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Cysteine protease ATG4D (EC 3.4.22.-) (AUT-like 4 cysteine endopeptidase) (Autophagin-4) (Autophagy-related cysteine endopeptidase 4) (Autophagy-related protein 4 homolog D) [Contains: Cysteine protease ATG4D, mitochondrial] [APG4D] [AUTL4]


Reduction of Aging-Induced Oxidative Stress and Activation of Autophagy by Bilberry Anthocyanin Supplementation via the AMPK-mTOR Signaling Pathway in Aged Female Rats.

Oxidative-stress-induced senescence constitutes a great risk factor for chronic diseases. Therefore, ameliorating oxidative-stress-induced senescence is expected to prevent chronic diseases. The beneficial effects of bilberry anthocyanin (BA) on healthy aging were evaluated using 12 month old, aging female SD rats in this study. The experimental results suggested that consumption of a middle-dose of BA (MBA) appreciably increased the relative liver mass by 7.34% when compared with that of the AC group. Furthermore, BA significantly increased the total antioxidant capacity, total superoxide dismutase activity, and catalase activities; decreased malondialdehyde, serum low-density lipoprotein cholesterol (LDL-C), serum total cholesterol (TC), serum triglyceride (TG), and glycated serum protein (GSP) levels; and reduced TC/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratios. In addition, MBA decreased the activity of fecal bacterial enzymes and increased the content of fecal short-chain fatty acids. The Western blot results showed that MBA significantly upregulated the expression of OCLN, ZO-1, and autophagy-related proteins (ATP6 V0C, ATG4D, and CTSB) in aging rats. Moreover, it also showed that MBA induced the phosphorylation of AMPK and FOXO3a and inhibited the phosphorylation of mTOR, which indicated that bilberry anthocyanin induced autophagy via the AMPK-mTOR signaling pathways. This induction of autophagy further promoted oxidative stress resistance effects and intestinal epithelial barrier function of bilberry anthocyanin in aging female rats.

MeSH Terms

  • AMP-Activated Protein Kinases
  • Aging
  • Animals
  • Anthocyanins
  • Autophagy
  • Dietary Supplements
  • Female
  • Forkhead Box Protein O3
  • Humans
  • Lipoproteins, LDL
  • Malondialdehyde
  • Oxidative Stress
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • TOR Serine-Threonine Kinases
  • Triglycerides
  • Vaccinium myrtillus


  • aging female rats
  • autophagy
  • bilberry anthocyanin
  • intestinal epithelial barrier