Delayed development and lifespan extension as features of metabolic lifestyle alteration in C. elegans under dietary restriction.
2006
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.
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