自由基老化理论:应用

Denham Harman MD, PhD
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引用次数: 12

摘要

衰老是增加死亡风险的变化的积累。衰老变化可归因于发育、遗传缺陷、环境、疾病和先天衰老过程。在发达国家,28岁以后的老龄化变化的主要原因是内源性化学反应,这些化学反应总的来说,随着年龄的增长,疾病和死亡的机会呈指数级增加。这些反应构成了“先天衰老过程”。在生活条件接近最佳的发达国家,这一过程是98-99%的28岁仍活着的人群患病和死亡的主要风险因素。在这些国家,出生时的平均预期寿命(ALE-B)在76-79岁之间,比老龄化所规定的约85岁的极限少6-9岁。自由基老化理论(FRTA)假设老化变化是由自由基反应引起的。这一理论表明,至少在某些情况下,降低自由基反应的起始速率和/或链长的措施可能会降低产生老化变化的反应速率,而不会显著抑制那些涉及维持和功能的反应。许多研究都支持这种可能性。FRTA的应用取得了丰硕成果。例如,它是延长寿命努力的有用指南,并为衰老现象提供了合理的解释(例如,疾病与年龄的关联,以及对发病机制、性别差距、生命早期事件与晚发疾病之间的关联,以及端粒随着细胞分裂而缩短)。此外,根据动物和流行病学研究,我们有理由预计,在过去40年里,越来越多的人群使用抗氧化剂补充剂和摄入抗氧化能力高的食物,有助于延长美国人的功能性寿命,因为这大大促进了"自由基疾病"的减少、人口中老年人比例的增加和这一群体中慢性残疾的减少。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Free radical theory of ageing: Applications

Ageing is the accumulation of changes that increase the risk of death. Ageing changes can be attributed to development, genetic defects, the environment, disease, and the inborn ageing process. The major contributors of ageing changes after age 28 in the developed countries are endogenous chemical reactions, which, collectively, exponentially increase the chance of disease and death with advancing age. These reactions constitute the “inborn ageing process”. This process is the major risk factor for disease and death of the 98–99% of cohorts still alive at age 28 in the developed countries, where living conditions are near optimum. In these countries average life expectancies at birth (ALE-B) range from 76–79 years, 6–9 years less than the limit of about 85 years imposed by ageing. The Free Radical Theory of Ageing (FRTA) postulates that ageing changes are caused by free radical reactions. This theory suggests the possibility that measures to decrease the rate of initiation and /or the chain length of free radical reactions may, at least in some cases, decrease the rate of reactions which produce ageing changes without significantly depressing those involved in maintenance and function. Many studies support this possibility. Applications of the FRTA have been fruitful. For example, it is a useful guide to the efforts to increase the life span, and it provides plausible explanations for ageing phenomena, (for example, the association of disease with age as well as insight into pathogenesis, the gender gap, the association between events in early life and late onset disease, and the shortening of telomeres with cell division). Further, it is reasonable to expect on the basis of animal and epidemiological studies, that the increasing population-wide use of antioxidant supplements and ingestion of foods high in antioxidant capacity over the past 40 years have helped to increase the functional life span in the U.S.A. by contributing significantly to the decline in “free radical diseases”, to increases in the fraction of elderly in the population, and to the decline in chronic disability in this group.

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