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September 03, 2012


'Epigenetics' Means What We Eat, How We Live And Love, Alters How Our Genes Behave



A mother rat withholds nurturing licks from its pup and elicits a brain change that impairs the pup's response to stress as an adult, researchers in Canada found. A pregnant woman's dietary deficits increase her offspring's risk of diabetes, stroke and heart disease later in life, researchers in England have shown


These startling scientific discoveries illuminate the emerging field of epigenetics, in which single nutrients, toxins, behaviors or environmental exposures of any sort can silence or activate a gene without altering its genetic code in any way.


Rather, the environmental exposure triggers a chemical change in the body or brain that mobilizes a group of molecules – called a methyl group. The methyl group attaches to the control segment of a gene and either silences – or alternately activates – the gene. Either way,, the gene veers off its intended course of activity.


a methyl group メチル基

Duke scientists describe methylation as putting gum on a light switch. The switch isn't broken, but the gum blocks its function.


We can no longer argue whether genes or environment has a greater impact on our health and development, because both are inextricably linked," said Randy Jirtle, Ph.D., a genetics researcher in Duke's Department of Radiation Oncology and initiator of the upcoming epigenetics conference. Co-initiator of the conference is Fred Tyson, Ph.D., at the National Institute of Environmental Health Sciences (NIEHS). "Each nutrient, each interaction, each experience can manifest itself through biochemical changes that ultimately dictate gene expression, whether at birth or 40 years down the road."

「遺伝子または環境が私たちの健康および発育により多くの影響を与えるかどうかはもはや議論する余地はないです、なぜならば、両方は密接に関係していますと」とデューク大学・放射線しゅよう学部の遺伝子研究者で来るべきエピジェネティックス創設者のRandy Jirtle, Ph.D博士は述べた。会議の共同創設者は米国国立環境衛生科学研究所のFred Tyson, Ph.D.博士です。「それぞれの栄養素、それぞれの相互作用、それぞれの経験は、誕生時または40才遡っても、究極に遺伝子発現を指示する生化学的変化を通じて現われる場合があります。

Such stealth changes often occur in embryonic or fetal development, but they set the stage for an adult's susceptibility to a host of diseases and behavioral responses, the data suggest. Moreover, epigenetic changes – so named because they sit on top of the gene and leave its sequence unchanged – can also be passed down from one generation to the next, said Jirtle.The good news is that methylation is potentially reversible, he said. Unlike defective genes, which are damaged for life, methylated genes can be demethylated. And, methyl tags that are knocked off can be regained via nutrients, drugs, and enriching experiences.


stealth changes ステルス変化
embryonic development 胚発生
fetal development 胎児発生
methylated genes メチル化された遺伝子

The fact that gene behavior is far more malleable than once believed has critically shifted the scientific community's course in mining the human genome, said Jirtle. No longer are mutant genes sought as the sole cause of disease. The dramatic rise in obesity, heart disease, diabetes and other conditions of prosperous nations are increasingly pegged as epigenetic in nature, and may well claim their origins in faulty embryonic development, he said.


embryonic development 胚発生
mutant gene 突然変異遺伝子

In one example, Jirtle showed that four common nutritional supplements – B12, folic acid, choline and betaine from sugar beets – fed to pregnant mice actually altered the coat colors of their offspring. One or several of the nutrients methlyated the mouse agouti gene and gave rise to mice with brown coats instead of yellow coats. More importantly, he said, the supplements lowered the offspring's adult susceptibility to obesity, diabetes and cancer as compared to the unsupplemented offspring.


agouti geneアグーチ遺伝子(毛色の遺伝子)
unsupplemented サプリメント不含
adult offspring 成体子孫

"Nutrition isn't a fleeting affair," said Jirtle. "We are, quite literally, what we eat as well as what our parents and even grandparents ate.


"In countries like India and China, undernutrition in one generation is followed by fat-laden fast foods the next," said Jirtle. "Children are set up in utero to experience an environment of low nutrition and find themselves in the land of plenty. The epigenetic software is programmed for one scenario but encounters another, often with disastrous results."


Undernutrition:低栄養状態, 栄養不足
in utero:子宮内の, 子宮内で

Seismic shifts in food sources, geographic locations, chemical exposures and even weather patterns can alter gene expression through epigenetic changes, he said.


seismic shift:地殻変動的な大転換

In Finland, researchers have linked an infant's low birth weight to the adult prevalence of coronary heart disease, diabetes, hypertension, stroke and even osteoporosis. David Barker's longitudinal studies have shown that low-weight newborns are biologically different for life than their bulkier counterparts. Smaller infants have fewer kidney nephrons, altered metabolism, and are more insulin resistant, said Barker, M.D., Ph.D., professor of medicine at Oregon Health and Sciences University. These deficits reflect a fetus' response to being undernourished, and they wire their genes to respond differently to the environment that follows outside the womb.

