Suppression of autophagic activity by Rubicon is a signature of aging

Nat Commun. 2019 Feb 19;10(1):847. doi: 10.1038/s41467-019-08729-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Aging / physiology*
  • Animals
  • Animals, Genetically Modified
  • Autophagy / genetics
  • Autophagy / physiology*
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Drosophila / genetics
  • Drosophila / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Female
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Longevity
  • Male
  • Mice, Inbred C57BL

Substances

  • Autophagy-Related Proteins
  • Caenorhabditis elegans Proteins
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Rubicon protein, Drosophila
  • Y56A3A.16 protein, C elegans
  • rubicon protein, mouse