title: Age-associated vulval integrity is an important marker of nematode healthspan.
abstract: Improving healthspan, defined as the period where organisms live without frailty and/or disease, is a major goal of biomedical research. While healthspan measures in people are relatively easy to identify, developing robust markers of healthspan in model organisms has proven challenging. Studies using the nematode Caenorhabditis elegans have provided vital information on the basic mechanisms of aging; however, worm health is difficult to define, and the impact of interventions that increase lifespan on worm healthspan has been controversial. Here, we describe a marker of population healthspan in C. elegans that we term age-associated vulval integrity defects, or Avid, frequently described elsewhere as rupture or exploding. We connect the presence of this phenotype with temperature, reproduction, diet, and longevity. Our results show that Avid occurs in post-reproductive worms under common laboratory conditions at a frequency that correlates negatively with temperature; Avid is rare in worms kept at 25 °C and more frequent in worms kept at 15 °C. We describe the kinetics of Avid, link the phenotype to oocyte production, and describe how Avid involves the ejection of worm proteins and/or internal organ(s) from the vulva. Finally, we find that Avid is preventable by removing worms from food, suggesting that Avid results from the intake, digestion, and/or absorption of food. Our results show that Avid is a significant cause of death in worm populations maintained under laboratory conditions and that its prevention often correlates with worm longevity. We propose that Avid is a powerful marker of worm healthspan whose underlying molecular mechanisms may be conserved.
authors: Department of Pathology, University of Washington, Seattle, WA, 98195, USA. sleiser@uw.edu.
authors: Scott F
authors: SF
authors: Leiser
authors: Department of Pathology, University of Washington, Seattle, WA, 98195, USA.
authors: Gholamali
authors: G
authors: Jafari
authors: Department of Pathology, University of Washington, Seattle, WA, 98195, USA.
authors: Melissa
authors: M
authors: Primitivo
authors: Department of Pathology, University of Washington, Seattle, WA, 98195, USA.
authors: George L
authors: GL
authors: Sutphin
authors: Department of Pathology, University of Washington, Seattle, WA, 98195, USA.
authors: Jingyi
authors: J
authors: Dong
authors: Department of Pathology, University of Washington, Seattle, WA, 98195, USA.
authors: Alison
authors: A
authors: Leonard
authors: Department of Pathology, University of Washington, Seattle, WA, 98195, USA.
authors: Marissa
authors: M
authors: Fletcher
authors: Department of Pathology, University of Washington, Seattle, WA, 98195, USA. kaeber@uw.edu.
authors: Matt
authors: M
authors: Kaeberlein
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D004032:Diet; D005260:Female; D006262:Health; D008136:Longevity; D009154:Mutation / Q000235:genetics; D009865:Oocytes / Q000378:metabolism; D010641:Phenotype; D012098:Reproduction; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics; D014844:Vulva / Q000473:pathology*
chemical_list: D029742:Caenorhabditis elegans Proteins; C541178:HIF-1 protein, C elegans; D014157:Transcription Factors
keywords: C. elegans; Healthspan; Longevity; Reproduction; Rupture; Temperature