Delayed development and lifespan extension as features of metabolic lifestyle alteration inC. elegansunder dietary restriction

Abstract

SUMMARY Studies of the model organism Caenorhabditis elegans have almost exclusively utilized growth on a bacterial diet. Such culturing presents a challenge to automation of experimentation and introduces bacterial metabolism as a secondary concern in drug and environmental toxicology studies. Axenic cultivation of C. elegans can avoid these problems, yet past work suggests that axenic growth is unhealthy for C. elegans. Here we employ a chemically defined liquid medium to culture C. elegans and find development slows, fecundity declines, lifespan increases, lipid and protein stores decrease, and gene expression changes relative to that on a bacterial diet. These changes do not appear to be random pathologies associated with malnutrition, as there are no developmental delays associated with starvation, such as L1 or dauer diapause. Additionally, development and reproductive period are fixed percentages of lifespan regardless of diet,suggesting that these alterations are adaptive. We propose that C. elegans can exist as a healthy animal with at least two distinct adult life histories. One life history maximizes the intrinsic rate of population increase, the other maximizes the efficiency of exploitation of the carrying capacity of the environment. Microarray analysis reveals increased transcript levels of daf-16 and downstream targets and past experiments demonstrate that DAF-16 (FOXO) acting on downstream targets can influence all of the phenotypes we see altered in maintenance medium. Thus, life history alteration in response to diet may be modulated by DAF-16. Our observations introduce a powerful system for automation of experimentation on healthy C. elegans and for systematic analysis of the profound impact of diet on animal physiology.

A size threshold governsCaenorhabditis elegansdevelopmental progression

“…One interesting possibility is that the properties of the collagenrich cuticle, which encases the growing cells and tissues of the worm, give rise to an upper worm size limit, providing a mechanosensory cue for moulting. Consistent with this, at each moult the cuticular sheath is about the same length regardless of growth temperature [44]. In M. sexta, tracheal size limits oxygen intake due to its saltational growth, thus contributing to the requirement for moulting [16].…”

TMC-1 attenuates C. elegans development and sexual behaviour in a chemically defined food environment

“…A commonly studied stress is dietary restriction, which can slow down/arrest development and reduce sexual behaviour 12,55 . In contrast to dietary restriction, where nutrients are limited, the synthetic CeMM food contains the basic nutrients in excess.…”

“…In contrast to dietary restriction, where nutrients are limited, the synthetic CeMM food contains the basic nutrients in excess. However, since others have reported that C. elegans superficially responds to CeMM similarly to dietary restriction 12 , the stress that the animal experiences might be related to the suboptimal presentation of the nutrients and the low efficiency of nutrient utilization. Although the population growth is slower in CeMM compared with a bacterial diet 10 , the population will eventually grow to high density.…”

Feeding a ROS-generator to Caenorhabditis elegans leads to increased expression of small heat shock protein HSP-16.2 and hormesis

“…So far, however, studies in C. elegans have almost exclusively utilized feeding regimes in which animals are kept on agar plates with an E. coli lawn. Metabolism of supplied nutrients or nonnutritional components by the bacteria and production of mainly unknown metabolites that might contribute to the biological effects of a dietary ingredient is a concern [33]. The use of liquid axenic media on the other hand produce phenotypic changes in development, fecundity, lifespan and metabolism when compared to the apparent ''gold standard'' of feeding bacteria [10,33].…”