Hagen T M, Ingersoll R T, Lykkesfeldt J, Liu J, Wehr C M, Vinarsky V, Bartholomew J C, Ames A B
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA.
FASEB J. 1999 Feb;13(2):411-8. doi: 10.1096/fasebj.13.2.411.
A diet supplemented with (R)-lipoic acid, a mitochondrial coenzyme, was fed to old rats to determine its efficacy in reversing the decline in metabolism seen with age. Young (3 to 5 months) and old (24 to 26 months) rats were fed an AIN-93M diet with or without (R)-lipoic acid (0.5% w/w) for 2 wk, killed, and their liver parenchymal cells were isolated. Hepatocytes from untreated old rats vs. young controls had significantly lower oxygen consumption (P<0. 03) and mitochondrial membrane potential. (R)-Lipoic acid supplementation reversed the age-related decline in O2 consumption and increased (P<0.03) mitochondrial membrane potential. Ambulatory activity, a measure of general metabolic activity, was almost threefold lower in untreated old rats vs. controls, but this decline was reversed (P<0.005) in old rats fed (R)-lipoic acid. The increase of oxidants with age, as measured by the fluorescence produced on oxidizing 2',7'-dichlorofluorescin, was significantly lowered in (R)-lipoic acid supplemented old rats (P<0.01). Malondialdehyde (MDA) levels, an indicator of lipid peroxidation, were increased fivefold with age in cells from unsupplemented rats. Feeding rats the (R)-lipoic acid diet reduced MDA levels markedly (P<0.01). Both glutathione and ascorbic acid levels declined in hepatocytes with age, but their loss was completely reversed with (R)-lipoic acid supplementation. Thus, (R)-lipoic acid supplementation improves indices of metabolic activity as well as lowers oxidative stress and damage evident in aging.
给老年大鼠喂食添加了线粒体辅酶（R）-硫辛酸的饮食，以确定其在逆转随年龄增长而出现的新陈代谢下降方面的功效。将年轻（3至5个月）和老年（24至26个月）大鼠喂食含或不含（R）-硫辛酸（0.5% w/w）的AIN-93M饮食2周，然后处死，并分离其肝脏实质细胞。未经处理的老年大鼠与年轻对照大鼠的肝细胞相比，氧消耗量显著降低（P<0.03），线粒体膜电位也较低。补充（R）-硫辛酸可逆转与年龄相关的氧消耗量下降，并增加（P<0.03）线粒体膜电位。衡量一般代谢活动的自主活动在未经处理的老年大鼠中比对照大鼠低近三倍，但在喂食（R）-硫辛酸的老年大鼠中这种下降得到了逆转（P<0.005）。通过氧化2',7'-二氯荧光素产生的荧光测量，随年龄增长的氧化剂增加在补充（R）-硫辛酸的老年大鼠中显著降低（P<0.01）。丙二醛（MDA）水平是脂质过氧化的指标，在未补充大鼠的细胞中随年龄增长增加了五倍。给大鼠喂食（R）-硫辛酸饮食可显著降低MDA水平（P<0.01）。随着年龄增长，肝细胞中的谷胱甘肽和抗坏血酸水平均下降，但补充（R）-硫辛酸可完全逆转其损失。因此，补充（R）-硫辛酸可改善代谢活动指标，并降低衰老过程中明显的氧化应激和损伤。
