Cavallini Gabriella, Donati Alessio, Gori Zina, Bergamini Ettore
Centro di Ricerca Interdipartimentale di Biologia e Patologia dell'Invecchiamento, Università degli Studi di Pisa, Scuola Medica, Via Roma 55. 56126 Pisa, Italy.
Curr Aging Sci. 2008 Mar;1(1):4-9. doi: 10.2174/1874609810801010004.
Accumulation of oxidatively altered cell components may play a role in the age-related cell deterioration and associated diseases. Caloric restriction is the most robust anti-aging intervention that extends lifespan and retards the appearance of age-associated diseases. Autophagy is a highly conserved cell-repair process in which the cytoplasm, including excess or aberrant organelles, is sequestered into double-membrane vesicles and delivered to the degradative vacuoles. Autophagy has an essential role in adaptation to fasting and changing environmental conditions. Several pieces of evidence show that autophagy may be an essential part in the anti-aging mechanism of caloric restriction: 1. The function of autophagy declines with increasing age; 2. The temporal pattern of the decline parallels the changes in biomarkers of membrane aging and in amino acid and hormone signalling. 3. These age-dependent changes in autophagy are prevented by calorie restriction. 4. The prevention of the changes in autophagy and biomarkers of aging co-varies with the effects of calorie restriction on life-span. 5. A long-lasting inhibition of autophagy accelerates the process of aging. 6. A long-lasting stimulation of autophagy retards the process of aging in rats. 7. Stimulation of autophagy may rescue older cells from accumulation of altered mtDNA. 8. Stimulation of autophagy counteracts the age-related hypercholesterolemia in rodents. It is suggested that the pharmacological intensification of suppression of aging (P.I.S.A. treatment) by the stimulation of autophagy might prove to be a big step towards retardation of aging and prevention of age-associated diseases in humans.
氧化改变的细胞成分的积累可能在与年龄相关的细胞衰退及相关疾病中起作用。热量限制是最有效的抗衰老干预措施，可延长寿命并延缓与年龄相关疾病的出现。自噬是一种高度保守的细胞修复过程，其中细胞质，包括多余或异常的细胞器，被隔离到双膜囊泡中并输送到降解液泡。自噬在适应禁食和不断变化的环境条件中起着至关重要的作用。有几条证据表明，自噬可能是热量限制抗衰老机制的重要组成部分：1. 自噬功能随年龄增长而下降；2. 下降的时间模式与膜老化生物标志物以及氨基酸和激素信号传导的变化平行。3. 热量限制可防止自噬中这些与年龄相关的变化。4. 自噬和衰老生物标志物变化的预防与热量限制对寿命的影响共同变化。5. 长期抑制自噬会加速衰老过程。6. 长期刺激自噬可延缓大鼠的衰老过程。7. 刺激自噬可能使老化细胞免受改变的线粒体DNA积累的影响。8. 刺激自噬可抵消啮齿动物中与年龄相关的高胆固醇血症。有人提出，通过刺激自噬来进行抗衰老的药理强化（P.I.S.A. 治疗）可能被证明是朝着延缓人类衰老和预防与年龄相关疾病迈出的重要一步。
