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.

Ancestral roles of the Fam20C family of secreted protein kinases revealed in C. elegans

“…The extrusion through vulva phenotype, observed in ∼30% of famk-1Δ worms (Figs. 1 D and S1 B), indicative of loss of vulval integrity (Reinhart et al, 2000;Leiser et al, 2011Leiser et al, , 2016, was also rescued by psth-1-driven FAMK-1 (0/25 worms analyzed exhibited this phenotype), potentially due to the sth-1 promoter being active in specific vulval cells (Fig. 6 B).…”

Ancestral Roles of the Fam20C Family of Secreted Protein Kinases Revealed by Functional Analysis inC. elegans

“…6 C). The extrusion through vulva phenotype, indicative of loss of vulval integrity (Reinhart et al 2000;Leiser et al 2011;Leiser et al 2016), was also rescued by psth-1-driven FAMK-1 (not shown), potentially due to the sth-1 promoter being active in specific vulval cells ( Fig. 6 A).…”

Optimized criteria for locomotion-based healthspan evaluation in C. elegans using the WorMotel system

“…However, no perfect consensus can be reached on the concept of being 'healthy', as it is an umbrella term covering many facets of quality of life. Several groups have used different physiological parameters to describe health in C. elegans, such as oxidative and heat stress resistance, pharyngeal pumping and autofluorescence [6], vulval integrity [27], intestinal atrophy [28], muscle integrity and yolk production [10]. We here selected daily, stimulated peak activity over daily, stimulated average/median activity as a readout for overall health, as peak values were most robust and less prone to day-to-day activity variations (Fig 5 and S2 Table).…”