Haidurov Alexander, Budanov Andrei V
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Pearse Street, Dublin 2, Ireland; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Pearse Street, Dublin 2, Ireland; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Mech Ageing Dev. 2020 Dec;192:111379. doi: 10.1016/j.mad.2020.111379. Epub 2020 Oct 3.
Sestrins are a family of stress-responsive antioxidant proteins responsible for regulation of cell viability and metabolism. The best known Sestrin targets are mTORC1 and mTORC2 kinases that control different cellular processes including growth, viability, autophagy, and mitochondrial metabolism. Inactivation of the single Sestrin gene in invertebrates has an adverse impact on their healthspan and longevity, whereas each of the three Sestrin genes in mammals and other vertebrate organisms has a different impact on maintenance of a particular tissue, affecting its stress tolerance, function and regenerative capability. As a result, Sestrins attenuate ageing and suppress development of many age-related diseases including myocardial infarction, muscle atrophy, diabetes, and immune dysfunction, but exacerbate development of chronic obstructive pulmonary disease. Moreover, Sestrins play opposite roles in carcinogenesis in different tissues. Stem cells support tissue remodelling that influences ageing, and Sestrins might suppress ageing and age-related pathologies through control of stem cell biology. In this review, we will discuss the potential link between Sestrins, stem cells, and ageing.
硒蛋白是一类应激反应性抗氧化蛋白家族，负责调节细胞活力和新陈代谢。最著名的硒蛋白作用靶点是mTORC1和mTORC2激酶，它们控制着包括生长、活力、自噬和线粒体代谢在内的不同细胞过程。无脊椎动物中单个硒蛋白基因的失活对其健康寿命和寿命有不利影响，而哺乳动物和其他脊椎动物中的三个硒蛋白基因中的每一个对特定组织的维持都有不同的影响，影响其应激耐受性、功能和再生能力。因此，硒蛋白可延缓衰老并抑制许多与年龄相关疾病的发展，包括心肌梗死、肌肉萎缩、糖尿病和免疫功能障碍，但会加剧慢性阻塞性肺疾病的发展。此外，硒蛋白在不同组织的致癌过程中发挥着相反的作用。干细胞支持影响衰老的组织重塑，而硒蛋白可能通过控制干细胞生物学来抑制衰老和与年龄相关的病理变化。在这篇综述中，我们将讨论硒蛋白、干细胞和衰老之间的潜在联系。
