Nakamura, Shuhei ORCID: 0000-0002-1488-8317, Oba, Masaki, Suzuki, Mari, Takahashi, Atsushi, Yamamuro, Tadashi ORCID: 0000-0002-0610-5204, Fujiwara, Mari, Ikenaka, Kensuke, Minami, Satoshi, Tabata, Namine, Yamamoto, Kenichi, Kubo, Sayaka, Tokumura, Ayaka, Akamatsu, Kanako, Miyazaki, Yumi, Kawabata, Tsuyoshi, Hamasaki, Maho, Fukui, Koji ORCID: 0000-0003-2748-3228, Sango, Kazunori, Watanabe, Yoshihisa, Takabatake, Yoshitsugu, Kitajima, Tomoya S., Okada, Yukinori, Mochizuki, Hideki, Isaka, Yoshitaka, Antebi, Adam and Yoshimori, Tamotsu (2019). Suppression of autophagic activity by Rubicon is a signature of aging. Nat. Commun., 10. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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 a-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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Nakamura, ShuheiUNSPECIFIEDorcid.org/0000-0002-1488-8317UNSPECIFIED
Oba, MasakiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suzuki, MariUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Takahashi, AtsushiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yamamuro, TadashiUNSPECIFIEDorcid.org/0000-0002-0610-5204UNSPECIFIED
Fujiwara, MariUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ikenaka, KensukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Minami, SatoshiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tabata, NamineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yamamoto, KenichiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kubo, SayakaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tokumura, AyakaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Akamatsu, KanakoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Miyazaki, YumiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kawabata, TsuyoshiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamasaki, MahoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fukui, KojiUNSPECIFIEDorcid.org/0000-0003-2748-3228UNSPECIFIED
Sango, KazunoriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Watanabe, YoshihisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Takabatake, YoshitsuguUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kitajima, Tomoya S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Okada, YukinoriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mochizuki, HidekiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Isaka, YoshitakaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antebi, AdamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yoshimori, TamotsuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-156468
DOI: 10.1038/s41467-019-08729-6
Journal or Publication Title: Nat. Commun.
Volume: 10
Date: 2019
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LIFE-SPAN EXTENSION; ALPHA-SYNUCLEIN; CAENORHABDITIS-ELEGANS; LIPID-METABOLISM; LONGEVITY; MITOPHAGY; RAPAMYCIN; CELLS; LIVER; NEURODEGENERATIONMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15646

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