• 作者： Chi-Hsiao Yeh, Zhao-Qing Shen, Tai-Wen Wang, Cheng-Heng Kao, Yuan-Chi Teng, Teng-Kuang Yeh, Chung-Kuang Lu & Ting-Fen Tsai
• 作者服務機構： 1.Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan 2.Center of General Education, Chang Gung University, Taoyuan, Taiwan 3.College of Medicine, Chang Gung University, Taoyuan, Taiwan 4.Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan 5.Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, 155 Li-Nong St., Sec. 2, Peitou, Taipei, 11221, Taiwan 6.Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan 7.Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan 8.Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan 9.National Research Institute of Chinese Medicine, Taipei, Taiwan
• 中文摘要：
• 英文摘要：
  Background: The human CISD2 gene is located within a longevity region mapped on chromosome 4q. In mice,
  Cisd2 levels decrease during natural aging and genetic studies have shown that a high level of Cisd2 prolongs mouse
  lifespan and healthspan. Here, we evaluate the feasibility of using a Cisd2 activator as an efective way of delaying
  aging.
  Methods: Hesperetin was identifed as a promising Cisd2 activator by herb compound library screening. Hesperetin
  has no detectable toxicity based on in vitro and in vivo models. Naturally aged mice fed dietary hesperetin were used
  to investigate the efect of this Cisd2 activator on lifespan prolongation and the amelioration of age-related structural
  defects and functional decline. Tissue-specifc Cisd2 knockout mice were used to study the Cisd2-dependent antiaging efects of hesperetin. RNA sequencing was used to explore the biological efects of hesperetin on aging.
  Results: Three discoveries are pinpointed. Firstly, hesperetin, a promising Cisd2 activator, when orally administered
  late in life, enhances Cisd2 expression and prolongs healthspan in old mice. Secondly, hesperetin functions mainly in a
  Cisd2-dependent manner to ameliorate age-related metabolic decline, body composition changes, glucose dysregu‑
  lation, and organ senescence. Finally, a youthful transcriptome pattern is regained after hesperetin treatment during
  old age.
  Conclusions: Our fndings indicate that a Cisd2 activator, hesperetin, represents a promising and broadly efective
  translational approach to slowing down aging and promoting longevity via the activation of Cisd2.
• 中文關鍵字：
• 英文關鍵字： Longevity, Natural aging, Cisd2, Hesperetin