Mitochondria in cell senescence: A Friend or Foe?

3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Qian Chen, Lindon Young, Robert Barsotti
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引用次数: 1

Abstract

Cell senescence denotes cell growth arrest in response to continuous replication or stresses damaging DNA or mitochondria. Mounting research suggests that cell senescence attributes to aging-associated failing organ function and diseases. Conversely, it participates in embryonic tissue maturation, wound healing, tissue regeneration, and tumor suppression. The acute or chronic properties and microenvironment may explain the double faces of senescence. Senescent cells display unique characteristics. In particular, its mitochondria become elongated with altered metabolomes and dynamics. Accordingly, mitochondria reform their function to produce more reactive oxygen species at the cost of low ATP production. Meanwhile, destructed mitochondrial unfolded protein responses further break the delicate proteostasis fostering mitochondrial dysfunction. Additionally, the release of mitochondrial damage-associated molecular patterns, mitochondrial Ca2+ overload, and altered NAD+ level intertwine other cellular organelle strengthening senescence. These findings further intrigue researchers to develop anti-senescence interventions. Applying mitochondrial-targeted antioxidants reduces cell senescence and mitigates aging by restoring mitochondrial function and attenuating oxidative stress. Metformin and caloric restriction also manifest senescent rescuing effects by increasing mitochondria efficiency and alleviating oxidative damage. On the other hand, Bcl2 family protein inhibitors eradicate senescent cells by inducing apoptosis to facilitate cancer chemotherapy. This review describes the different aspects of mitochondrial changes in senescence and highlights the recent progress of some anti-senescence strategies.

线粒体在细胞衰老中的作用:是敌是友?
细胞衰老是指细胞因持续复制或应激损伤DNA或线粒体而导致细胞生长停滞。越来越多的研究表明,细胞衰老归因于与衰老相关的器官功能衰竭和疾病。相反,它参与胚胎组织成熟、伤口愈合、组织再生和肿瘤抑制。衰老的急性或慢性特性和微环境可以解释衰老的两面性。衰老细胞表现出独特的特征。特别是,它的线粒体随着代谢组和动力学的改变而变长。因此,线粒体改变其功能,以降低ATP的产生为代价产生更多的活性氧。同时,被破坏的线粒体未折叠蛋白反应进一步打破了微妙的蛋白质平衡,从而导致线粒体功能障碍。此外,线粒体损伤相关分子模式的释放、线粒体Ca2+超载和NAD+水平的改变与其他细胞器相互交织,加强衰老。这些发现进一步激发了研究人员开发抗衰老干预措施的兴趣。应用线粒体靶向抗氧化剂通过恢复线粒体功能和减轻氧化应激来减少细胞衰老和减缓衰老。二甲双胍和热量限制也通过提高线粒体效率和减轻氧化损伤而表现出延缓衰老的作用。另一方面,Bcl2家族蛋白抑制剂通过诱导细胞凋亡来消除衰老细胞,促进癌症化疗。本文综述了衰老过程中线粒体变化的不同方面,并重点介绍了一些抗衰老策略的最新进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Advances in protein chemistry and structural biology
Advances in protein chemistry and structural biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
7.40
自引率
0.00%
发文量
66
审稿时长
>12 weeks
期刊介绍: Published continuously since 1944, The Advances in Protein Chemistry and Structural Biology series has been the essential resource for protein chemists. Each volume brings forth new information about protocols and analysis of proteins. Each thematically organized volume is guest edited by leading experts in a broad range of protein-related topics.
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