Primate aging in the mammalian scheme: the puzzle of extreme variation in brain aging
Primate aging in the mammalian scheme: the puzzle of extreme variation in brain aging
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DOI：
10.1007/s11357-011-9355-9
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发表时间：
2012-10-01
期刊：
影响因子：
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通讯作者：
Austad, Steven N.
中科院分区：
文献类型：
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作者：
Finch, Caleb E.;Austad, Steven N.
在较晚的年龄，人类具有发展阿尔茨海默病（AD）的高风险，到90岁时可能高达50%。虽然原猴和猴子表现出更多的实质性变化，但被检查的类人猿大脑显示出轻微的神经退行性变化。与啮齿类动物相比，灵长类动物发育和繁殖缓慢，寿命长。新大陆灵长类中既有寿命最长的猴子，也有寿命最短的猴子，而原猴亚目则发育最快，寿命最短。在灵长类动物中，类人猿的大脑最大，发育最慢，寿命最长。所有灵长类动物都有一定程度的缓慢进行性、与年龄相关的神经退行性变化。然而，除了人类之外，还没有任何物种表现出接近临床级AD的定期严重神经元丢失或认知能力下降。几种灵长类动物积累了广泛的弥漫性淀粉样β蛋白（A β）沉积，但只有一种原猴-灰鼠狐猴-经常发展接近AD神经元缠结的tau蛋白病。与猴子相比，非人类类人猿的大脑衰老变化甚至更轻微，这是一个令人深感困惑的观察结果。大脑老化中这些主要物种差异的遗传基础仍然不清楚，但不涉及非人类灵长类动物和人类相同的A β编码序列。虽然黑猩猩值得更多的研究，但我们注意到更小，寿命更短的物种，如绒猴和小狐猴对衰老研究的价值。所有使用灵长类动物的衰老研究的持续关注是，相对于实验室啮齿动物，灵长类动物饲养处于相对原始的状态，并且需要更好的饲养来控制感染和肥胖，以进行脑衰老研究。
At later ages, humans have high risk of developing Alzheimer disease (AD) which may afflict up to 50% by 90 years. While prosimians and monkeys show more substantial changes, the great apes brains examined show mild neurodegenerative changes. Compared with rodents, primates develop and reproduce slowly and are long lived. The New World primates contain some of the shortest as well as some of the longest-lived monkey species, while the prosimians develop the most rapidly and are the shortest lived. Great apes have the largest brains, slowest development, and longest lives among the primates. All primates share some level of slowly progressive, age-related neurodegenerative changes. However, no species besides humans has yet shown regular drastic neuron loss or cognitive decline approaching clinical grade AD. Several primates accumulate extensive deposits of diffuse amyloid-beta protein (A beta) but only a prosimian-the gray mouse lemur-regularly develops a tauopathy approaching the neurofibrillary tangles of AD. Compared with monkeys, nonhuman great apes display even milder brain-aging changes, a deeply puzzling observation. The genetic basis for these major species differences in brain aging remains obscure but does not involve the A beta coding sequence which is identical in nonhuman primates and humans. While chimpanzees merit more study, we note the value of smaller, shorter-lived species such as marmosets and small lemurs for aging studies. A continuing concern for all aging studies employing primates is that relative to laboratory rodents, primate husbandry is in a relatively primitive state, and better husbandry to control infections and obesity is needed for brain aging research.