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Suppression of autophagic activity by Rubicon is a signature of aging

Author

Listed:
  • Shuhei Nakamura

    (Osaka University
    Osaka University
    Osaka University)

  • Masaki Oba

    (Tokyo Metropolitan Institute of Medical Science, Setagaya
    Shibaura Institute of Technology)

  • 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)
    Kyoto University
    Osaka University)

  • Kenichi Yamamoto

    (Osaka University)

  • Sayaka Kubo

    (Osaka University
    Osaka University)

  • Ayaka Tokumura

    (Osaka University)

  • Kanako Akamatsu

    (Osaka University)

  • Yumi Miyazaki

    (Osaka University
    Osaka University)

  • Tsuyoshi Kawabata

    (Osaka University
    Nagasaki University)

  • Maho Hamasaki

    (Osaka University
    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)
    Kyoto University
    Osaka University)

  • 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
    University of Cologne)

  • Tamotsu Yoshimori

    (Osaka University
    Osaka University)

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.

Suggested Citation

  • Shuhei Nakamura & Masaki Oba & Mari Suzuki & Atsushi Takahashi & Tadashi Yamamuro & Mari Fujiwara & Kensuke Ikenaka & Satoshi Minami & Namine Tabata & Kenichi Yamamoto & Sayaka Kubo & Ayaka Tokumura &, 2019. "Suppression of autophagic activity by Rubicon is a signature of aging," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08729-6
    DOI: 10.1038/s41467-019-08729-6
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    Cited by:

    1. Áron Szabó & Virág Vincze & Aishwarya Sanjay Chhatre & András Jipa & Sarolta Bognár & Katalin Eszter Varga & Poulami Banik & Adél Harmatos-Ürmösi & Lukas J. Neukomm & Gábor Juhász, 2023. "LC3-associated phagocytosis promotes glial degradation of axon debris after injury in Drosophila models," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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