活到“140岁”:小鼠是如何做到的?

2016-08-26 佚名 药明康德

衰老是导致很多疾病发生的首要因素之一,包括心脏病、关节炎、癌症和老年痴呆。通过延缓衰老的过程,我们也许可以减少上述疾病的发生,最终做到延年益寿。这无疑是很多人的梦想。如今,这一梦想率先在小鼠身上实现,而采取的手段似乎并不复杂:一个是节食;另一个是免疫抑制药物雷帕霉素(rapamycin)。▲雷帕霉素结构(图片来源:维基百科)先说节食。最近,来自荷兰鹿特丹伊拉斯谟大学(Erasmus Univers

衰老是导致很多疾病发生的首要因素之一,包括心脏病、关节炎、癌症和老年痴呆。通过延缓衰老的过程,我们也许可以减少上述疾病的发生,最终做到延年益寿。这无疑是很多人的梦想。如今,这一梦想率先在小鼠身上实现,而采取的手段似乎并不复杂:一个是节食;另一个是免疫抑制药物雷帕霉素(rapamycin)。

▲雷帕霉素结构(图片来源:维基百科)

先说节食。最近,来自荷兰鹿特丹伊拉斯谟大学(Erasmus University)的科学家发现了节食对一类天生早衰的小鼠十分显着的延长寿命作用。这类小鼠的ERCC1和ERCC5基因存在缺陷,使得其体内细胞DNA修复的功能大大削弱,其寿命通常只有4-6个月。这时,长片段基因上出现可阻遏转录的突变的几率明显增长,从而随之导致表达量显着下降。研究人员发现,如果将上述早衰小鼠的食量减少30%,它们的寿命则会延长至原来的三倍!同时,它们体内细胞长基因的转录得到了有效恢复,且神经元和运动机能得到了更好的保持。

在这一发表于近期的《Nature》期刊的工作中,研究者们表示,上述小鼠可作为研发食疗干预以及早衰症治疗方法的有效模型。

也许有不少人早已听说节食可能的保健效果。不过,要说到雷帕霉素与延年益寿之间的关系,很多人恐怕还未曾耳闻。雷帕霉素本是用于抑制器官移植后免疫排斥反应的一种药物。如今,越来越多的证据表明,雷帕霉素可能具有延长小鼠寿命的功能。

来自华盛顿大学等机构的科学家们对此进行了系统的研究。他们对20个月大的小鼠(相当于人类的60到65岁年龄)按照8 mg/kg的剂量施用了连续90天的雷帕霉素,结果发现这使得它们的寿命要比对照小鼠延长近60%,而且更加的“年轻态”。其中,一个名为Ike的小鼠活了总共1400天,相当于人类寿命的140岁!这是迄今为止延长正常小鼠寿命幅度最大的单个干预手段。该成果发表于近期的《eLIFE》期刊上。

▲文章通讯作者Matt Kaeberlein教授(图片来源:华盛顿大学官网)

“这是一个令人惊奇的结果。短期施用雷帕霉素竟对个体的健康和存活产生如此持续性的影响,即便在停止药物使用后。”文章的通讯作者Matt Kaeberlein教授说道,尽管研究者们对雷帕霉素究竟如何起到延长寿命的机制尚不明确。

另一方面,雷帕霉素的效果并不总是有益的。研究者发现,高剂量的雷帕霉素会增加雌性小鼠患恶性血液肿瘤的风险,而对雄性小鼠则没有受到上述影响。此外,小鼠的肠道菌群也会被雷帕霉素改变,表现为肠道分节丝状菌(SFB)的比例明显升高。

▲肠道分节丝状菌(图片来源:sciencedaily)

“如此短暂干预手段的成功有着很高转化医学价值,”Matt Kaeberlein教授说道:“人们显然更容易接受一种只需从中年开始接受有限时程的疗法,而不是一个需要终生使用的药物。”

参考资料:

[1] Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice

[2] Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice

[3] Brief rapamycin therapy in middle-aged mice extends lives

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    2016-08-28 xiaotaiyang1

    抗衰老啊

    0

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    2016-08-26 Guoxj3234

    学习起来

    0

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    2016-08-26 doctorJiangchao

    值得收藏

    0

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    2016-08-26 doctorJiangchao

    继续学习

    0

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    2016-08-26 doctorJiangchao

    继续关注

    0

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镁是人体必需的矿物元素,因为镁在人体的含量较多,故被成为常量元素。镁主要分布于细胞内,细胞外液的镁不超过1%。人体内血清镁离子(Mg2+)对于细胞增长和维护正常的细胞过程是至关重要的。但是,对于妊娠期这个特殊时期,孕妇体内血清镁离子(Mg2+)又是如何影响胎儿的生长和发育的呢?目前临床或是研究上对于该问题的探究是凤毛麟角少之又少。近期Shlegel RN等人对该领域进行了探究,通过对小鼠进行研究,

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