Suppression of autophagic activity by Rubicon is a signature of aging

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, T. S.; Okada, Y.; Mochizuki, H.; Isaka, Y.; Antebi, A.; Yoshimori, T.

doi:10.1038/s41467-019-08729-6

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Suppression of autophagic activity by Rubicon is a signature of aging

MPS-Authors

/persons/resource/persons50070

Antebi, A.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

External Resource

https://www.ncbi.nlm.nih.gov/pubmed/30783089
(Any fulltext)

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Nakamura, S., Oba, M., Suzuki, M., Takahashi, A., Yamamuro, T., Fujiwara, M., et al. (2019). Suppression of autophagic activity by Rubicon is a signature of aging. Nat Commun, 10(1), 847. doi:10.1038/s41467-019-08729-6.

Cite as: https://hdl.handle.net/21.11116/0000-000B-4202-8

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 alpha-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.