衰老驱动代谢相关脂肪性肝病的机制及靶向治疗策略研究进展

陈睿; 陆伦根

doi:10.12449/JCH250626

衰老驱动代谢相关脂肪性肝病的机制及靶向治疗策略研究进展

DOI: 10.12449/JCH250626

陈睿,
陆伦根^, ,

上海交通大学医学院附属第一人民医院消化科，上海 200080

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：陈睿负责设计论文框架，查阅文献，撰写文章；陆伦根负责文章审校。

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通信作者:
陆伦根， lungenlu1965@163.com （ORCID： 0000-0002-1533-4068）

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出版历程
- 收稿日期: 2024-10-02
- 录用日期: 2024-11-11
- 出版日期: 2025-06-25

Advances in the mechanism of aging-driven metabolic associated fatty liver disease and related targeted therapeutic strategies

Rui CHEN,
Lungen LU^{,
,}

Department of Gastroenterology，The First People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine，Shanghai 200080，China

More Information

Corresponding author: LU Lungen， lungenlu1965@163.com （ORCID： 0000-0002-1533-4068）

摘要

摘要: 代谢相关脂肪性肝病（MAFLD）是一种与代谢紊乱相关的肝脏疾病，其特征是肝细胞内脂肪过度沉积，与胰岛素抵抗和遗传易感性密切相关。衰老是MAFLD发展的一个重要因素，与MAFLD患者的死亡率呈正相关。MAFLD的病理生理机制涉及脂质代谢紊乱、胰岛素抵抗、炎症和氧化应激，而衰老通过进一步影响这些关键机制加剧MAFLD的病理过程。细胞衰老是机体衰老的重要因素，针对衰老细胞的治疗策略，如减少衰老细胞的数量或抑制其分泌的炎症因子，可能有助于减缓MAFLD的进展。此外，新型调节因子的筛选为MAFLD治疗新药物的开发提供了新的靶点。尽管已有多种抗衰老疗法进入临床试验阶段，但衰老对肝脏影响的机制复杂，需要进一步验证这些治疗的特异性和潜在肝损伤。将MAFLD的多系统代谢性功能障碍治疗转化为针对衰老的专门化治疗，可能为MAFLD药物研发提供新思路。
- 非酒精性脂肪性肝病 /
- 细胞衰老 /
- 衰老 /
- 脂代谢障碍 /
- 胰岛素抵抗 /
- 炎症
Abstract: Metabolic associated fatty liver disease （MAFLD） is a liver disease associated with metabolic disorders， and it is characterized by excessive fat deposition in hepatocytes and is closely associated with insulin resistance and genetic susceptibility. Aging is an important factor in the progression of MAFLD and is positively correlated with the mortality rate of patients with MAFLD. The pathophysiological mechanisms of MAFLD involve lipid metabolism disorders， insulin resistance， inflammation， and oxidative stress， and aging exacerbates the pathological process of MAFLD by further affecting these key mechanisms. Cell senescence is an important factor in organismal aging， and therapeutic strategies targeting senescent cells can reduce the number of senescent cells or inhibit the inflammatory factors secreted by such cells， thereby helping to slow down the progression of MAFLD. In addition， the screening of novel regulatory factors provides new targets for the development of new drugs for MAFLD treatment. Although several anti-aging therapies have entered clinical trials， further studies are needed to validate the specificity and potential liver damage of these therapies due to the complex mechanisms of aging on the liver. Transforming multisystem metabolic dysfunction therapies for MAFLD into specialized therapies for aging may provide new ideas for MAFLD drug development.
- Non-alcoholic Fatty Liver Disease /
- Cellular Senescence /
- Aging /
- Lipid Metabolism Disorders /
- Insulin Resistance /
- Inflammation

HTML全文

注： HFD，高脂饮食；FFA，游离脂肪酸；CD36，脂肪酸转位酶；DNL，脂质从头合成；FABP-1，脂肪酸结合蛋白1；PPARα，过氧化物酶体增殖物激活受体α；FACS，脂肪酸酰辅酶A合成酶；CPT-1，肉碱棕榈酰转移酶1；ROS，活性氧；TG，甘油三酯；VLDL，极低密度脂蛋白；apoB，载脂蛋白B；MTTP，微粒体三酰甘油转移蛋白；GH，生长激素。

图 1 衰老与肝脂肪代谢相关机制

Figure 1. Role of aging in liver fat metabolism

下载: 全尺寸图片幻灯片

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