Breaking the bonds of genetic destiny

The conventional view of genetics is steeped in fatalism. 沙巴体育APP从父母那里继承了一种独特的基因密码,无论好坏,这种DNA是不可改变的. 有些疾病像燎原之火一样在家庭中蔓延——不可避免且不可阻挡. High blood pressure, cancer, dementia — inextricably woven into familial double helixes like barbed wire.

Researcher Moshe Szyf and his contribution to Epigenetics
Researcher Moshe Szyf
但是,如果沙巴体育APP强迫自己每周上三次有氧运动课,每天吃四份蔬菜,而不仅仅是推迟了不可避免的事情,那该怎么办呢? What if, on top of the immediate health benefits, both activities actually modify the expression of our DNA, 使问题基因失去活性,这些基因会绊倒沙巴体育APP,让沙巴体育APP跌跌撞撞地走向心血管疾病或阿尔茨海默氏症? And imagine if, in so altering that genetic expression, 沙巴体育APP能够将一种基因密码传递给沙巴体育APP的后代最终摆脱了潜伏在暗处的怪物.

这些都是沙巴app下载药理学教授Moshe Szyf 30年来一直在问的问题. 他开创性的研究已经证明,尽管沙巴体育APP的DNA在受孕时几乎是锁定的, 暴露在毒素和营养等外部因素下,会在沙巴体育APP体内引发化学反应,从而永久改变沙巴体育APP基因的反应方式. Once triggered, 一组被称为甲基的分子会附着在基因的控制中心, 完全关闭它——在不改变DNA序列的情况下改变基因功能. Welcome to the world of epigenetics.

科学证据表明,这种由环境触发的基因表达, or epigenetic imprint, might have repercussions far beyond the immediate host body. 这可以解释为什么二战期间营养不良的荷兰妇女所生的体重过轻的婴儿在战争和食物配给结束几十年后长大,生出体重过轻的孩子. 最近的研究表明,在进入青春期之前就开始吸烟的男性的儿子更容易肥胖. Clearly, 发生在两个原始父母群体中的表观遗传变化对后代产生了持久的不利影响. “诀窍在于,”Szyf说,“能够控制你激活和关闭的东西."

As Szyf sees it, 如果暴露在环境中会引发基因的化学变化从而导致疾病的发生, 也许研究人员可以在药理学上操纵同样的机制来逆转这种疾病. For example, in certain types of cancer, 正常情况下抑制肿瘤生长的基因被关闭,而其他促进转移的基因则被关闭, or the spread of cancer, are turned on. Szyf的团队目前正在测试两种癌症药物,它们可以重新激活这种休眠基因,以及可以沉默转移基因的药物.

Well-groomed rats are happy rats

Researcher Michael Meaney and his contribution to Epigenetics
Michael Meaney, associate director of research at Douglas Hospital
In 2003, Szyf and Michael Meaney, associate director of research at the Douglas Hospital, 研究发现,在幼鼠时期接受过母亲适当的舔舐和梳理的幼鼠,成年后会比未接受过梳理的幼鼠平静得多. Of course, 这本身并不是什么惊天动地的事情——人们早就认识到,母亲的照顾对一个人的发展有持久的影响. "The question then becomes why the change in behaviour?" says Meaney.

Meaney证明,母亲的舔舐刺激了大脑中糖皮质激素受体的化学变化, 调节大鼠肾上腺释放多少压力荷尔蒙的机制. 幼鼠接受的梳理越少,成年后产生的压力荷尔蒙就越多.

By administering methionine, an essential amino acid, to the brains of well-adjusted rats, Szyf能够改变它们各自的糖皮质激素受体的表达,这样它们就能反映出那些养育较少的表亲. The result? 应激激素的分泌增加,原先懒散的啮齿动物明显变得更加疲惫. Similarly, 沙巴app下载大学的研究小组通过对产生同一种激素的基因进行药理操作,降低了焦虑大鼠体内同一种激素的水平. The implications of these findings are enormous, 这表明,类似的相互作用可以用来对抗抑郁症的破坏, schizophrenia and other brain disorders.

Med schools revamped

Although creating new drugs for diseases is exciting, the potential of epigenetics extends beyond the pharmacy. “当然,沙巴体育APP可以考虑开发出能产生这些效果的药物,”Meaney说. "But if the initial effect was laid down in response to social stimulus, 那么有没有可能某种社会经验可以逆转这一过程呢?"

In a country propping up an increasingly fragile health care system, epigenetics may force politicians to rethink their economics. Although the field is still developing, 越来越多的证据表明,营养等各种各样的社会和环境因素, pollutants, 住房和儿童保育将对现在和今后几代加拿大人的健康产生重大影响. “如果沙巴体育APP真的想加强沙巴体育APP的经济,以及经济中个人的健康和表现, then we need to focus on early development and the quality of family life," says Meaney.

表观遗传学研究可能带来的最激进的发展可能是医学教学的方式. 医学院将被要求开放更多的课程,包括更多的艺术和人文学科,跨学科合作将变得越来越必要. Abe Fuks, Dean of Medicine, 认为药理学家Szyf和心理学家Meaney所做的工作是新研究方向的象征——这是该大学一段时间以来一直在前进的方向. “沙巴app下载大学的最大优势之一一直是它能够将极高的研究标准与这种开放和合作相结合," he says "This is a wonderful example for others to follow."

This story originally appeared in the McGill Reporter.

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