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 TakabatakeTomoya S. Kitajima, Yukinori Okada, Hideki Mochizuki, Yoshitaka Isaka, Adam Antebi, Tamotsu Yoshimori

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Article number847
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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worms
Synucleins
Aging of materials
signatures
retarding
Tissue
mice
knockout mice
Neurons
Brain
fibrosis
Animals
phenotype
regulators
kidneys
neurons
organisms
Degradation
brain
animals

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Nakamura, S., Oba, M., Suzuki, M., Takahashi, A., Yamamuro, T., Fujiwara, M., ... Yoshimori, T. (2019). Suppression of autophagic activity by Rubicon is a signature of aging. Nature Communications, 10(1), [847]. https://doi.org/10.1038/s41467-019-08729-6

Suppression of autophagic activity by Rubicon is a signature of aging. / Nakamura, Shuhei; Oba, Masaki; Suzuki, Mari; Takahashi, Atsushi; Yamamuro, Tadashi; Fujiwara, Mari; Ikenaka, Kensuke; Minami, Satoshi; Tabata, Namine; Yamamoto, Kenichi; Kubo, Sayaka; Tokumura, Ayaka; Akamatsu, Kanako; Miyazaki, Yumi; Kawabata, Tsuyoshi; Hamasaki, Maho; Fukui, Koji; Sango, Kazunori; Watanabe, Yoshihisa; Takabatake, Yoshitsugu; Kitajima, Tomoya S.; Okada, Yukinori; Mochizuki, Hideki; Isaka, Yoshitaka; Antebi, Adam; Yoshimori, Tamotsu.

In: Nature Communications, Vol. 10, No. 1, 847, 01.12.2019.

Research output: Contribution to journalArticle

Nakamura, S, Oba, M, Suzuki, M, Takahashi, A, Yamamuro, T, Fujiwara, M, Ikenaka, K, Minami, S, Tabata, N, Yamamoto, K, Kubo, S, Tokumura, A, Akamatsu, K, Miyazaki, Y, Kawabata, T, Hamasaki, M, Fukui, K, Sango, K, Watanabe, Y, Takabatake, Y, Kitajima, TS, Okada, Y, Mochizuki, H, Isaka, Y, Antebi, A & Yoshimori, T 2019, 'Suppression of autophagic activity by Rubicon is a signature of aging', Nature Communications, vol. 10, no. 1, 847. https://doi.org/10.1038/s41467-019-08729-6
Nakamura S, Oba M, Suzuki M, Takahashi A, Yamamuro T, Fujiwara M et al. Suppression of autophagic activity by Rubicon is a signature of aging. Nature Communications. 2019 Dec 1;10(1). 847. https://doi.org/10.1038/s41467-019-08729-6
Nakamura, Shuhei ; Oba, Masaki ; Suzuki, Mari ; Takahashi, Atsushi ; Yamamuro, Tadashi ; Fujiwara, Mari ; Ikenaka, Kensuke ; Minami, Satoshi ; Tabata, Namine ; Yamamoto, Kenichi ; Kubo, Sayaka ; Tokumura, Ayaka ; Akamatsu, Kanako ; Miyazaki, Yumi ; Kawabata, Tsuyoshi ; Hamasaki, Maho ; Fukui, Koji ; Sango, Kazunori ; Watanabe, Yoshihisa ; Takabatake, Yoshitsugu ; Kitajima, Tomoya S. ; Okada, Yukinori ; Mochizuki, Hideki ; Isaka, Yoshitaka ; Antebi, Adam ; Yoshimori, Tamotsu. / Suppression of autophagic activity by Rubicon is a signature of aging. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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