Suppression of autophagic activity by Rubicon is a signature of aging

Shuhei Nakamura, Masaki Oba, Mari Suzuki, Atsushi Takahashi, Tadashi Yamamuro, Mari Fujiwara, Kensuke Ikenaka, Satoshi Minami, Namine Tabata, Kenichi Yamamoto, Sayaka Kubo, Ayaka Tokumura, Kanako Akamatsu, Yumi Miyazaki, Tsuyoshi Kawabata, Maho Hamasaki, Koji Fukui, Kazunori Sango, Yoshihisa Watanabe, Yoshitsugu Takabatake, Tomoya S. Kitajima, Yukinori Okada, Hideki Mochizuki, Yoshitaka Isaka, Adam Antebi and Tamotsu Yoshimori ()
Additional contact information
Shuhei Nakamura: Osaka University
Masaki Oba: Tokyo Metropolitan Institute of Medical Science, Setagaya
Mari Suzuki: Tokyo Metropolitan Institute of Medical Science, Setagaya
Atsushi Takahashi: Osaka University
Tadashi Yamamuro: Osaka University
Mari Fujiwara: Osaka University
Kensuke Ikenaka: Graduate School of Medicine, Osaka University
Satoshi Minami: Osaka University
Namine Tabata: RIKEN Center for Biosystems Dynamics Research (BDR)
Kenichi Yamamoto: Osaka University
Sayaka Kubo: Osaka University
Ayaka Tokumura: Osaka University
Kanako Akamatsu: Osaka University
Yumi Miyazaki: Osaka University
Tsuyoshi Kawabata: Osaka University
Maho Hamasaki: Osaka University
Koji Fukui: Shibaura Institute of Technology
Kazunori Sango: Tokyo Metropolitan Institute of Medical Science, Setagaya
Yoshihisa Watanabe: Kyoto Prefectural University of Medicine
Yoshitsugu Takabatake: Osaka University
Tomoya S. Kitajima: RIKEN Center for Biosystems Dynamics Research (BDR)
Yukinori Okada: Osaka University
Hideki Mochizuki: Graduate School of Medicine, Osaka University
Yoshitaka Isaka: Osaka University
Adam Antebi: Max Planck Institute for Biology of Ageing
Tamotsu Yoshimori: Osaka University

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract Autophagy, an evolutionarily conserved cytoplasmic degradation system, has been implicated as a convergent mechanism in various longevity pathways. Autophagic activity decreases with age in several organisms, but the underlying mechanism is unclear. Here, we show that the expression of Rubicon, a negative regulator of autophagy, increases in aged worm, fly and mouse tissues at transcript and/or protein levels, suggesting that an age-dependent increase in Rubicon impairs autophagy over time, and thereby curtails animal healthspan. Consistent with this idea, knockdown of Rubicon extends worm and fly lifespan and ameliorates several age-associated phenotypes. Tissue-specific experiments reveal that Rubicon knockdown in neurons has the greatest effect on lifespan. Rubicon knockout mice exhibits reductions in interstitial fibrosis in kidney and reduced α-synuclein accumulation in the brain. Rubicon is suppressed in several long-lived worms and calorie restricted mice. Taken together, our results suggest that suppression of autophagic activity by Rubicon is one of signatures of aging.

Date: 2019
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DOI: 10.1038/s41467-019-08729-6

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