衰老是一个渐进且不可逆的生理过程，会显着增加发生各种疾病的风险，包括神经退行性疾病、心血管疾病、代谢疾病、肌肉骨骼疾病和免疫系统疾病。线粒体是产生能量的细胞器，它们的正常功能对于整体细胞健康至关重要。随着时间的推移，线粒体功能下降，导致有害活性氧 (ROS) 和 DNA 的释放增加，从而导致氧化应激、炎症和细胞损伤，这些都是与各种年龄相关的病理相关的常见特征。线粒体自噬的损伤，即通过自噬选择性去除受损或功能失调的线粒体，与年龄相关疾病的发生和进展有关。衰老过程中调节线粒体自噬水平的分子机制在很大程度上仍不清楚。 AMBRA1 是一种本质上无序的支架蛋白，具有调节增殖和自噬核心机制活性的独特特性。虽然 AMBRA1 在胚胎发育和肿瘤转化过程中的作用已被广泛研究，但由于 AMBRA1 缺陷引起的胚胎致死，其在成体组织有丝分裂后细胞中的功能受到限制。最近，AMBRA1 在有丝分裂后细胞选择性调节线粒体自噬中的关键作用已经显现。在这里，我们总结并讨论了这些结果，旨在全面了解 AMBRA1 的线粒体作用，以及 AMBRA1 的缺陷活性如何与年龄相关退行性疾病（包括肌营养不良/肌肉减少症、帕金森病）中观察到的线粒体自噬改变在功能上相关。疾病、阿尔茨海默病和年龄相关性黄斑变性。

Aging is a gradual and irreversible physiological process that significantly increases the risks of developing a variety of pathologies, including neurodegenerative, cardiovascular, metabolic, musculoskeletal, and immune system diseases. Mitochondria are the energy-producing organelles, and their proper functioning is crucial for overall cellular health. Over time, mitochondrial function declines causing an increased release of harmful reactive oxygen species (ROS) and DNA, which leads to oxidative stress, inflammation and cellular damage, common features associated with various age-related pathologies. The impairment of mitophagy, the selective removal of damaged or dysfunctional mitochondria by autophagy, is relevant to the development and progression of age-related diseases. The molecular mechanisms that regulates mitophagy levels in aging remain largely uncharacterized. AMBRA1 is an intrinsically disordered scaffold protein with a unique property of regulating the activity of both proliferation and autophagy core machineries. While the role of AMBRA1 during embryonic development and neoplastic transformation has been extensively investigated, its functions in post-mitotic cells of adult tissues have been limited due to the embryonic lethality caused by AMBRA1 deficiency. Recently, a key role of AMBRA1 in selectively regulating mitophagy in post-mitotic cells has emerged. Here we summarize and discuss these results with the aim of providing a comprehensive view of the mitochondrial roles of AMBRA1, and how defective activity of AMBRA1 has been functionally linked to mitophagy alterations observed in age-related degenerative disorders, including muscular dystrophy/sarcopenia, Parkinson diseases, Alzheimer diseases and age-related macular degeneration.