathogenic bacteria but extends lifespan and health span on the standard E. coli diet by activating innate immunity pathways that lead to bacterial avoidance behavior and dietary restriction. eat-2(lf) mutants displayed a similar phenotype, indicating accumulation of live bacteria also triggers extended longevity in this mutant. The analysis of phm-2 elucidates connections between pathogen response and aging by defining a mechanism of longevity extension in C. elegans-bacterial colonization, innate immune activation, and bacterial avoidance behavior.

Keywords: C. elegans; SAFB; aging and lifespan; bacterial avoidance; dietary restriction; eat-2; hlh-30; innate immunity; pharynx; phm-2.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / genetics*
  • Aging / immunology
  • Animals
  • Avoidance Learning / physiology
  • Bacteria / immunology
  • Bacteria / pathogenicity
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / immunology
  • Caenorhabditis elegans / microbiology
  • Caenorhabditis elegans Proteins / genetics*
  • Diet
  • Escherichia coli / chemistry
  • Gene Expression Regulation / genetics
  • Host-Pathogen Interactions / genetics
  • Humans
  • Immunity, Innate / genetics
  • Intestines / microbiology
  • Longevity / genetics*
  • Longevity / immunology
  • Receptors, Nicotinic / genetics*


  • Caenorhabditis elegans Proteins
  • Eat-2 protein, C elegans
  • Receptors, Nicotinic
  • phm-2 protein, C elegans