Arking Robert, Buck Steven, Hwangbo Dae-Sung, Lane Mark
Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202, USA.
Ann N Y Acad Sci. 2002 Apr;959:251-62; discussion 463-5. doi: 10.1111/j.1749-6632.2002.tb02097.x.
Evolutionary theories suggest that the expression of extended longevity depends on the organism's ability to shift energy from reproduction to somatic maintenance. New data led us to reexamine our older data and integrate the two into a larger picture of the genetic and metabolic alterations required if the animal is to live long. Our Ra normal-lived control strain can express any one of three different extended longevity phenotypes, only one of which involves significant and proportional increases in both mean and maximum longevity and thus a delayed onset of senescence. This phenotype is dependent on the up-regulation of the antioxidant defense system (ADS) genes and enzymes. Animals that express this phenotype typically have a pattern of altered specific activities in metabolically important enzymes, suggesting they are necessary to support the NAD+/NADP+ reducing system required for the continued high ADS enzyme activities. Fecundity data suggests that the energy required for this higher level of somatic maintenance initially came from a reduced egg production. This was only transient, however, for the females significantly increased their fecundity in later generations while still maintaining their longevity. The energy required for this enhanced fecundity was probably obtained from an increased metabolic efficiency, for the mitochondria of the La long-lived strain are metabolically more efficient and have a lower leakage of reactive oxygen species (ROS) to the cytosol. Selection pressures that do not lead to these shifts in energy allocations result in extended longevity phenotypes characterized by increased early survival or increased late survival but not by a delayed onset of senescence.
进化理论表明，延长寿命的表达取决于生物体将能量从繁殖转移到体细胞维持的能力。新的数据促使我们重新审视我们以前的数据，并将两者整合到一个更大的图景中，即如果动物要长寿，所需的遗传和代谢改变。我们的Ra正常寿命对照品系可以表达三种不同的延长寿命表型中的任何一种，其中只有一种涉及平均寿命和最大寿命的显著且成比例的增加，从而延缓衰老的发生。这种表型依赖于抗氧化防御系统（ADS）基因和酶的上调。表达这种表型的动物通常在代谢重要酶中具有特定活性改变的模式，这表明它们对于支持持续高ADS酶活性所需的NAD+/NADP+还原系统是必要的。繁殖力数据表明，这种更高水平的体细胞维持所需的能量最初来自于产卵量的减少。然而，这只是暂时的，因为雌性在后代中显著提高了它们的繁殖力，同时仍然保持它们的寿命。这种增强的繁殖力所需的能量可能是从提高的代谢效率中获得的，因为La长寿品系的线粒体在代谢上更有效率，并且向细胞质中泄漏的活性氧（ROS）更少。不会导致这些能量分配变化的选择压力会导致延长寿命的表型，其特征是早期存活率增加或晚期存活率增加，但不是衰老延迟。
