Metabolic Rate Regulates L1 Longevity in C. elegans

Inhwan Lee,Jeongho Kim,Amber Hendrix,Jennifer Yoshimoto,Young-Jai You,Patrick Callaerts

doi:10.1371/journal.pone.0044720

Inhwan Lee, Jeongho Kim + Show 4 more

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https://doi.org/10.1371/journal.pone.0044720

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Abstract

Animals have to cope with starvation. The molecular mechanisms by which animals survive long-term starvation, however, are not clearly understood. When they hatch without food, C. elegans arrests development at the first larval stage (L1) and survives more than two weeks. Here we show that the survival span of arrested L1s, which we call L1 longevity, is a starvation response regulated by metabolic rate during starvation. A high rate of metabolism shortens the L1 survival span, whereas a low rate of metabolism lengthens it. The longer worms are starved, the slower they grow once they are fed, suggesting that L1 arrest has metabolic costs. Furthermore, mutants of genes that regulate metabolism show altered L1 longevity. Among them, we found that AMP-dependent protein kinase (AMPK), as a key energy sensor, regulates L1 longevity by regulating this metabolic arrest. Our results suggest that L1 longevity is determined by metabolic rate and that AMPK as a master regulator of metabolism controls this arrest so that the animals survive long-term starvation.

Highlights

In nature, animals often face long-term starvation without knowing when the meal will be
AMP-dependent protein kinase (AMPK) regulates metabolism in a low energy state such as starvation, we focused on L1 longevity of aak-2 mutants. aak-1 and aak-2 are two C. elegans genes encoding AMPK a subunits
Recent studies show that L1 arrest is regulated by the insulin pathway and that it is an active process of responding to stress during which worms are prepared for growth once food becomes available [1,17]

Summary

Introduction

Animals often face long-term starvation without knowing when the meal will be. When hatched in the absence of food, the first stage larvae (L1s) of C. elegans survive starvation for approximately two weeks. This arrest, called L1 diapause, is distinct from another form of developmental arrest called dauer diapause that occurs at a stage equivalent to the third-stage larva (L3). Whereas the molecular mechanisms of dauer diapause have been intensively studied, those of L1 diapause have not It has been shown, that L1 arrest requires reduced insulin signaling [1,2], suggesting metabolic rate might be a crucial factor to survive starvation during L1 arrest

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