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

研究成果: Article

13 引用 (Scopus)

抜粋

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.

元の言語English
記事番号847
ジャーナルNature Communications
10
発行部数1
DOI
出版物ステータスPublished - 2019 12 1

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ASJC Scopus subject areas

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

これを引用

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., ... 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