2. Academic Validation
  3. [Gly14]-Humanin ameliorates high glucose-induced endothelial senescence via SIRT6

[Gly14]-Humanin ameliorates high glucose-induced endothelial senescence via SIRT6

  • Sci Rep. 2024 Dec 28;14(1):30924. doi: 10.1038/s41598-024-81878-x.
Muqin Li # 1 2 3,  Zhihua Liu # 1,  Xueqin Cao # 4,  Wenjin Xiao 1,  Shurong Wang 1,  Chengyuan Zhao 1 5,  Ying Zhao 6,  Ying Xie 7
Affiliations

Affiliations

  • 1 Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
  • 2 Department of Endocrinology, The First People's Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, 222061, JiangSu, China.
  • 3 Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, 215004, China.
  • 4 Department of Endocrinology, The Fourth Affiliated Hospital of Soochow University, Chongwen Road No. 9, Suzhou, 215000, Jiangsu, China.
  • 5 Department of endocrinology, Taizhou school of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Nanjing Medical University, 366 Taihu Road, Taizhou, 225300, China.
  • 6 Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Soochow Medical College of Soochow University, Suzhou, 215123, China. yzhao@suda.edu.cn.
  • 7 Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. 13013883877@126.com.
  • # Contributed equally.
PMID: 39730568 DOI: 10.1038/s41598-024-81878-x
Abstract

High glucose (HG) induced endothelial senescence is related to endothelial dysfunction and cardiovascular complications in diabetic patients. Humanin, a member of mitochondrial derived Peptides (MDPs), is thought to contribute to aging-related cardiovascular protection. The goal of the study is to explore the pathogenesis of HG-induced endothelial senescence and potential anti-senescent effects of Humanin. Human umbilical vein endothelial cells (HUVECs) were exposed to glucose to induce senescence, determined by β-galactosidase staining and the expressions of p21, p53, and p16. A clinically relevant dose of HG (15 mM, HG) induced endothelial senescence after 72 h incubation without elevated Apoptosis. HG-induced senescence was attributed to the induction of Reactive Oxygen Species (ROS) caused by SIRT6 downregulation, as ROS inhibitor N-acetyl cysteine blocked HG-induced senescence, while inactivation of SIRT6 increased ROS levels and promoted senescence. Strikingly. pretreatment with [Gly14]-Humanin (HNG) antagonized the downregulation of SIRT6 in response to HG and alleviated ROS production and cell senescence. HG-induced reduction of SIRT6 results in ROS overproduction and endothelial senescence. Humanin protects against HG-induced endothelial senescence via SIRT6. This study provides new directions for biological products related to Humanin to be a potential candidate for the prevention of vascular aging in diabetes.

Keywords

Endothelial cells; Humanin; Reactive oxygen species; SIRT6; Senescence.

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