The genetics of caloric restriction in Caenorhabditis elegans
The genetics of caloric restriction in Caenorhabditis elegans
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DOI：
10.1073/pnas.95.22.13091
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发表时间：
1998-10-27
影响因子：
11.1
通讯作者：
Hekimi, S
中科院分区：
文献类型：
--
作者：
Lakowski, B;Hekimi, S
低热量摄入（热量限制）可以延长许多动物甚至人类的寿命，为了更好地了解热量限制如何延长寿命，我们使用遗传学方法和标准来研究其在线虫线虫中的作用机制。许多基因（eat基因）的突变通过破坏咽部（摄食器官）的功能而导致蠕虫部分饥饿。我们发现，大多数吃突变显着延长寿命（高达50%）。在秀丽隐杆线虫中，已经发现了许多可以延长寿命的其他基因的突变。已知两种遗传学上不同的延长寿命的机制：一种涉及调控dauer形成的基因的机制（年龄-1，daf-2，daf-Id和daf-28）和涉及影响发育和行为速度的基因的机制我们发现eat-2突变体的长寿命并不需要eat-16的活性，eat-2; DAF-2双突变体的寿命甚至比极长寿的DAF-2突变体更长，这些发现表明，食物限制通过与子体形成突变体不同的机制延长寿命。相比之下，我们发现，食物限制并不能进一步延长长寿突变体的寿命，这表明限制进食和热量限制影响相似的过程。
Low caloric intake (caloric restriction) can lengthen the life span of a wide range of animals and possibly even of humans, To understand better how caloric restriction lengthens life span, we used genetic methods and criteria to investigate its mechanism of action in the nematode Caenorhabditis elegans. Mutations in many genes (eat genes) result in partial starvation of the worm by disrupting the function of the pharynx, the feeding organ. We found that most eat mutations significantly lengthen life span (by up to 50%). In C, elegans, mutations in a number of other genes that can extend life span have been found. Two genetically distinct mechanisms of life span extension are known: a mechanism involving genes that regulate dauer formation (age-1, daf-2, daf-Id, and daf-28) and a mechanism involving genes that affect the rate of development and behavior (clk-1, clk-2, clk-3, and gro-1), We find that the long life of eat-2 mutants does not require the activity of DAF-16 and that eat-2; daf-2 double mutants live even longer than extremely long-lived daf-2 mutants, These findings demonstrate that food restriction lengthens life span by a mechanism distinct from that of dauer-formation mutants, In contrast, we find that food restriction does not further increase the life span of long-lived clk-1 mutants, suggesting that clk-1 and caloric restriction affect similar processes.