2. Academic Validation
  3. Alginate oligosaccharides enhance autophagy to rejuvenate H2O2-induced senescent IEC-6 through the AMPK/mTOR signaling pathway

Alginate oligosaccharides enhance autophagy to rejuvenate H2O2-induced senescent IEC-6 through the AMPK/mTOR signaling pathway

  • Rejuvenation Res. 2023 Mar 21. doi: 10.1089/rej.2022.0061.
Xinxiu Zhao 1 2,  Shixian Zhou 1 3,  Shunmei Huang 1 4,  Peixia Wang 1 5,  Jie Mou 6,  Caixia Gong 7 8,  Xia Zhang 1 9,  Qin Zhang 1 10,  Yunmei Yang 11 12
Affiliations

Affiliations

  • 1 Zhejiang University School of Medicine First Affiliated Hospital, 71069, Department of Geriatrics, Hangzhou, Zhejiang, China.
  • 2 Zhejiang University School of Medicine First Affiliated Hospital, 71069, Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou, Zhejiang, China; 1514056@zju.edu.cn.
  • 3 Zhejiang University School of Medicine First Affiliated Hospital, 71069, Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou, Zhejiang, China; 1512039@zju.edu.cn.
  • 4 Zhejiang University School of Medicine First Affiliated Hospital, 71069, Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou, Zhejiang, China; hshmfy2005@zju.edu.cn.
  • 5 Zhejiang University School of Medicine First Affiliated Hospital, 71069, Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou, Zhejiang, China; 1513013@zju.edu.cn.
  • 6 The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Department of infectious disease, Chengdu, Sichuan, China; 734106393@qq.com.
  • 7 Zhejiang University School of Medicine First Affiliated Hospital, 71069, Department of Geriatrics , Hangzhou, Zhejiang, China.
  • 8 Zhejiang University School of Medicine First Affiliated Hospital, 71069, Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou, Zhejiang, China; gongcaixia1990@zju.edu.cn.
  • 9 Zhejiang University School of Medicine First Affiliated Hospital, 71069, Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou, Zhejiang, China; zxnjmu@163.com.
  • 10 Zhejiang University School of Medicine First Affiliated Hospital, 71069, Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou, Zhejiang, China; zhangqin1978@zju.edu.cn.
  • 11 Zhejiang University School of Medicine First Affiliated Hospital, 71069, Department of Geriatrics, Hangzhou, China.
  • 12 Zhejiang University School of Medicine First Affiliated Hospital, 71069, Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, Hangzhou, Zhejiang, China; 1194070@zju.edu.cn.
PMID: 36943260 DOI: 10.1089/rej.2022.0061
Abstract

Intestinal aging contributes to the physiological decline of intestine and induces age-associated intestinal diseases. Therefore, the intestine is a vital target to delay intestinal aging and extend healthy lifespan. Alginate oligosaccharides (AOS) have a wide range of biological and pharmacological activities. However, there are no related reports of AOS on intestinal aging. Our study aimed to investigate the effect of AOS on hydrogen peroxide (H2O2)-induced senescent intestinal epithelial cells (IEC-6) and its Anti-aging mechanism. A senescent model was successfully constructed by H2O2 (200 µmol/L) treatment on IEC-6 for 4 h. Different concentrations of AOS (10 µg/mL, 50 µg/mL, 100 µg/mL) were used to intervene in H2O2-induced senescent IEC-6. The number of β-galactosidase staining-positive cells was significantly reduced by AOS intervention. The expression of p21 and p16, known as the senescent biomarkers, was also decreased. In addition, AOS alleviated oxidative stress by reducing ROS and improving anti-oxidative ability. To understand how AOS rejuvenate H2O2-induced senescent IEC-6, we detected the expression level of genes in Autophagy process. The results indicated that AOS restored the expression of Beclin 1, Atg7 and LC3 to enhance Autophagy process by activating AMPK and inhibiting mTOR in H2O2-induced senescent IEC-6. Compound C, an AMPK Inhibitor, abolished the effect of AOS on activating Autophagy and rejuvenating senescent IEC-6. Altogether, our study suggests that AOS is a promising drug for delaying intestinal senescence.

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