Brito Sofia, Heo Hyojin, Kim Jinyoung, Cha Byungsun, Jeong Youngdo, Choi Wooseon, Shrestha Chandani, Lee Gang Hyoung, Park Sun Ju, Yoon Ki Bok, Oh-Hashi Kentaro, Kim Sung Tae, Chae Sehyun, Cho Sung Kweon, Weon Byung Mook, Kim Jiyoon, Bin Bum-Ho
School of Advanced Materials Science & Engineering, Sungkyunkwan University, Suwon 16419, South Korea; Research Center for Advanced Materials Technology, Sungkyunkwan University, Suwon 16419, South Korea.
Department of Biological Sciences, Ajou University, Suwon 16499, South Korea.
Dev Cell. 2025 May 5;60(9):1304-1320.e7. doi: 10.1016/j.devcel.2024.12.024. Epub 2025 Jan 6.
Golgi abnormalities have been linked to aging and age-related diseases, yet the underlying causes and functional consequences remain poorly understood. This study identifies the interaction between age-associated zinc deficiency and Golgi stress as a critical factor in cellular aging. Senescent Golgi bodies from human fibroblasts show a fragmented Golgi structure, associated with a decreased interaction of the zinc-dependent Golgi-stacking protein complex Golgin45-GRASP55. Golgi stress is increased, and functions such as glycosylation and vesicle transport are impaired. These disturbances promote Golgi and perinuclear microtubule disassembly and subsequent mislocalization of intracellular proteins associated with cellular signaling and epigenetic control. Pharmacological induction of Golgi stress or zinc deficiency, or ablation of the Golgi-associated zinc transporter gene Zip13 in mouse fibroblasts, replicate the characteristics of cellular senescence, emphasizing the critical role of Golgi-zinc homeostasis. These findings highlight the importance of adequate zinc intake and suggest targeting Golgi dysfunction as a therapeutic strategy for alleviating age-related cellular decline.
高尔基体异常与衰老及年龄相关疾病有关，但其潜在原因和功能后果仍知之甚少。本研究确定了年龄相关的锌缺乏与高尔基体应激之间的相互作用是细胞衰老的关键因素。来自人类成纤维细胞的衰老高尔基体呈现出碎片化的高尔基体结构，这与锌依赖性高尔基体堆叠蛋白复合物Golgin45 - GRASP55的相互作用减少有关。高尔基体应激增加，糖基化和囊泡运输等功能受损。这些紊乱促进了高尔基体和核周微管的解体，以及随后与细胞信号传导和表观遗传控制相关的细胞内蛋白质的错误定位。在小鼠成纤维细胞中，药理学诱导高尔基体应激或锌缺乏，或敲除与高尔基体相关的锌转运基因Zip13，可重现细胞衰老的特征，强调了高尔基体 - 锌稳态的关键作用。这些发现突出了充足锌摄入的重要性，并建议将靶向高尔基体功能障碍作为缓解与年龄相关的细胞衰退的治疗策略。
