Why genes extending lifespan in model organisms have not been consistently associated with human longevity and what it means to translation research.
Why genes extending lifespan in model organisms have not been consistently associated with human longevity and what it means to translation research.
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DOI：
10.4161/15384101.2014.950151
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
de Magalhães JP
中科院分区：
文献类型：
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作者：
de Magalhães JP
Deelen et al.（2014）在人类分子遗传学报告了迄今为止最大的人类长寿全基因组关联研究。虽然令人印象深刻，但在这项最新研究和一般的遗传关联研究中，都明显缺乏已知可显著延长啮齿动物寿命的基因与人类寿命的关联。在这里，我讨论了几种可能的解释，如长寿相关研究的内在局限性和长寿的复杂遗传结构。然而，有一种假说认为，模型生物中与长寿相关的基因与人类长寿相关的基因之间缺乏相关性，至少部分是由于动物研究的内在局限性和偏见。特别是，大多数模式生物的研究都是在遗传多样性有限的菌株中进行的，因此不适用于人类群体。这具有重要的意义，并且与最近的其他结果一起证明了由于热量限制而导致的啮齿动物中的菌株特异性长寿效应，它质疑了我们将令人兴奋的发现从衰老遗传学转化为人类疗法的能力。
A recent paper by Deelen et al. (2014) in Human Molecular Genetics reports the largest genome-wide association study of human longevity to date. While impressive, there is a remarkable lack of association of genes known to considerably extend lifespan in rodents with human longevity, both in this latest study and in genetic association studies in general. Here, I discuss several possible explanations, such as intrinsic limitations in longevity association studies and the complex genetic architecture of longevity. Yet one hypothesis is that the lack of correlation between longevity-associated genes in model organisms and genes associated with human longevity is, at least partly, due to intrinsic limitations and biases in animal studies. In particular, most studies in model organisms are conducted in strains of limited genetic diversity which are then not applicable to human populations. This has important implications and, together with other recent results demonstrating strain-specific longevity effects in rodents due to caloric restriction, it questions our capacity to translate the exciting findings from the genetics of aging to human therapies.