|
科学家发现少食而长寿的基因,人类有望改善寿命期限 Gene Links Longevity and Diet, Scientists Say By NICHOLAS WADE Published: May 3, 2007 Scientists have identified a gene that makes roundworms live longer when they eat less, a finding they hope could lead to drugs that promote human longevity, but without the pain of strict dieting. Roundworms are excellent subjects for longevity research because they usually only live three weeks, making any increment in lifespan quickly apparent. Although people and worms took divergent evolutionary paths some 600 million years ago, they retain many genetic mechanisms in common, including the insulin-signaling control of metabolism and, quite possibly, the ancient survival mechanism of living longer to ride out famines. This mechanism has been retained by mice, which live a third longer if fed a healthy but very low-calorie diet. Most people find it impossible to stay on such a diet, so researchers would like to stimulate the life-extension mechanism with a drug instead. But first they need to identify the genetic pathway through which the mechanism is set off so that possible drugs can be tested first in mice and then, perhaps, in people. Disrupting a gene that mediates the insulin-signaling pathway in roundworms is one way of making them live longer. But researchers have been unsure whether this is the pathway involved in achieving the low-calorie/longer-life effect. In what may prove to be a major clarification of the issue, researchers at the Salk Institute for Biological Studies reported in today’s issue of the journal Nature the existence of a life-extending genetic pathway, which they believe is the one naturally set off by dietary restriction. The Salk Institute team, led by Siler Panowski and Andrew Dillin, said the new pathway is mediated by a gene already known from its role in building the worm’s gut while the worm is an embryo. This new pathway works independently of the insulin-signaling pathway, they said, although it shares several genetic elements, and is dedicated just to the famine response. “This may be the primordial gene that regulates nutrients and helps the animal live a long time through dietary restriction,” Dr. Dillin said. “We think it likely to play a role in the human condition.” The gene has exact counterparts in mammals, three of them, in fact, because the gene tripled at some point in mammalian evolution. The three genes in mice and in people are known as FoxA 1, 2 and 3. The Fox genes are a large family of master regulator genes that control other genes. The Salk Institute has applied for a patent based on use of the FoxA genes, Dr. Dillin said. Klaus H. Kaestner, a researcher at the University of Pennsylvania who has long studied the FoxA genes, said the finding was “very significant and will open new avenues for investigation.” For his own work, Dr. Kaestner has already engineered strains of mice in which the FoxA-1 and FoxA-2 genes can be switched off. He said he had shipped some of the mice to the Salk Institute team, which will test whether the FoxA genes mediate the diet-related longevity response in mice. If mice on restricted diets do not live longer when their FoxA gene is switched off, that would indicate the genes play an essential role in extending the life of the mice. Leonard Guarente, a longevity researcher at the Massachusetts Institute of Technology, said the newfound role of the worm gene was not the only mechanism involved in life extension and that “the way in which it will fit into the whole story is not clear yet.” After many decades of being regarded among scientists as a backwater, research on longevity has been enjoying renewed interest. The stakes are high: a drug that mimicked the effects of caloric restriction in people could lead to significant increases in lifespan. But much work remains to be done in roundworms and mice to define the genetic pathway and its possible side effects in people, like reduced fertility. renling本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领 Scientists have identified a gene that makes roundworms live longer when they eat less, a finding they hope could lead to drugs that promote human longevity, but without the pain of strict dieting.科学家在蛔虫体内发现了一个基因，当蛔虫进食少时，它可以发挥作用，使蛔虫延长寿命。这个发现使科学家希望可以根据这个基因发明药物，使人在不节食的条件下，增加人类的寿命。 Roundworms are excellent subjects for longevity research because they usually only live three weeks, making any increment in lifespan quickly apparent. Although people and worms took divergent evolutionary paths some 600 million years ago, they retain many genetic mechanisms in common, including the insulin-signaling control of metabolism and, quite possibly, the ancient survival mechanism of living longer to ride out famines.蛔虫是研究长寿的最佳对象，因为他们通常只能活3周，任何寿命的增加都很快的显现出来。虽然在60亿年前，人类和蠕虫进行了不同的进化，但他们仍然在遗传机制上保持了很多的相同点。包括胰岛素信号控制机制，很可能也包括度过饥饿期后寿命增加机制。 This mechanism has been retained by mice, which live a third longer if fed a healthy but very low-calorie diet. Most people find it impossible to stay on such a diet, so researchers would like to stimulate the life-extension mechanism with a drug instead. But first they need to identify the genetic pathway through which the mechanism is set off so that possible drugs can be tested first in mice and then, perhaps, in people. 这种机制在老鼠体内得到保留，如果给老鼠喂低卡路里并且健康的食物，可以延长老鼠三分之一的寿命。大多数人发现人类不可能坚持这样的饮食，所以研究者希望用药物使生命延长机制发挥作用。但是他们首先要确定基因通路，通过开启和关闭基因通路，才能在老鼠体内进行药物实验，然后，可能在人体内实验。 Disrupting a gene that mediates the insulin-signaling pathway in roundworms is one way of making them live longer. But researchers have been unsure whether this is the pathway involved in achieving the low-calorie/longer-life effect.破坏蛔虫体内胰岛素信号通路是延长蛔虫寿命的一种方法，但是科学家还不能确定这个通路是否包括在低卡路里/增加寿命的机制中。 In what may prove to be a major clarification of the issue, researchers at the Salk Institute for Biological Studies reported in today’s issue of the journal Nature the existence of a life-extending genetic pathway, which they believe is the one naturally set off by dietary restriction.是什么原因使寿命延长机制起作用是一个需要证明的重要问题，Salk Institute的研究者在today’s issue of the journal Nature发表文章，认为节食是受命延长基因通路的自然启动点。 The Salk Institute team, led by Siler Panowski and Andrew Dillin, said the new pathway is mediated by a gene already known from its role in building the worm’s gut while the worm is an embryo. This new pathway works independently of the insulin-signaling pathway, they said, although it shares several genetic elements, and is dedicated just to the famine response. Siler Panowski和Andrew Dillin领导的索尔克学院研究团队认为，在蠕虫的胚胎期，基因就开始对这个新的通路进行调解，且该基因对通路得调节不同于对蠕虫肠道形成的调节。这个新的通路不依赖于胰岛素信号传递系统，他们说，虽然这个通路与其他基因有共同的遗传基础，但是该通路只对饥饿起反应。 “This may be the primordial gene that regulates nutrients and helps the animal live a long time through dietary restriction,” Dr. Dillin said. “We think it likely to play a role in the human condition.” Dr. Dillin说这可能是一个原始的营养调节基因，通过饮食限制增加寿命，我们认为它也同样在人类中起作用。 