Studies of aging in Ames dwarf mice: Effects of caloric restriction
Studies of aging in Ames dwarf mice: Effects of caloric restriction
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DOI：
10.1007/s11357-000-0002-0
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发表时间：
2000-01-01
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影响因子：
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通讯作者：
Bartke, A
中科院分区：
文献类型：
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作者：
Mattison, JA;Wright, C;Bartke, A
Ames侏儒小鼠体型矮小，生长激素(GH)、催乳素(PRL)和促甲状腺激素(TSH)缺乏，它们比正常兄弟姐妹活得更长(1-1.25岁)。检查这些动物对热量限制(CR)的反应是有意义的，因为矮小鼠可能自愿地受到热量限制。我们正在测试一种假设，即这种可能的自然卡路里限制将否定强加的CR对寿命的任何好处。雌雄Ames侏儒小鼠和它们的正常对应鼠已经自由喂养(AL)或30%CR饮食25-29个月。每天对动物进行监测，并每周称重。在12-15个月龄时，CR小鼠的体重明显低于喂饲AL的同龄人(正常雌性：-42%，正常雄性：-23%，矮小雌性：-18.8%，矮小雄性：-22.2%)。只有在矮小的雌性中，这种显著的差异才会随着年龄的增长而消失。在一岁时，对每日食物消耗量的比较显示，雌性侏儒鼠每克体重消耗的食物明显多于正常雌性，雄性也有类似的趋势。虽然减少了30%的食物摄入，但CR组小鼠每克体重摄入的食物与AL组小鼠相同。在总体运动活动方面，CR组小鼠明显比AL组小鼠更活跃。在抑制性回避学习任务中，18-21个月大的侏儒小鼠比年龄和饮食匹配的正常小鼠表现出显著更好的保持能力。对衰老矮小鼠和正常小鼠的组织病理学分析表明，肿瘤的发生率在两组小鼠之间没有差异，但肿瘤似乎比正常小鼠发展得更晚。经过2.25年的研究，27%的AL正常人，52%的CR正常人，74%的AL侏儒和87%的CR侏儒仍然活着。我们得出结论，虽然Ames侏儒有许多共同的特征，但它们不是CR模仿体。CR是否会延缓Ames侏儒小鼠的衰老并导致进一步的寿命延长仍有待确定。
Ames dwarf mice, which are small and deficient in growth homone (GH), prolactin (PRL), and thyroid stimulating hormone (TSH) live much longer (1-1.25 years) than their normal siblings. It was of interest to examine the response of these animals to caloric restriction (CR) because of the possibility that dwarf mice are voluntarily caloric restricted. We are testing the hypothesis that this possible natural caloric restriction will negate any benefits of an imposed CR on lifespan.Male and female Ames dwarf mice and their normal counterparts have been fed ad libitum (AL) or a 30% CR diet for 25-29 months. Animals were monitored daily and weighed weekly. At 12-15 months of age, CR mice weighed significantly less than their AL fed counterparts (normal females: -42%, normal males: -23%, dwarf females: -18.8%, and dwarf males: -22.2%). Only in dwarf females has this significant difference disappeared with age. At one year of age, a comparison of daily food consumption revealed that female dwarf mice consume significantly more food per gram body weight than normal females and a similar tendency is evident for males. Although they received 30% less food, CR mice ate the same amount as AL mice per gram body weight.On measures of total locomotor activity, CR mice were significantly more active than their AL-fed counterparts. On an inhibitory avoidance learning task, 18-21 month old dwarf mice exhibited significantly better retention than their age- and diet-matched normal counterparts. Histopathological analysis in aging dwarf versus normal mice suggested that the incidence of tumors does not differ between the two groups but tumors appear to develop later in dwarf than in normal mice.After 2.25 years on the study 27% of AL normals, 52% of CR normals, 74% of AL dwarfs, and 87% of CR dwarfs are still alive. We conclude that Ames dwarfs are not CR mimetics although they share many characteristics. It remains to be determined whether CR will delay aging and cause a further life extension in Ames dwarf mice.