Two forms of death in ageing Caenorhabditis elegans

Abstract

Ageing generates senescent pathologies, some of which cause death. Interventions that delay or prevent lethal pathologies will extend lifespan. Here we identify life-limiting pathologies in Caenorhabditis elegans with a necropsy analysis of worms that have died of old age. Our results imply the presence of multiple causes of death. Specifically, we identify two classes of corpse: early deaths with a swollen pharynx (which we call ‘P deaths'), and later deaths with an atrophied pharynx (termed ‘p deaths'). The effects of interventions on lifespan can be broken down into changes in the frequency and/or timing of either form of death. For example, glp-1 mutation only delays p death, while eat-2 mutation reduces P death. Combining pathology and mortality analysis allows mortality profiles to be deconvolved, providing biological meaning to complex survival and mortality profiles.

Age‐dependent changes and biomarkers of aging in Caenorhabditis elegans

“…Furthermore, sarcomeres in the body wall muscles lose their densely packed structures and regular orientations with increasing age (Glenn et al, ; Herndon et al, ). The C. elegans pharynx, a neuromuscular organ composed of 20 muscle cells and 20 neurons, also loses its integrity during aging (Albertson & Thomson, ; Chow et al, ; Garigan et al, ; Herndon et al, ; Johnston et al, ; Podshivalova, Kerr, & Kenyon, ; Zhao et al, ). In aged worms, the number of myofibrils diminishes and the pharyngeal muscles exhibit an abnormal appearance (Chow et al, ; Garigan et al, ; Herndon et al, ; Podshivalova et al, ; Zhao et al, ).…”

“…The C. elegans pharynx, a neuromuscular organ composed of 20 muscle cells and 20 neurons, also loses its integrity during aging (Albertson & Thomson, ; Chow et al, ; Garigan et al, ; Herndon et al, ; Johnston et al, ; Podshivalova, Kerr, & Kenyon, ; Zhao et al, ). In aged worms, the number of myofibrils diminishes and the pharyngeal muscles exhibit an abnormal appearance (Chow et al, ; Garigan et al, ; Herndon et al, ; Podshivalova et al, ; Zhao et al, ). Other age‐dependent degenerative structural changes, such as darkening of the pharyngeal regions, also occur (Chow et al, ; Garigan et al, ; Herndon et al, ).…”

“…Other age‐dependent degenerative structural changes, such as darkening of the pharyngeal regions, also occur (Chow et al, ; Garigan et al, ; Herndon et al, ). These age‐dependent functional and structural abnormalities of pharyngeal muscles appear to be associated with bacterial accumulation in the terminal bulb of old worms (Podshivalova et al, ; Zhao et al, ). This is consistent with the susceptibility of old worms to infection by pathogenic bacteria, including Pseudomonas aeruginosa (Youngman, Rogers, & Kim, ).…”

“…The motility of worms, as measured by maximum velocity, is prolonged in daf‐2 and eat‐2 mutants compared to wild‐type animals (Hahm et al, ; Huang, Xiong, & Kornfeld, ), although daf‐2 mutants display reduced spontaneous movements for a relatively long time (Bansal, Zhu, Yen, & Tissenbaum, ). Additionally, daf‐2 mutants are resistant to bacterial colonization (Podshivalova et al, ), one of the main causes of early death in C. elegans (Garigan et al, ; Zhao et al, ). Moreover, the reproductive span of daf‐2 and eat‐2 mutant hermaphrodites (Hughes et al, ; Luo et al, ; Luo, Shaw, Ashraf, & Murphy, ) is longer than that of wild‐type worms, although the total number of progeny produced by daf‐2 mutants is reduced (Hughes et al, ).…”

Autophagy-dependent gut-to-yolk biomass conversion generates visceral polymorbidity in agingC. elegans

“…Which of the many extant pathologies limits lifespan may vary between individuals, environmental conditions, genders and species (Fig. 1A, bottom) (Gems 2015;Zhao et al 2017), confounding studies of the genetics of lifespan. We propose that a pathology-focused approach in aging model organisms may yield new insights into the primary mechanism(s) of aging and help understand how genes control lifespan.C.…”