Harman D
Proc Natl Acad Sci U S A. 1981 Nov;78(11):7124-8. doi: 10.1073/pnas.78.11.7124.
Aging is the progressive accumulation of changes with time that are associated with or responsible for the ever-increasing susceptibility to disease and death which accompanies advancing age. These time-related changes are attributed to the aging process. The nature of the aging process has been the subject of considerable speculation. Accumulating evidence now indicates that the sum of the deleterious free radical reactions going on continuously throughout the cells and tissues constitutes the aging process or is a major contributor to it. In mammalian systems the free radical reactions are largely those involving oxygen. Dietary manipulations expected to lower the rate of production of free radical reaction damage have been shown (i) to increase the life span of mice, rats, fruit flies, nematodes, and rotifers, as well as the "life span" of neurospora; (ii) to inhibit development of some forms of cancer; (iii) to enhance humoral and cell-mediated immune responses; and (iv) to slow development of amyloidosis and the autoimmune disorders of NZB and NZB/NZW mice. In addition, studies strongly suggest that free radical reactions play a significant role in the deterioration of the cardiovascular and central nervous systems with age. The free radical theory of aging provides reasonable explanations for age-associated phenomena, including (i) the relationship of the average life spans of mammalian species to their basal metabolic rates, (ii) the clustering of degenerative diseases in the terminal part of the life span, (iii) the beneficial effect of food restriction on life span, (iv) the greater longevity of females, and (v) the increase in autoimmune manifestations with age. It is not unreasonable to expect on the basis of present data that the healthy life span can be increased by 5-10 or more years by keeping body weight down, at a level compatible with a sense of well-being, while ingesting diets adequate in essential nutrients but designed to minimize random free radical reactions in the body.
衰老指的是随着时间推移，与年龄增长相伴的对疾病和死亡易感性不断增加相关或有责任的变化的渐进性积累。这些与时间相关的变化归因于衰老过程。衰老过程的本质一直是大量猜测的主题。现在越来越多的证据表明，在细胞和组织中持续进行的有害自由基反应的总和构成了衰老过程或对其有主要贡献。在哺乳动物系统中，自由基反应主要是那些涉及氧气的反应。已表明，预期能降低自由基反应损伤产生速率的饮食调控（i）可延长小鼠、大鼠、果蝇、线虫和轮虫的寿命，以及脉孢菌的“寿命”；（ii）抑制某些形式癌症的发展；（iii）增强体液免疫和细胞介导的免疫反应；（iv）减缓淀粉样变性以及NZB和NZB/NZW小鼠自身免疫性疾病的发展。此外，研究有力地表明，自由基反应在心血管和中枢神经系统随年龄的退化中起重要作用。衰老的自由基理论为与年龄相关的现象提供了合理的解释，包括（i）哺乳动物物种的平均寿命与其基础代谢率的关系；（ii）退行性疾病在寿命末期的聚集；（iii）食物限制对寿命的有益影响；（iv）女性的更长寿命；以及（v）自身免疫表现随年龄的增加。基于目前的数据，通过将体重保持在与幸福感相符的水平，同时摄入富含必需营养素但旨在尽量减少体内随机自由基反应的饮食，有望将健康寿命延长5至10年或更长时间，这并非不合理。
