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

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

iScience. 2021 Jun 10;24(7):102706. doi: 10.1016/j.isci.2021.102706. eCollection 2021 Jul 23.

Authors

Masaharu Uno^{1

2}, Yuri Tani², Masanori Nono^{1

2}, Emiko Okabe^{1

2}, Saya Kishimoto^{1

2}, Chika Takahashi^{1

2}, Ryoji Abe², Takuya Kurihara², Eisuke Nishida^{1

2}

Affiliations

¹ RIKEN Center for Biosystems Dynamics Research (BDR), Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
² Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.

Abstract

Previous 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.

Keywords: Biological sciences; Cell biology; Genetics.