Sleep Counteracts Aging Phenotypes to Survive Starvation-Induced Developmental Arrest in C. elegans

Abstract

SummarySleep is ancient and fulfills higher brain functions as well as basic vital processes. Little is known about how sleep emerged in evolution and what essential functions it was selected for. Here, we investigated sleep in Caenorhabditis elegans across developmental stages and physiological conditions to find out when and how sleep in a simple animal becomes essential for survival. We found that sleep in worms occurs during most stages and physiological conditions and is typically induced by the sleep-active RIS neuron. Food quality and availability determine sleep amount. Extended starvation, which induces developmental arrest in larvae, presents a major sleep trigger. Conserved nutrient-sensing regulators of longevity and developmental arrest, AMP-activated kinase and FoxO, act in parallel to induce sleep during extended food deprivation. These metabolic factors can act in multiple tissues to signal starvation to RIS. Although sleep does not appear to be essential for a normal adult lifespan, it is crucial for survival of starvation-induced developmental arrest in larvae. Rather than merely saving energy for later use, sleep counteracts the progression of aging phenotypes, perhaps by allocating resources. Thus, sleep presents a protective anti-aging program that is induced by nutrient-sensing longevity pathways to survive starvation-induced developmental arrest. All organisms are threatened with the possibility of experienced famine in their life, which suggests that the molecular coupling of starvation, development, aging, and sleep was selected for early in the evolution of nervous systems and may be conserved in other species, including humans.

Prolonged quiescence delays somatic stem cell‐like divisions in Caenorhabditis elegans and is controlled by insulin signaling

“…It is also important to notice that insulin signaling has already been connected to the progression of L1 aging through the regulation of sleep. However, daf‐16 mutation alone does not impair L1 sleep (Wu et al, ), and therefore, sleep loss could not explain the defective recovery of this mutant.…”

“…However, extended L1 arrest reduces the potential for recovery (Roux, Langhans, Huynh, & Kenyon, 2016). Sleep during L1 arrest counteracts aging phenotypes and increases survival rates (Wu, Masurat, Preis, & Bringmann, 2018). Thus, the nematode offers an exceptional tractable model system to study the mechanisms that impact cell arrest and proliferation in a multicellular organism.…”

Genetic sleep deprivation: using sleep mutants to study sleep functions

“…One of the strongest mutations in Drosophila is sleepless with > 80% sleep reduction [105]. Caenorhabditis elegans physiological sleep during lethargus is reduced by about 80% in hyperactive mutants (egl-30gf [127] or acy-1gf [128]) as well as in ALA mutant ceh-17(À) (locomotion quiescence 20 min after heat shock) [35] and is virtually abolished across several physiological conditions (reduction here displayed as 99%) by aptf-1 À/À or ablation of the sleep-active RIS neuron [124,134,139].…”

“…Sleep bouts become undetectable in these “RIS mutants” during many life stages and physiological conditions. aptf‐1 mutant worms show no severe hyperactivity during wake, indicating that they are not strongly hyperaroused following sleep loss and that sleep loss is likely not a consequence of increased arousal . Thus, during many physiological conditions, RIS inactivation in C. elegans presents both a virtually complete as well as a highly specific model for sleeplessness (Fig ).…”

“…Sleep time fraction varies between 3–20 h/24 h with large herbivores sleeping little and bats sleeping a lot . Model organisms fall within the range of wild species .…”