揭示线粒体sirtuins在衰老相关疾病中的作用：从机制见解到治疗策略。

IF 11.9 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Metabolism: clinical and experimental Pub Date : 2025-07-24 DOI:10.1016/j.metabol.2025.156356

Yanyan Cao , Yan Wang , Na Zhao , Ziyue Yuan , Lan Zhang , Peng Jin

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引用次数: 0

摘要

线粒体sirtuins，包括SIRT3、SIRT4和SIRT5，通过调节氧化磷酸化、能量代谢和氧化还原平衡，在维持线粒体稳态中起关键作用。这些酶的失调与衰老相关疾病如神经退行性疾病、代谢性疾病和心血管疾病的发病密切相关。SIRT3已被广泛研究，显示出对氧化应激和代谢失调的保护作用。相比之下，虽然SIRT4和SIRT5的特征较少，但它们对胰岛素敏感性、氮代谢和线粒体功能的调节至关重要。本文综述了线粒体sirtuins在调节细胞代谢、氧化还原平衡和线粒体稳态中的作用，重点介绍了它们在衰老相关疾病的发生和进展中的作用。此外，我们提供了针对线粒体sirtuins的小分子调节剂的概述，旨在恢复细胞功能，减缓衰老过程，并为治疗衰老相关疾病提供新的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Unraveling the roles of mitochondrial sirtuins in aging-related diseases: From mechanistic insights to therapeutic strategies

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Unraveling the roles of mitochondrial sirtuins in aging-related diseases: From mechanistic insights to therapeutic strategies

Mitochondrial sirtuins, including SIRT3, SIRT4, and SIRT5, play pivotal roles in maintaining mitochondrial homeostasis by regulating oxidative phosphorylation, energy metabolism, and redox balance. Dysregulation of these enzymes is closely associated with the pathogenesis of aging-related diseases such as neurodegenerative diseases, metabolic diseases, and cardiovascular diseases. SIRT3 has been the most extensively studied, demonstrating protective effects against oxidative stress and metabolic dysregulation. In contrast, while SIRT4 and SIRT5 are less characterized, they are critical for the regulation of insulin sensitivity, nitrogen metabolism, and mitochondrial function. This review focuses on the involvement of mitochondrial sirtuins in modulating cellular metabolism, redox balance, and mitochondrial homeostasis, highlighting their roles in the development and progression of aging-related diseases. Furthermore, we provide an overview of small-molecule modulators targeting mitochondrial sirtuins, which aim to restore cellular function, attenuate aging processes, and offer novel therapeutic strategies for treating aging-related diseases.

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来源期刊

Metabolism: clinical and experimental 医学-内分泌学与代谢

CiteScore

18.90

自引率

3.10%

发文量

310

审稿时长

16 days

期刊介绍： Metabolism upholds research excellence by disseminating high-quality original research, reviews, editorials, and commentaries covering all facets of human metabolism. Consideration for publication in Metabolism extends to studies in humans, animal, and cellular models, with a particular emphasis on work demonstrating strong translational potential. The journal addresses a range of topics, including: - Energy Expenditure and Obesity - Metabolic Syndrome, Prediabetes, and Diabetes - Nutrition, Exercise, and the Environment - Genetics and Genomics, Proteomics, and Metabolomics - Carbohydrate, Lipid, and Protein Metabolism - Endocrinology and Hypertension - Mineral and Bone Metabolism - Cardiovascular Diseases and Malignancies - Inflammation in metabolism and immunometabolism