Bonnefoy Marc, Drai Jocelyne, Kostka Tomasz
Service de médecine gériatrique, Pavillon Michel Perret. CH. Lyon-Sud, 69495 Pierre-Bénite.
Presse Med. 2002 Jul 27;31(25):1174-84.
FREE RADICALS AND THE THEORY OF AGING: Severe oxidative stress progressively leads to cell dysfunction and ultimately cell death. Oxidative stress is defined as an imbalance between pro-oxidants and/or free radicals on the one hand, and anti-oxidizing systems on the other. The oxygen required for living may indirectly be responsible for negative effects; these deleterious effects are due to the production of free radicals, which are toxic for the cells (superoxide anions, hydroxyl radicals, peroxyl radicals, hydrogen peroxide, hydroperoxides and peroxinitrite anions). Free radical attacks are responsible for cell damage and the targeted cells are represented by the cell membranes, which are particularly rich in unsaturated fatty acids, sensitive to oxidation reactions; DNA is also the target of severe attacks by these reactive oxygen species (ROS).
These are represented by the enzymes and free radical captors. The latter are readily oxidizable composites. The free radical captor or neutralization systems of these ROS use a collection of mechanisms, vitamins (E and C), enzymes [superoxide dismutase (SOD), glutathion peroxidase (GPx) and others], and glutathion reductase (GSH), capable of neutralizing peroxinitrite. The efficacy of this system is dependent on the genome for the enzymatic defence systems, and on nutrition for the vitamins. Some strategies aimed at reducing oxidative stress-related alterations have been performed in animals. However, only a few can be used and are efficient in humans, such as avoidance of unfavourable environmental conditions (radiation, dietary carcinogens, smoking...) and antioxidant dietary supplementation.
Epidemiological data suggest that antioxidants may have a beneficial effect on many age-related diseases: atherosclerosis, cancer, some neurodegenerative and ocular diseases. However, the widespread use of supplements is hampered by several factors: the lack of prospective and controlled studies; insufficient knowledge on the pro-oxidant, oxidant and ant-oxidant properties of the various supplements; growing evidence that free radicals are not only by-products, but also play an important role in cell signal transduction, apoptosis and infection control.
Although current data indicate that antioxidants cannot prolong maximal life span, the beneficial impact of antioxidants on various age-related degenerative diseases may forecast an improvement in life span and enhance quality of life. The current lack of sufficient data does not permit the systematic recommendation of anti-oxidants. Nevertheless, antioxidant-rich diets with fruit and vegetables should be recommended.
自由基与衰老理论:严重的氧化应激会逐渐导致细胞功能障碍并最终导致细胞死亡。氧化应激被定义为一方面促氧化剂和/或自由基与另一方面抗氧化系统之间的失衡。生命所需的氧气可能间接导致负面影响;这些有害影响是由于自由基的产生,自由基对细胞有毒性(超氧阴离子、羟基自由基、过氧自由基、过氧化氢、氢过氧化物和过氧亚硝酸盐阴离子)。自由基攻击会导致细胞损伤,而目标细胞以细胞膜为代表,细胞膜富含不饱和脂肪酸,对氧化反应敏感;DNA也是这些活性氧(ROS)严重攻击的目标。
由酶和自由基捕获剂代表。后者是易于氧化的复合物。这些ROS的自由基捕获或中和系统使用一系列机制、维生素(E和C)、酶[超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)等]以及谷胱甘肽还原酶(GSH),能够中和过氧亚硝酸盐。该系统的功效取决于酶防御系统的基因组以及维生素的营养状况。一些旨在减少与氧化应激相关改变的策略已在动物身上实施。然而,只有少数几种可用于人类且有效,例如避免不利的环境条件(辐射、饮食致癌物、吸烟等)和抗氧化剂膳食补充。
流行病学数据表明抗氧化剂可能对许多与年龄相关的疾病有有益影响:动脉粥样硬化、癌症、一些神经退行性疾病和眼部疾病。然而,补充剂的广泛使用受到几个因素的阻碍:缺乏前瞻性和对照研究;对各种补充剂的促氧化、氧化和抗氧化特性了解不足;越来越多的证据表明自由基不仅是副产品,而且在细胞信号转导、细胞凋亡和感染控制中也起重要作用。
尽管目前的数据表明抗氧化剂不能延长最大寿命,但抗氧化剂对各种与年龄相关的退行性疾病的有益影响可能预示着寿命的改善和生活质量的提高。目前缺乏足够的数据不允许系统地推荐抗氧化剂。然而,应推荐富含水果和蔬菜的抗氧化剂饮食。