Neuronal DAF-16-to-intestinal DAF-16 communication underlies organismal lifespan extension in C. elegans

Masaharu Uno,Yuri Tani,Masanori Nono,Emiko Okabe,Saya Kishimoto,Chika Takahashi,Ryoji Abe,Takuya Kurihara,Eisuke Nishida

doi:10.1016/j.isci.2021.102706

Abstract

SummaryPrevious studies have revealed the importance of inter-tissue communications for lifespan regulation. However, the inter-tissue network responsible for lifespan regulation is not well understood, even in a simple organism Caenorhabditis elegans. To understand the mechanisms underlying systemic lifespan regulation, we focused on lifespan regulation by the insulin/insulin-like growth factor-1 signaling (IIS) pathway; IIS reduction activates the DAF-16/FOXO transcription factor, which results in lifespan extension. Our tissue-specific knockdown and knockout analyses demonstrated that IIS reduction in neurons and the intestine markedly extended lifespan. DAF-16 activation in neurons resulted in DAF-16 activation in the intestine and vice versa. Our dual gene manipulation method revealed that intestinal and neuronal DAF-16 mediate longevity induced by daf-2 knockout in neurons and the intestine, respectively. In addition, the systemic regulation of intestinal DAF-16 required the IIS pathway in intestinal and neurons. Collectively, these results highlight the importance of the neuronal DAF-16-to-intestinal DAF-16 communication for organismal lifespan regulation.

Highlights

As organisms developed multicellularity, those with specialized cells, tissues, and organs emerged during evolution
To understand the mechanisms underlying systemic lifespan regulation, we focused on lifespan regulation by the insulin/insulin-like growth factor-1 signaling (IIS) pathway; IIS reduction activates the DAF-16/FOXO transcription factor, which results in lifespan extension
The systemic regulation of intestinal DAF-16 required the IIS pathway in intestinal and neurons. These results highlight the importance of the neuronal DAF-16-to-intestinal DAF16 communication for organismal lifespan regulation

Summary

Introduction

Those with specialized cells, tissues, and organs emerged during evolution. To achieve systemic regulation in multicellular organisms with specialized tissues, inter-tissue communication systems evolved. The central nervous system influences many tissue behaviors via hormones or neurons. Recent studies have suggested that tissues other than those in the nervous system can regulate other tissues involved in many biological processes (Moskalev, 2015). The examination of inter-tissue communications is the key to understanding the behavior of multicellular organisms. Recent studies have shown that aging is regulated in a systemic fashion (Taylor and Dillin, 2013; Leiser et al, 2015; Burkewitz et al, 2015; Durieux et al, 2011), the inter-tissue communications underlying lifespan regulation remain largely unknown

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