Metabolic Research Centre & School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia.
Integr Comp Biol. 2010 Nov;50(5):808-17. doi: 10.1093/icb/icq007. Epub 2010 Mar 15.
More than 100 years ago, Max Rubner combined the fact that both metabolic rate and longevity of mammals varies with body size to calculate that "life energy potential" (lifetime energy turnover per kilogram) was relatively constant. This calculation linked longevity to aerobic metabolism which in turn led to the "rate-of-living" and ultimately the "oxidative stress" theories of aging. However, the link between metabolic rate and longevity is imperfect. Although unknown in Rubner's time, one aspect of body composition of mammals also varies with body size, namely the fatty acid composition of membranes. Fatty acids vary dramatically in their susceptibility to peroxidation and the products of lipid peroxidation are very powerful reactive molecules that damage other cellular molecules. The "membrane pacemaker" modification of the "oxidative stress" theory of aging proposes that fatty acid composition of membranes, via its influence on peroxidation of lipids, is an important determinant of lifespan (and a link between metabolism and longevity). The relationship between membrane fatty acid composition and longevity is discussed for (1) mammals of different body size, (2) birds of different body size, (3) mammals and birds that are exceptionally long-living for their size, (4) strains of mice that vary in longevity, (5) calorie-restriction extension of longevity in rodents, (6) differences in longevity between queen and worker honeybees, and (7) variation in longevity among humans. Most of these comparisons support an important role for membrane fatty acid composition in the determination of longevity. It is apparent that membrane composition is regulated for each species. Provided the diet is not deficient in polyunsaturated fat, it has minimal influence on a species' membrane fatty acid composition and likely also on it's maximum longevity. The exceptional longevity of Homo sapiens combined with the limited knowledge of the fatty acid composition of human tissues support the potential importance of mitochondrial membranes in determination of longevity.
100 多年前，马克斯·鲁伯纳 (Max Rubner) 将哺乳动物的代谢率和寿命随体型变化的事实结合起来，计算出“生命能量潜能”（每公斤寿命能量转换）相对恒定。这一计算将寿命与有氧代谢联系起来，进而导致了“生活率”和最终的“氧化应激”衰老理论。然而，代谢率和寿命之间的联系并不完美。虽然鲁伯纳 (Rubner) 时代还不知道，但哺乳动物的身体成分的一个方面也随体型而变化，即膜的脂肪酸组成。脂肪酸在易受过氧化作用方面差异很大，而脂质过氧化的产物是非常强大的反应性分子，会破坏其他细胞分子。衰老的“氧化应激”理论的“膜起搏器”修正版提出，膜的脂肪酸组成通过其对脂质过氧化的影响，是寿命的重要决定因素（也是代谢和寿命之间的联系）。讨论了膜脂肪酸组成与寿命之间的关系，包括：（1）不同体型的哺乳动物；（2）不同体型的鸟类；（3）体型特别大的长寿哺乳动物和鸟类；（4）寿命长短不同的老鼠品系；（5）限制热量对啮齿动物寿命的延长；（6）蜂王和工蜂之间寿命的差异；（7）人类之间寿命的差异。这些比较中的大多数都支持膜脂肪酸组成在决定寿命中的重要作用。显然，膜组成是针对每个物种进行调节的。只要饮食中不缺乏多不饱和脂肪，它对物种的膜脂肪酸组成及其最大寿命的影响就很小。智人的异常长寿，加上对人体组织脂肪酸组成的有限了解，支持了线粒体膜在决定寿命方面的潜在重要性。
