Orentreich N, Matias J R, DeFelice A, Zimmerman J A
Orentreich Foundation for the Advancement of Science, Inc., Biomedical Research Station, Cold Spring-on-Hudson, NY 10516.
J Nutr. 1993 Feb;123(2):269-74. doi: 10.1093/jn/123.2.269.
Dietary energy restriction has been a widely used means of experimentally extending mammalian life span. We report here that lifelong reduction in the concentration of a single dietary component, the essential amino acid L-methionine, from 0.86 to 0.17% of the diet results in a 30% longer life span of male Fischer 344 rats. Methionine restriction completely abolished growth, although food intake was actually greater on a body weight basis. Studies of energy consumption in early life indicated that the energy intake of 0.17% methionine-fed animals was near normal for animals of their size, although consumption per animal was below that of the much larger 0.86% methionine-fed rats. Increasing the energy intake of rats fed 0.17% methionine failed to increase their rate of growth, whereas restricting 0.85% methionine-fed rats to the food intake of 0.17% methionine-fed animals did not materially reduce growth, indicating that food restriction was not a factor in life span extension in these experiments. The biochemically well-defined pathways of methionine metabolism and utilization offer the potential for uncovering the precise mechanism(s) underlying this specific dietary restriction-related extension of life span.
饮食能量限制一直是实验中延长哺乳动物寿命的一种广泛使用的方法。我们在此报告,将单一饮食成分——必需氨基酸L-蛋氨酸的浓度从饮食的0.86%终身降低至0.17%,可使雄性Fischer 344大鼠的寿命延长30%。蛋氨酸限制完全抑制了生长,尽管按体重计算食物摄入量实际上更高。对早期生命阶段能量消耗的研究表明,摄入0.17%蛋氨酸的动物的能量摄入量对于其体型的动物来说接近正常,尽管每只动物的消耗量低于体型大得多的摄入0.86%蛋氨酸的大鼠。增加摄入0.17%蛋氨酸的大鼠的能量摄入量未能提高其生长速度,而将摄入0.85%蛋氨酸的大鼠的食物摄入量限制为摄入0.17%蛋氨酸的动物的摄入量,并不会实质性地降低生长速度,这表明在这些实验中食物限制不是寿命延长的一个因素。蛋氨酸代谢和利用的生物化学定义明确的途径为揭示这种与特定饮食限制相关的寿命延长背后的精确机制提供了可能性。