Bergamini E, Cavallini G, Donati A, Gori Z
Centro di Ricerca di Biologia e Patologia dell'Invecchiamento, University of Pisa, Scuola Medica, via Roma 55, 56126 Pisa, Italy.
Int J Biochem Cell Biol. 2004 Dec;36(12):2392-404. doi: 10.1016/j.biocel.2004.05.007.
Macroautophagy is a degradation/recycling system ubiquitous in eukariotic cells, which generates nutrients during fasting under the control of amino acids and hormones, and contributes to the turnover and rejuvenation of cellular components (long-lived proteins, cytomembranes and organelles). Tight coupling between these two functions may be the weak point in cell housekeeping. Ageing denotes a post-maturational deterioration of tissues and organs with the passage of time, due to the progressive accumulation of the misfunctioning cell components because of oxidative damage and an age-dependent decline of turnover rate and housekeeping. Caloric restriction (CR) and lower insulin levels may slow down many age-dependent processes and extend lifespan. Recent evidence is reviewed showing that autophagy is involved in ageing and in the anti-ageing action of anti-ageing calorie restriction: function of autophagy declines during adulthood and is almost negligible at older age; CR prevents the age-dependent decline of autophagic proteolysis and improves the sensitivity of liver cells to stimulation of lysosomal degradation; protection of autophagic proteolysis from the age-related decline co-varies with the duration and level of anti-ageing food restriction like the effects of CR extending lifespan; the pharmacological stimulation of macroautophagy has anti-ageing effects. Besides the involvement in ageing, macroautophagy may have an essential role in the pathogenesis of many age-associated diseases. Higher protein turnover may not fully account for the anti-ageing effects of macroautophagy, and effects of macroautophagy on housekeeping of the cell organelles, antioxidant machinery of cell membranes and transmembrane cell signaling should also be considered.
巨自噬是真核细胞中普遍存在的一种降解/循环利用系统，在禁食期间，它在氨基酸和激素的控制下产生营养物质，并有助于细胞成分（长寿蛋白、细胞膜和细胞器）的更新和年轻化。这两种功能之间的紧密耦合可能是细胞内环境稳定的薄弱环节。衰老指的是随着时间的推移，组织和器官在成熟后出现的退化，这是由于氧化损伤导致功能失调的细胞成分逐渐积累，以及周转率和细胞内环境稳定随年龄增长而下降所致。热量限制（CR）和较低的胰岛素水平可能会减缓许多与年龄相关的过程并延长寿命。本文综述了最近的证据，表明自噬参与衰老以及抗衰老热量限制的抗衰老作用：自噬功能在成年期下降，在老年时几乎可以忽略不计；CR可防止自噬蛋白水解随年龄增长而下降，并提高肝细胞对溶酶体降解刺激的敏感性；保护自噬蛋白水解免受与年龄相关的下降，与抗衰老食物限制的持续时间和水平共同变化，就像CR延长寿命的效果一样；巨自噬的药理刺激具有抗衰老作用。除了参与衰老过程外，巨自噬可能在许多与年龄相关疾病的发病机制中起重要作用。较高的蛋白质周转率可能无法完全解释巨自噬的抗衰老作用，还应考虑巨自噬对细胞器内环境稳定、细胞膜抗氧化机制和跨膜细胞信号传导的影响。
