Suppression of autophagic activity by Rubicon is a signature of aging
Journal | Nat Commun 10, 847 (2019) |
---|---|
Title | Suppression of autophagic activity by Rubicon is a signature of aging |
Laboratory | Laboratory of Intracellular Membrane Dynamics |
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.
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 (1, 2)
|
---|---|
PubMed | 30783089 |