フィンランドで、研究者が低体重出生児を冠性心疾患、糖尿病、高血圧症、脳卒中および骨粗鬆症などの成人の発症率と関連付けた。David Barker'sの経年的研究は低体重新生児が太った新生児より一生にわたり生物学的に異なることを示しました。小さな幼児は腎臓ネフロンが少なくて、代謝異常で、インスリン抵抗性が高くいなりますと、オレゴン健康科学大学医学部教授のBarker, M.D., Ph.D.博士は述べました。これらの不足は栄養不良であることへの胎児反応を反映していて、それらは子宮外次の環境に対して異なる反応をするように遺伝子を配線します。

infant's low birth weight 低体重出生児
stroke 脳卒中
longitudinal studies 経年的研究;
altered metabolism 代謝異常
insulin resistant インスリン抵抗性

"The notion that heart disease is solely about middle-aged men's behavior is obsolete," said Barker, one of 70 speakers presenting data at the upcoming conference. "A huge body of evidence now supports the notion that these diseases are linked to poor fetal growth followed by adequate or even an excess of food in childhood. While we are not doomed by our prenatal and early nutritional exposures, they do make us more vulnerable to disease," said Barker, whose latest results will be published in the October 27, 2005, issue of the New England Journal of Medicine.


poor fetal growth 胎児の成長不全

Nutrition is only one player in the epigenetic repertoire. Behaviors have a direct impact on brain wiring, said Moshe Szyf, Ph.D., Professor of Pharmacology and Therapeutics at McGill University in Montreal and a presenter at the conference. Maternal care, for example, has long been known to affect behavioral outcomes of children, as exemplified by orphans who grow up neglected or impoverished. But Szyf and his collaborator Michael Meaney at McGill University have linked maternal grooming behaviors in rats to a specific brain change in the glucocorticoid receptor, which controls the level of stress hormone released by the adrenal glands. Rats that were not properly licked -- a rodent's form of nurturing -- produce more stress hormones as adults. Syzf identified the mechanism behind this effect as a loss of methylation in the part of the glucocorticoid receptor gene that controls its expression.


Maternal care 母親の育て方
maternal grooming behaviors母親によるグルーミング行動
glucocorticoid receptor グルココルチコイド受容体

"We're showing that it's the maternal behavior that counts, not just the genetic baggage," he said. "Behavior can clearly affect the chemistry of DNA."


maternal behavior 母性行動

Szyf's team was able to remethylate the glucocorticoid receptor gene by injecting an essential amino acid, methionone, into the brains of well nurtured rats. The scientists successfully turned the good stress responders into less healthy stress responders, and vice versa by injecting a different compound into the brains of poor responders.


Methionine:メチオニン(必須アミノ酸のひとつで、側鎖に硫黄を含んだ疎水性のアミノ酸である。 血液中のコレステロール値を下げ、活性酸素を取り除く作用がある。メチオニンは、牛や豚などの赤肉、魚、豆類、卵、ニンニク、玉ねぎ、ヨーグルトなどに含まれます。

The reversible nature of epigenetic changes has its down sides, as well. Exposures to pesticides, toxins and synthetic compounds can methylate genes in adulthood and give rise to a host of diseases – such as cancer and asthma -- whose prevalence has soared in recent decades, said H. Kim Lyerly, M.D., director of the Duke Comprehensive Cancer Center. Pesticides encountered in utero might be dormant in the fetus, only to cause cancer ten, 20 or 50 years later, he said.

エピジェネティックな変化の可逆的性質は同様にその下方性の側面があります。殺虫剤、毒物および合成化合物の暴露は成人の遺伝子をメチル化して、有病率が最近数十年間に急上昇したがんや喘息などの宿主の病気の上昇を生じさせたとデューク総合がんセンターの部長、H. Kim Lyerly, M.D博士は述べた。子宮内で遭遇した殺虫剤は胎児内に潜伏しているかもしれないが、10、20あるいは50年後に残念なことにがんを引き起こすことになりうつと彼は言いました。

reversible nature 可逆的性質
synthetic compounds 合成化合物
prevalence 有病率

Even the lowest detectable limits of a chemical can have dire effects on a living organism, added William Schlesinger, Ph.D., Dean of the Nicholas School of the Environment and Earth Sciences at Duke. Atrizine is a prime example. Less than one part per billion of this widely used corn herbicide de-masculinizes developing frogs or causes dual male-female genitalia. Yet often the Environmental Protection Agency's instrumentation doesn't record such minute levels of chemical exposure, he said.

化学薬品の最低検知限界値でさえ生存生物に直接的影響を及ぼすことになるとデューク大学Nicholas School of the Environment and Earth Sciences学部長William Schlesinger, Ph.D.博士は付け加えた。アトラジン(除草剤)は典型的な例です。この広く使用されているトウモロコシ用除草剤の10億分の1より少なくても発育中のカエルの雄性を取り除くまたは

detectable limits 検知限界値
living organism:生存生物

"If Atrizine is having this effect in animals, we question its effects on humans," said Schlesinger. "Are the current standards of exposure high enough to protect the organisms exposed to select chemicals? Our role as environmental scientists is to assess the potential impact of each compound on native organisms and develop models that physician scientists can apply to humans."


At the NIEHS, scientists have embraced epigenetics as a major frontier in their scientific exploration of the environment, said David Schwartz, Ph.D., the institute's director."Epigenetics represents a huge opportunity to study an alternative pathway that explains why individuals respond differently to environmental cues," said Schwartz. "This field provides the missing link between the environment and the development of diseases that goes beyond many of the subtle changes in DNA that explain only a fraction of the diseases humans develop."

米国国立環境衛生学研究所で、科学者は環境の科学探査で主なフロンティアとしてエピジェネティックスを抱合したと、研究所の所長のDavid Schwartz, Ph.D.博士は述べた。「エピジェネティックスは、なぜ個人が環境要因に異なって応答するか説明する代替経路の研究にとても大きな機会を意味しますと」Schwartz.は述べた。「この分野は、環境とヒトが発症する一部の病気だけを説明するDNAにおける多くの微細な変化を越える病気の発症とのミッシング・リンク(失われた環・鎖)を提供します。」

missing link:ミッシング・リンク(失われた環・鎖)
scientific exploration 科学探査
environmental cue 環境要因





The genome dynamically responds to the environment. Stress, diet, behavior, toxins and other factors activate chemical switches that regulate gene expression.














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