Healthy animals with extreme longevity
Healthy animals with extreme longevity
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DOI：
10.1126/science.1089169
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发表时间：
2003-10-24
期刊：
影响因子：
56.9
通讯作者：
Kenyon, C
中科院分区：
文献类型：
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作者：
Arantes-Oliveira, N;Berman, JR;Kenyon, C
在线虫秀丽隐杆线虫中，抑制胰岛素/IGF-1（胰岛素样生长因子 1）信号传导的突变（例如 daf-2 胰岛素/IGF-1 受体突变）可以使动物的寿命延长一倍 (1)。去除生殖系前体细胞还可将寿命延长约 60%(2)。这种寿命的延长并不是不孕的结果；而是不育的结果。这似乎是由于内分泌信号改变所致 (1, 2)。去除 daf-2 突变体的种系或整个生殖系统可以进一步延长寿命：这些动物的寿命是正常动物的四倍 (2)。 daf-2 活性的大幅降低会导致幼年动物进入称为“dauer”的滞育静止状态。相比之下，部分功能丧失的daf-2突变体可以生长到成年并且寿命很长。我们发现，通过将弱daf-2突变体（例如daf-2（e1368））作为幼虫进行dal-2 RNA干扰（RNAi）来进一步降低daf-2活性，可以在不触发dauer形成的情况下产生更大的寿命延长（图1）。此外，当我们切除这些经过 RNAi 处理的动物的生殖系统时，它们的寿命是正常动物的六倍。野生型的平均寿命为 20 天，而这些动物的平均寿命为 124 天（图 1）。事实上，只有 15% 的动物在前 3 个月内死亡。我们对这些动物的“生活质量”特别感兴趣，这可以通过检查它们的活动水平来解决。长寿的 daf-2 突变体分为两类。 1 类突变体类似于正常动物，而 2 类突变体则不协调并采取类似 dauer 的姿势 (3)。一些 2 类突变，无论是单独的还是与其他寿命突变组合，都会导致非常长的平均寿命延长（高达 5.5 倍）；然而，所有这些菌株都已被极度淡化
In the nematode Caenorhabditis elegans, mutations that inhibit insulin/IGF-1 (insulinlike growth factor 1) signaling, such as daf-2 insulin/IGF-1 receptor mutations, can double the life-span of the animal (1). Removing the germ-line precursor cells also extends lifespan by approximately 60%(2). This lifespan extension is not a result of sterility; it appears to be due to altered endocrine signaling (1, 2). Removal of the germ line or the entire reproductive system of daf-2 mutants can further extend life-span: these animals can live four times as long as normal (2). Strong reduction of daf-2 activity causes juvenile animals to enter a quiescent state of diapause called dauer. In contrast, partial loss-of-functiondaf-2mu-tants grow to adulthood and have long life-spans. We found that reducing daf-2 activity further by subjecting weak daf-2 mutants, such as daf-2 (e1368), as young larvae to dal-2 RNA interference (RNAi) produced larger increases in life-span without triggering dauer formation (Fig. 1). Moreover, when we removed the reproductive systems of these RNAi-treated animals, they lived six times as long as normal. Whereas the mean life-span of wild type was 20 days, these animals had mean life-spans of 124 days (Fig. 1). In fact, only 15% of the animals died in the first 3 months.We were particularly interested in these animals’“quality of life,” which can be addressed by examining their level of activity. Long-lived daf-2 mutants fall into two classes. Class 1 mutants resemble normal animals, whereas class 2 mutants are uncoordinated and adopt a dauerlike posture (3). Some class 2 mutations, either singly or in combination with other life-span mutations, cause very long mean life-span extensions (up to 5.5-fold); however, all of these strains have been extremely le-