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
Affiliations
Masaharu Uno
RIKEN Center for Biosystems Dynamics Research (BDR), Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan; Corresponding author
Yuri Tani
Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
Masanori Nono
RIKEN Center for Biosystems Dynamics Research (BDR), Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
Emiko Okabe
RIKEN Center for Biosystems Dynamics Research (BDR), Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
Saya Kishimoto
RIKEN Center for Biosystems Dynamics Research (BDR), Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
Chika Takahashi
RIKEN Center for Biosystems Dynamics Research (BDR), Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
Ryoji Abe
Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
Takuya Kurihara
Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
Eisuke Nishida
RIKEN Center for Biosystems Dynamics Research (BDR), Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan; Corresponding author
Summary: 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.
