title: Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans.
abstract: BACKGROUND
  A powerful approach to understanding complex processes such as aging is to use model organisms amenable to genetic manipulation, and to seek relevant phenotypes to measure. Caenorhabditis elegans is particularly suited to studies of aging, since numerous single-gene mutations have been identified that affect its lifespan; it possesses an innate immune system employing evolutionarily conserved signaling pathways affecting longevity. As worms age, bacteria accumulate in the intestinal tract. However, quantitative relationships between worm genotype, lifespan, and intestinal lumen bacterial load have not been examined. We hypothesized that gut immunity is less efficient in older animals, leading to enhanced bacterial accumulation, reducing longevity. To address this question, we evaluated the ability of worms to control bacterial accumulation as a functional marker of intestinal immunity.
  
  
  RESULTS
  We show that as adult worms age, several C. elegans genotypes show diminished capacity to control intestinal bacterial accumulation. We provide evidence that intestinal bacterial load, regulated by gut immunity, is an important causative factor of lifespan determination; the effects are specified by bacterial strain, worm genotype, and biologic age, all acting in concert.
  
  
  CONCLUSIONS
  In total, these studies focus attention on the worm intestine as a locus that influences longevity in the presence of an accumulating bacterial population. Further studies defining the interplay between bacterial species and host immunity in C. elegans may provide insights into the general mechanisms of aging and age-related diseases.
authors.affiliation: Department of Medicine, New York University School of Medicine, NYU Langone Medical Center, 550 First Avenue, OBV A606, New York, NY 10016, USA. portac01@med.nyu.edu
authors.forename: Cynthia
authors.initials: C
authors.lastname: Portal-Celhay
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Bradley
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Blaser
mesh_terms: D000818:Animals; D001419:Bacteria / Q000254:growth & development; D058491:Bacterial Load; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology / Q000382:microbiology* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000276:immunology; D005838:Genotype; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D008136:Longevity; D011972:Receptor, Insulin / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin