Hagen T M, Ingersoll R T, Wehr C M, Lykkesfeldt J, Vinarsky V, Bartholomew J C, Song M H, Ames B N
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9562-6. doi: 10.1073/pnas.95.16.9562.
Mitochondrial function and ambulatory activity were monitored after feeding old rats acetyl-L-carnitine (ALCAR). Young (3-5 mo) and old (22-28 mo) rats were given a 1.5% (wt/vol) solution of ALCAR in their drinking water for 1 mo, were sacrificed, and their liver parenchymal cells were isolated. ALCAR supplementation significantly reverses the age-associated decline of mitochondrial membrane potential, as assessed by rhodamine 123 staining. Cardiolipin, which declines significantly with age, is also restored. ALCAR increases cellular oxygen consumption, which declines with age, to the level of young rats. However, the oxidant production per oxygen consumed, as measured by 2',7'-dichlorofluorescin fluorescence levels, is approximately 30% higher than in untreated old rats. Cellular glutathione and ascorbate levels were nearly 30% and 50% lower, respectively, in cells from ALCAR-supplemented old rats than in untreated old rats, further indicating that ALCAR supplementation might increase oxidative stress. Ambulatory activity in young and old rats was quantified as a general measure of metabolic activity. Ambulatory activity, defined as mean total distance traveled, in old rats is almost 3-fold lower than in young animals. ALCAR supplementation increases ambulatory activity significantly in both young and old rats, with the increase being larger in old rats. Thus, ALCAR supplementation to old rats markedly reverses the age-associated decline in many indices of mitochondrial function and general metabolic activity, but may increase oxidative stress.
给老龄大鼠喂食乙酰-L-肉碱（ALCAR）后，对其线粒体功能和活动能力进行了监测。将年轻（3 - 5个月）和老龄（22 - 28个月）大鼠的饮用水中加入1.5%（重量/体积）的ALCAR溶液，持续1个月，然后处死大鼠并分离其肝实质细胞。通过罗丹明123染色评估，补充ALCAR可显著逆转与年龄相关的线粒体膜电位下降。随着年龄显著下降的心磷脂也得到恢复。ALCAR可使随年龄下降的细胞氧消耗增加至年轻大鼠的水平。然而，通过2',7'-二氯荧光素荧光水平测量，每消耗一分子氧产生的氧化剂比未处理的老龄大鼠高出约30%。补充ALCAR的老龄大鼠细胞中的谷胱甘肽和抗坏血酸水平分别比未处理的老龄大鼠低近30%和50%，这进一步表明补充ALCAR可能会增加氧化应激。将年轻和老龄大鼠的活动能力作为代谢活动的一项总体指标进行量化。活动能力定义为平均总行进距离，老龄大鼠的活动能力比年轻动物低近3倍。补充ALCAR可显著增加年轻和老龄大鼠的活动能力，老龄大鼠的增加幅度更大。因此，给老龄大鼠补充ALCAR可显著逆转与年龄相关的线粒体功能和总体代谢活动多项指标的下降，但可能会增加氧化应激。
