【科普】氨基酸作为小鼠长寿“仙丹”的科学依据

来源:百度文库 编辑:神马文学网 时间:2024/04/29 21:30:35
2010-10-08 11:56
氨基酸作为小鼠长寿“仙丹”的科学依据

本文引用地址:http://www.sciencenet.cn/m/user_content.aspx?id=370801
《细胞——代谢》最近发表了意大利科学家的最新研究结果,初步证明支链氨基酸(亮氨酸、异亮氨酸和缬氨酸等)可以使小鼠寿命延长12%!相应地,此前美国科学家也曾在酵母中获得类似结果。但是,迄今为止还没有报道指出氨基酸对人类寿命有何影响。这样看来,我们目前还只能说氨基酸肯定是人类营养添加剂,但不能断言它们也是人类的长寿“仙丹”!
这篇文章的题目是“支链氨基酸在中年小鼠中促进存活并维持心肌与骨骼肌线粒体生物发生”(Branched-Chain Amino Acid Supplementation Promotes Survival and Supports Cardiac and Skeletal Muscle Mitochondrial Biogenesis in Middle-Aged Mice),其主要研究结果是发现支链氨基酸能延长雄性小鼠的平均寿命、激活mTOR及eNOS信号转导通路、强化中年小鼠线粒体生物发生及活性氧清除系统功能、改善年龄增长引起的肌肉损害等(附图)。

图解及注释:红色如地毯者代表一个心肌细胞(Cardiomyocytes)或骨骼肌纤维(Skeletal muscle fibers);蓝色如蚕蛹者代表线粒体(Mitochondria),其功能是消耗氧气产生能量(ATP),同时也会释放活性氧(ROS);黄色如卵黄者代表细胞核(Nucleus),显示了活性氧保护系统(ROS defense system)和线粒体基因表达(Mitochondrial gene expression);箭头所指为支链氨基酸(Branched-chain amino acids)激活哺乳类雷帕霉素靶点(mTOR)-内皮型一氧化氮合酶(eNOS)-一氧化氮(NO)信号转导通路-基因表达级联。
许多证据显示,线粒体的生物发生越频繁,真核细胞存活的时间就越长。这是因为线粒体的功能与细胞寿命存在着密切关系,一般衰老细胞的线粒体数目减少,而活性氧自由基水平增高。相反,支链氨基酸不仅能大幅增加心肌及骨骼肌细胞中的线粒体数目,而且还能上调活性氧自由基清除系统的基因表达,进而整体提高细胞的抗衰老、抗胁迫能力,于是细胞乃至整个机体的寿命也就相应延长了。
有趣的是,适度节食及锻炼同样能延长哺乳动物的寿命,其机理也是减少活性氧自由基对细胞的损害。
从古至今人类一直都在追求长生不老,如今这个梦想似乎不再遥不可及了。据英国《每日电讯报》10月5日报道,科学家发现了一种能够延年益寿的药物,而且已经在小白鼠身上进行实验,首次获得成功。
这种神奇的药物就是由亮氨酸、异亮氨酸和缬氨酸这3种氨基酸组成的混合物,学名“支链氨基酸”。在实验过程中,研究人员给被试小白鼠喝的水里加入了这3种氨基酸,结果发现它们的寿命平均达到了869天,而普通小白鼠则只能存活大约774天。也就是说,“支链氨基酸”使小白鼠的生命延长了12%。
在延长寿命的同时,小白鼠的机体内还发生了一系列积极的生物反应,比如细胞得以摄取更多的能量、自由基减少等。自由基是机体氧化反应中产生的有害化合物,具有强氧化性,可损害机体的组织和细胞,进而引起慢性疾病及衰老效应。经过这些体内变化,小白鼠看起来充满活力,而且肌肉协调能力有所提高。
研究人员介绍说,“支链氨基酸”是一种十分重要和有效的营养补剂,它可以帮助生物体自然地、没有任何副作用地增强肌肉或获得更多能量。去年,科学家已经发现这种氨基酸混合物在延长单细胞酵母寿命上的巨大作用。
“人类首次证明了氨基酸混合物能够延长小白鼠的寿命,”这项研究的主要研究员、来自意大利米兰大学的恩佐·尼索里教授表示。他还指出,如果在此基础上发明氨基酸补剂,那么它很可能在未来造福人类,对于老年人或病人有很大帮助,尤其是那些患有以细胞能级降低为特征的疾病的人,比如心力衰竭或慢性肺病患者等。
这个新学说已经刊登在新一期的美国科学杂志《细胞—代谢》(Cell Metabolism)上。
前不久,俄罗斯科学家弗拉基米尔·斯库拉乔夫宣布,他研制出一种可以抗衰老的药物,有望两年内投入市场。他自称这种新药能够消除氧化对人体的负面影响,避免患上老年病,从而延长寿命多达数十年。
A genuine 'elixir of life' - at least for mice
A genuine "elixir of life" that can hold death at bay has been discovered by scientists.
By Richard Alleyne, Science Correspondent
Published: 6:00PM BST 05 Oct 2010
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The treated mice had more stamina and improved muscle co-ordination Photo: ALAMY
The cocktail of amino acids - building blocks of proteins - was found to increase the lifespan of mice by 12 per cent.
Researchers believe it may also benefit humans, especially the elderly or sick.
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The animals lived significantly longer than other mice fed a normal diet.
Their lifespan range had a midpoint of 869 days compared with 774 days for untreated mice, a difference of 12 per cent.
Longer survival was accompanied by biological changes which boosted the energy supply to cells and reduced oxidative damage caused by destructive molecules called free radicals.
The treated mice had more stamina and improved muscle co-ordination.
"This is the first demonstration that an amino acid mixture can increase survival in mice," said study leader Dr Enzo Nisoli, from the University of Milan in Italy.
Last year scientists showed that the same amino acids, leucine, isoleucine and valine, could extend the lifespan of single-celled yeast.
The new findings, reported in the journal Cell Metabolism, raise the possibility of amino acid supplements benefiting humans.
The scientists pointed out that the mice studied were aged but otherwise healthy.
They believe taking the amino acids might be especially helpful for the elderly or ill, particularly people with heart failure, chronic lung disease, or other conditions characterised by flagging energy levels.
Dr Nisoli said a large patient trial was needed to provide evidence convincing enough for doctors. However, there was little financial incentive for companies to conduct such studies on dietary supplements.
Leucine, isoleucine and valine, known as branched-chain amino acids (BCAAs), account for a fraction of the 20 amino acids from which proteins are made, but appear to have special anti-ageing properties.
Mice given the three amino acids produced larger numbers of mitochondria - the rod-like "powerhouses" in cells that generate energy - in their heart and skeletal muscle.
They also showed increased activity of SIRT1, a well-known longevity gene, and developed better defences against free radicals.
BCAA nutritional supplements are readily available in health food stores and online.
Amino acid supplements were likely to be more effective than consuming proteins containing the same amino acids, according to the researchers.
Unlike protein, they did not have to be digested, and could enter the bloodstream immediately.
"They come with no energy cost," said Dr Nisoli.
In their paper the scientists wrote: "We have provided evidence that an original BCAA mixture increases average life span in male mice.
"This was likely the consequence of increased mitochondrial biogenesis and reduced oxidative stress in cardiac and skeletal muscles.
Our study offers a rationale for deeply exploring the role of amino acids in prevention and
control of age-related disorders in humans."
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