Graduate School of Frontier Biosciences, Osaka University

Japanese

Suppression of autophagic activity by Rubicon is a signature of aging

Journal Nat Commun 10, 847 (2019)
Authors Nakamura S (1, 2, 3), Oba M (4, 5), Suzuki M (4), Takahashi A (6), Yamamuro T (1), Fujiwara M (1), Ikenaka K (7), Minami S (6), Tabata N (8, 9, 10), Yamamoto K (11), Kubo S (1, 2), Tokumura A (1), Akamatsu K (1), Miyazaki Y (1, 2), Kawabata T (1, 12), Hamasaki M (1, 2), Fukui K (5), Sango K (4), Watanabe Y (13), Takabatake Y (3), Kitajima TS (8, 9, 10), Okada Y (11), Mochizuki H (7), Isaka Y (6), Antebi A (14, 15), Yoshimori T (16, 17)
  1. Department of Genetics, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
  2. Department of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka, 565-0871, Japan.
  3. Institute for Advanced Co-Creation Studies, Osaka University, Osaka, 565-0871, Japan.
  4. Diabetic Neuropathy Project, Department of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, 156-8506, Japan.
  5. Department of Bioscience and Engineering, Shibaura Institute of Technology, Saitama, 337-8570, Japan.
  6. Department of Nephrology, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
  7. Department of Neurology, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
  8. Laboratory for Chromosome Segregation, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, 650-0047, Japan.
  9. Laboratory of Molecular Cell Biology and Development, Graduate School of Biostudies, Kyoto University, Kyoto, 606-8501, Japan.
  10. Laboratory of Biomolecular Informatics, Graduate School of Science, Osaka University, Osaka, 560-0043, Japan.
  11. Department of Statistical Genetics, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
  12. Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, 852-8523, Japan.
  13. Department of Basic Geriatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
  14. Department of Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Cologne, 50931, Germany.
  15. Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Cologne, 50931, Germany.
  16. Department of Genetics, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan. tamyoshi@fbs.osaka-u.ac.jp.
  17. Department of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka, 565-0871, Japan. tamyoshi@fbs.osaka-u.ac.jp.
Title Suppression of autophagic activity by Rubicon is a signature of aging
PubMed 30783089
Laboratory Laboratory of Intracellular Membrane Dynamics 〈Prof. Yoshimori〉
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.