Martinez-Lopez Nuria, Athonvarangkul Diana, Singh Rajat
Department of Medicine and Department of Molecular Pharmacology, Albert Einstein College of Medicine, 10461, Bronx, NY, USA.
Adv Exp Med Biol. 2015;847:73-87. doi: 10.1007/978-1-4939-2404-2_3.
Autophagy is a critical quality control pathway that is conserved across diverse systems ranging from simple unicellular organisms like yeast to more complex systems, for instance mammals. Although, the fundamental role of autophagy is to maintain cellular quality control through lysosomal degradation of unwanted proteins and organelles, recent studies have mapped several new functions of this pathway that range from fuel utilization, cellular differentiation to protection against cell death. Given the importance of this pathway in maintaining cellular homeostasis, it has been considered that compromised autophagy could contribute to several of the commonly observed age-associated pathologies including neurodegeneration, reduction of muscle mass, cardiac malfunction, excessive lipid accumulation in tissues and glucose intolerance. The present chapter describes the two best-characterized autophagy pathways—macroautophagy and chaperone-mediated autophagy, and discusses how changes in these pathways associate with age-associated disorders. Understanding how to maintain “clean cells” by activation of autophagy could be an attractive strategy to maintain healthspan in aged individuals.
自噬是一种关键的质量控制途径,在从酵母等简单单细胞生物到更复杂的系统(如哺乳动物)等各种不同系统中都保守存在。尽管自噬的基本作用是通过对不需要的蛋白质和细胞器进行溶酶体降解来维持细胞质量控制,但最近的研究已经确定了该途径的几种新功能,范围从燃料利用、细胞分化到防止细胞死亡。鉴于该途径在维持细胞稳态中的重要性,人们认为自噬受损可能导致几种常见的与年龄相关的病理状况,包括神经退行性变、肌肉量减少、心脏功能障碍、组织中脂质过度积累和葡萄糖不耐受。本章描述了两种特征最明确的自噬途径——巨自噬和伴侣介导的自噬,并讨论了这些途径的变化如何与年龄相关疾病相关联。了解如何通过激活自噬来维持“清洁细胞”可能是维持老年个体健康寿命的一种有吸引力的策略。