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.
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Strains were provided by the Caenorhabditis Genetics Center. This work was supported by NIH grant R01AG038518 to MK and NIH grant K99AG045200 to SFL. SFL was supported by NIH Training Grant T32AG000057. SFL was also supported by an AFAR post-doctoral fellowship. Additional support was provided by the UW Healthy Aging and Longevity Research Institute, the UW Nathan Shock Center of Excellence in the Basic Biology of Aging (NIH grant P30AG013280), and an award to MK from the M. J. Murdock Charitable Trust.
SFL, GJ, and MK designed the experiments. SFL, GJ, MP, GLS, JD, AL, and MF performed the experiments. SFL, GJ, and MK analyzed the experiments. SFL, GJ, and MK wrote the paper.
Scott F. Leiser and Gholamali Jafari contributed equally to this work.
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Leiser, S.F., Jafari, G., Primitivo, M. et al. Age-associated vulval integrity is an important marker of nematode healthspan. AGE 38, 419–431 (2016). https://doi.org/10.1007/s11357-016-9936-8
- C. elegans