Long live FOXO: unraveling the role of FOXO proteins in aging and longevity.
Long live FOXO: unraveling the role of FOXO proteins in aging and longevity.
复制标题
万能福克斯：揭开Foxo蛋白在衰老和寿命中的作用。
DOI：
10.1111/acel.12427
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发表时间：
2016-04
期刊：
影响因子：
7.8
通讯作者：
Link W
中科院分区：
文献类型：
--
作者：
Martins R;Lithgow GJ;Link W
衰老是癌症、心血管疾病和神经退行性疾病等与年龄相关的疾病的关键危险因素。人类长寿和健康老龄化是受环境和遗传因素影响的复杂表型。遗传对寿命的贡献随着年龄的增长而急剧增加，这一事实为长寿个体携带“保护基因”的研究提供了基础。研究一致表明 FOXO（叉头盒 O）转录因子是衰老和长寿的重要决定因素。 FOXO 蛋白代表从秀丽隐杆线虫到哺乳动物中保守的转录因子亚家族，充当胰岛素和胰岛素样生长因子信号传导下游寿命的关键调节因子。无脊椎动物基因组有一个 FOXO 基因，而哺乳动物有 4 个 FOXO 基因：FOXO1、FOXO3、FOXO4 和 FOXO6。在哺乳动物中，该亚家族参与调节应激抵抗、新陈代谢、细胞周期停滞和细胞凋亡的广泛关键细胞过程。它们在决定寿命方面的作用很复杂，有待充分阐明。在这篇综述中，我们将在从水螅到哺乳动物的不同动物模型中讨论 FOXO 因子促进长寿的机制。此外，还将讨论 FOXO 作为人类极端长寿和健康寿命贡献者的令人信服的证据。
Aging constitutes the key risk factor for age‐related diseases such as cancer and cardiovascular and neurodegenerative disorders. Human longevity and healthy aging are complex phenotypes influenced by both environmental and genetic factors. The fact that genetic contribution to lifespan strongly increases with greater age provides basis for research on which “protective genes” are carried by long‐lived individuals. Studies have consistently revealed FOXO (Forkhead box O) transcription factors as important determinants in aging and longevity. FOXO proteins represent a subfamily of transcription factors conserved from Caenorhabditis elegans to mammals that act as key regulators of longevity downstream of insulin and insulin‐like growth factor signaling. Invertebrate genomes have one FOXO gene, while mammals have four FOXO genes: FOXO1, FOXO3, FOXO4, and FOXO6. In mammals, this subfamily is involved in a wide range of crucial cellular processes regulating stress resistance, metabolism, cell cycle arrest, and apoptosis. Their role in longevity determination is complex and remains to be fully elucidated. Throughout this review, the mechanisms by which FOXO factors contribute to longevity will be discussed in diverse animal models, from Hydra to mammals. Moreover, compelling evidence of FOXOs as contributors for extreme longevity and health span in humans will be addressed.