The role of autophagy in aging - Its essential part in the anti-aging mechanism of caloric restriction
The role of autophagy in aging - Its essential part in the anti-aging mechanism of caloric restriction
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DOI：
10.1196/annals.1396.020
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Gori, Zina
中科院分区：
文献类型：
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作者：
Bergamini, Ettore;Cavallini, Gabriella;Gori, Zina
衰老是指随着时间的推移，细胞和生物体的成熟后退化，对挑战的脆弱性和与年龄有关的疾病的患病率增加，以及生存能力下降。这种恶化的原因可能是活性氧（ROS）的产生增加、氧化损伤和不完整的“内务管理”。热量限制是迄今为止已知的最有效的抗衰老干预措施。通过给动物喂食减少40%的饮食或每隔一天随意喂食，对中位寿命和最长寿命也有类似的有益影响。在这两种情况下，动物都被迫在禁食和激活自噬的状态下度过大部分时间。在真核生物中，自噬是一个高度保守的过程，在这个过程中，细胞质，包括过量或异常的细胞器，被隔离到双膜囊泡中，并被运送到溶酶体/液泡中，进行分解并最终回收产生的大分子。这一过程在适应禁食和不断变化的环境条件、发育过程中的细胞重塑以及衰老细胞中ros超生成细胞器的积累中起着重要作用。一些证据表明，自噬参与衰老，是热量限制抗衰老机制的重要组成部分。作为一项应用，通过使用抗脂溶药物来增强自噬，可以在不到6小时内将衰老细胞从改变mtDNA的积累中拯救出来。结论：自噬强化（PISA治疗）具有抗衰老作用，可能是人类延缓衰老和预防衰老相关疾病的重要一步。
Aging denotes a postmaturationl deterioration of cells and organisms with the passage of time, an increased vulnerability to challenges and prevalence of age-associated diseases, and a decreased ability to survive. Causes of this deterioration may be found in an enhanced production of reactive oxygen species (ROS) and oxidative damage and incomplete "housekeeping." Caloric restriction is the most robust anti-aging intervention known so far. Similar beneficial effects on median and maximum life span were obtained by feeding animals a 40%-reduced diet or by every-other-day ad libitum feeding. In both instances, animals are forced to spend a great part of their time in a state of fasting and activated autophagy. Autophagy is a highly conserved process in eukaryotes, in which the cytoplasm, including excess or aberrant organelles, is sequestered into double-membrane vesicles and delivered to the lysosome/vacuole, for breakdown and eventual recycling of the resulting macromolecules. This process has an essential role in adaptation to fasting and changing environmental conditions, cellular remodeling during development, and accumulation of altered ROS-hypergenerating organelles in older cells. Several pieces of evidence show that autophagy is involved in aging and is an essential part of the anti-aging mechanism of caloric restriction. As an application, intensification of autophagy by the administration of an antilipolytic drug rescued older cells from accumulation of altered mtDNA in less than 6 hours. It is concluded that the pharmacologic intensification of autophagy (PISA treatment) has anti-aging effects and might prove to be a big step toward retardation of aging and prevention of age-associated diseases in humans.