Aging is associated with multiple human pathologies. In the past few years mitochondrial homeostasis has been well correlated with age-related disorders and longevity. Mitochondrial homeostasis involves generation, biogenesis and removal of dysfunctional mitochondria via mitophagy. Mitophagy is regulated by various mitochondrial and extra-mitochondrial factors including morphology, oxidative stress and DNA damage. For decades, DNA damage and inefficient DNA repair have been considered as major determinants for age-related disorders. Although defects in DNA damage recognition and repair and mitophagy are well documented to be major factors in age-associated diseases, interactivity between these is poorly understood. Mitophagy efficiency decreases with age leading to accumulation of dysfunctional mitochondria enhancing the severity of age-related disorders including neurodegenerative diseases, inflammatory diseases, cancer, diabetes and many more. Therefore, mitophagy is being targeted for intervention in age-associated disorders. NAD+ supplementation has emerged as one intervention to target both defective DNA repair and mitophagy. In this review, we discuss the molecular signaling pathways involved in regulation of DNA damage and repair and of mitophagy, and we highlight the opportunities for clinical interventions targeting these processes to improve the quality of life during aging.

中文翻译：

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人类衰老过程中的线粒体自噬和 DNA 损伤信号传导。


衰老与多种人类病理有关。在过去的几年中，线粒体稳态与年龄相关疾病和长寿密切相关。线粒体稳态涉及通过线粒体自噬产生、生物发生和去除功能失调的线粒体。线粒体自噬受到多种线粒体和线粒体外因素的调节，包括形态、氧化应激和 DNA 损伤。几十年来，DNA 损伤和低效 DNA 修复一直被认为是与年龄相关的疾病的主要决定因素。尽管 DNA 损伤识别和修复以及线粒体自噬的缺陷已被充分证明是与年龄相关的疾病的主要因素，但人们对它们之间的相互作用知之甚少。线粒体自噬效率随着年龄的增长而降低，导致功能失调的线粒体积累，从而加剧与年龄相关的疾病的严重程度，包括神经退行性疾病、炎症性疾病、癌症、糖尿病等。因此，线粒体自噬正在成为干预年龄相关疾病的目标。 NAD+ 补充剂已成为针对缺陷 DNA 修复和线粒体自噬的一种干预措施。在这篇综述中，我们讨论了参与 DNA 损伤和修复以及线粒体自噬调节的分子信号传导途径，并强调了针对这些过程进行临床干预以改善衰老过程中生活质量的机会。