2. Academic Validation
  3. Calcium transferring from ER to mitochondria via miR-129/ITPR2 axis controls cellular senescence in vitro and in vivo

Calcium transferring from ER to mitochondria via miR-129/ITPR2 axis controls cellular senescence in vitro and in vivo

  • Mech Ageing Dev. 2024 Jan 11:111902. doi: 10.1016/j.mad.2024.111902.
Yue Gao 1,  Lei Xu 2,  Yaru Li 2,  Dandan Qi 2,  Chaofan Wang 2,  Changjiao Luan 3,  Shihui Zheng 4,  Qiu Du 2,  Weili Liu 2,  Guotao Lu 5,  Weijuan Gong 6,  Xingjie Ma 7
Affiliations

Affiliations

  • 1 Department of The Central Laboratory, Department of Intensive Care, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China; Department of Pathology, Northern Jiangsu People's Hospital, Yangzhou, China.
  • 2 Department of The Central Laboratory, Department of Intensive Care, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
  • 3 Department of The Central Laboratory, Department of Intensive Care, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China; Department of Lung, The Third People's Hospital of Yangzhou, Yangzhou, China.
  • 4 Department of Molecular Biology, Inter faculty Institute of Cell Biology, Eberhard Karls University Tuebingen, Tuebingen, Germany.
  • 5 Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
  • 6 Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. Electronic address: wjgong@yzu.edu.cn.
  • 7 Department of The Central Laboratory, Department of Intensive Care, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. Electronic address: xingjie.ma@yzu.edu.cn.
PMID: 38218462 DOI: 10.1016/j.mad.2024.111902
Abstract

Senescent cells are known to be accumulated in aged organisms. Although the two main characteristics, cell cycle arrest (for dividing cells) and secretion of senescence-associated secretory phenotype (SASP) factors, have been well described, the lack of sufficient senescent markers and incomplete understanding of mechanisms have limited the progress of the anti-senescence field. Calcium transferred from the endoplasmic reticulum (ER) via inositol 1, 4, 5-trisphosphate receptor type 2 (ITPR2) to mitochondria has emerged as a key player during cellular senescence and aging. However, the internal regulatory mechanisms, particularly those of endogenous molecules, remain only partially understood. Here we identified miRNA-129 (miR-129) as a direct repressor of ITPR2. Interestingly, miR-129 controlled a cascade of intracellular calcium signaling, mitochondrial membrane potential (MMP), Reactive Oxygen Species (ROS), DNA damage, and consequently cellular senescence through ITPR2 and mitochondrial calcium uniporter (MCU). In addition, miR-129 was repressed in different senescence models and delayed bleomycin-induced cellular senescence. Importantly, intraperitoneal injection of miR-129 partly postponed bleomycin-accelerated lung aging and natural aging markers as well as reduced immunosenescence markers in mice. Altogether, these findings demonstrated that miR-129 regulated cellular senescence and aging markers via intracellular calcium signaling by directly targeting ITPR2.

Keywords

ITPR2; MCU; calcium signaling; cellular senescence; miR-129.

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