The gene has exact counterparts in mammals, three of them, in fact, because the gene tripled at some point in mammalian evolution. The three genes in mice and in people are known as FoxA 1, 2 and 3. The Fox genes are a large family of master regulator genes that control other genes. 在哺乳动物存在这个基因相应基因，并且在哺乳动物这个基因有三个，因为在某些进化点上使这个基因增至三倍，这三个基因在人和老鼠体内分别为FoxA 1, 2 和3，Fox是一个大的基因家族，可以通过控制调节基因来调节其他基因的表达。 The Salk Institute has applied for a patent based on use of the FoxA genes, Dr. Dillin said. Dr. Dillin说，索尔克学院已经对FoxA基因的应用申请了专利。 Klaus H. Kaestner, a researcher at the University of Pennsylvania who has long studied the FoxA genes, said the finding was “very significant and will open new avenues for investigation.” 宾西法尼亚大学的研究者，Klaus H. Kaestner长期研究FoxA基因，他说，这个基因很重要，给我们的研究提供了新的方向。 For his own work, Dr. Kaestner has already engineered strains of mice in which the FoxA-1 and FoxA-2 genes can be switched off. He said he had shipped some of the mice to the Salk Institute team, which will test whether the FoxA genes mediate the diet-related longevity response in mice. If mice on restricted diets do not live longer when their FoxA gene is switched off, that would indicate the genes play an essential role in extending the life of the mice. Dr. Kaestne已经构建了几只工程鼠，他们的FoxA-1 和FoxA-2基因可以启动和关闭，他说他已经送了几只这样的老鼠给索尔克学院的研究团队，这些老鼠用来研究FoxA基因是否在饮食相关的寿命调节中起作用。如果在FoxA不表达的老鼠，虽然限制饮食，但是也没有增长寿命，就说明FoxA在延长老鼠寿命的过程中起本质作用。 Leonard Guarente, a longevity researcher at the Massachusetts Institute of Technology, said the newfound role of the worm gene was not the only mechanism involved in life extension and that “the way in which it will fit into the whole story is not clear yet.” Leonard Guarente，一个马赛诸塞科技大学的研究者，认为这个蠕虫基因的发现不仅仅局限于延长寿命，是否可以应用于其他方面还不得而知。 After many decades of being regarded among scientists as a backwater, research on longevity has been enjoying renewed interest. 在几十年认为寿命延长是一个误区后，科学家现在又对寿命延长充满信心。 The stakes are high: a drug that mimicked the effects of caloric restriction in people could lead to significant increases in lifespan. But much work remains to be done in roundworms and mice to define the genetic pathway and its possible side effects in people, like reduced fertility. 其应用价值很高，一个用来模拟热量限制的药物，可以增加人的寿命，但是为了确定蠕虫和老鼠体内的基因通路，还有很多工作需要做，并且对于人类，它是否有类似于缺乏营养的副作用也需要进一步研究。 科学家在蛔虫体内发现了一个基因，当蛔虫进食少时，它可以发挥作用，使蛔虫延长寿命。这个发现使科学家希望可以根据这个基因发明药物，使人在不节食的条件下，增加人类的寿命。蛔虫是研究长寿的最佳对象，因为他们通常只能活3周，任何寿命的增加都很快的显现出来。虽然在60亿年前，人类和蠕虫进行了不同的进化，但他们仍然在遗传机制上保持了很多的相同点。包括胰岛素信号控制机制，很可能也包括度过饥饿期后寿命增加机制。这种机制在老鼠体内得到保留，如果给老鼠喂低卡路里并且健康的食物，可以延长老鼠三分之一的寿命。大多数人发现人类不可能坚持这样的饮食，所以研究者希望用药物使生命延长机制发挥作用。但是他们首先要确定基因通路，通过开启和关闭基因通路，才能在老鼠体内进行药物实验，然后，才能在人体内实验。破坏蛔虫体内胰岛素信号通路是延长蛔虫寿命的一种方法，但是科学家还不能确定这个通路是否包括在低卡路里/增加寿命的机制中。是什么原因使寿命延长机制起作用是一个需要证明的重要问题，Salk Institute的研究者在today’s issue of the journal Nature发表文章，认为节食是受命延长基因通路的自然启动点。Siler Panowski和Andrew Dillin领导的索尔克学院研究团队认为，在蠕虫的胚胎期，基因就开始对这个新的通路进行调解，且该基因对通路的调节不同于对蠕虫肠道形成的调节。这个新的通路不依赖于胰岛素信号传递系统，他们说，虽然这个通路与其他基因有共同的遗传基础，但是该通路只对饥饿起反应。Dr. Dillin说这可能是一个原始的营养调节基因，通过饮食限制增加寿命，我们认为它也同样在人类中起作用。在哺乳动物存在这个基因相应基因，并且在哺乳动物同样的基因有三个，因为在某些进化点上使这个基因增至三倍，这三个基因在人和老鼠体内分别为FoxA 1, 2 和3，Fox是一个大的基因家族，可以通过控制调节基因来调节其他基因的表达。Dr. Dillin说，索尔克学院已经对FoxA基因的应用申请了专利。宾西法尼亚大学的研究者，Klaus H. Kaestner长期研究FoxA基因，他说，这个基因很重要，给我们的研究提供了新的方向。Dr. Kaestne已经构建了几只工程鼠，他们的FoxA-1 和FoxA-2基因可以启动和关闭，他说他已经送了几只这样的老鼠给索尔克学院的研究团队，这些老鼠用来研究FoxA基因是否在饮食相关的寿命调节中起作用。如果在FoxA不表达的老鼠，虽然限制饮食，但是也没有增长寿命，就说明FoxA在延长老鼠寿命的过程中起本质作用。一个马赛诸塞科技大学的研究者，认为这个蠕虫基因的发现不仅仅局限于延长寿命，是否可以应用于其他方面还不得而知。在几十年认为寿命延长是一个误区后，科学家现在又对寿命延长充满信心。其应用价值很高，一个用来模拟热量限制的药物，可以增加人的寿命，但是为了确定蠕虫和老鼠体内的基因通路，还有很多工作需要做，并且对于人类，它是否有类似于缺乏营养的副作用也需要进一步研究。 请专家莅临指导！！ |
|
|
