Shetty Ritu A, Forster Michael J, Sumien Nathalie
Department of Pharmacology and Neuroscience and Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie, Fort Worth, TX, 76107, USA,
Age (Dordr). 2013 Oct;35(5):1821-34. doi: 10.1007/s11357-012-9484-9. Epub 2012 Nov 10.
Coenzyme Q10 (CoQ) is widely available as a dietary supplement and remains under consideration as a treatment for age-associated neurodegenerative conditions. However, no studies have determined if supplementation, initiated relatively late in life, could have beneficial effects on mild functional impairments associated with normal brain aging. Accordingly, the current study assessed the effect of CoQ intake in older mice for which cognitive and psychomotor impairments were already evident. Separate groups of young (3.5 months) and relatively old mice (17.5 months) were fed a control diet or a diet supplemented with low (0.72 mg/g) or high (2.81 mg/g) concentrations of CoQ for 15 weeks. After 6 weeks, the mice were given tests for spatial learning (Morris water maze), spontaneous locomotor activity, motor coordination, and startle reflex. Age-related impairments in cognitive and psychomotor functions were evident in the 17.5-month-old mice fed the control diet, and the low-CoQ diet failed to affect any aspect of the impaired performance. However, in the Morris water maze test, old mice on the high-CoQ diet swam to the safe platform with greater efficiency than the mice on the control diet. The old mice supplemented with the high-CoQ diet did not show improvement when spatial performance was measured using probe trials and failed to show improvement in other tests of behavioral performance. Protein oxidative damage was decreased in the mitochondria from the heart, liver, and skeletal muscle of the high-CoQ-supplemented mice and, to some extent, in the brain mitochondria. Contrasting with the deleterious effect of long-term CoQ supplementation initiated during young adulthood previously published, this study suggests that CoQ improves spatial learning and attenuates oxidative damage when administered in relatively high doses and delayed until early senescence, after age-related declines have occurred. Thus, in individuals with age-associated symptoms of cognitive decline, high-CoQ intake may be beneficial.
辅酶Q10（CoQ）作为一种膳食补充剂广泛可得，并且仍在作为年龄相关神经退行性疾病的一种治疗方法进行研究。然而，尚无研究确定在生命后期开始补充辅酶Q10是否会对与正常脑老化相关的轻度功能损害产生有益影响。因此，本研究评估了辅酶Q10摄入对认知和精神运动障碍已经明显的老年小鼠的影响。将年轻（3.5个月）和相对年老的小鼠（17.5个月）分为不同组，分别喂食对照饮食或添加低浓度（0.72毫克/克）或高浓度（2.81毫克/克）辅酶Q的饮食，持续15周。6周后，对小鼠进行空间学习测试（莫里斯水迷宫）、自发运动活动、运动协调性和惊吓反射测试。在喂食对照饮食的17.5个月大的小鼠中，与年龄相关的认知和精神运动功能损害明显，低辅酶Q饮食未能影响受损表现的任何方面。然而，在莫里斯水迷宫测试中，喂食高辅酶Q饮食的老年小鼠比喂食对照饮食的小鼠更有效地游向安全平台。当使用探针试验测量空间表现时，补充高辅酶Q饮食的老年小鼠没有表现出改善，并且在其他行为表现测试中也没有表现出改善。补充高辅酶Q的小鼠心脏、肝脏和骨骼肌线粒体中的蛋白质氧化损伤减少，并且在某种程度上，脑线粒体中的氧化损伤也减少。与先前发表的在成年早期开始长期补充辅酶Q的有害作用形成对比，本研究表明，当以相对高的剂量给药并延迟到早衰期（在与年龄相关的衰退发生之后）时，辅酶Q可改善空间学习并减轻氧化损伤。因此，对于有与年龄相关的认知衰退症状的个体，高辅酶Q摄入量可能有益。
