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December 20, 2015

孤独は病気の原因となる細胞変化を引き起こすことになりますと研究は示してます。Science dailyより

Loneliness triggers cellular changes that can cause illness, study shows


孤独は病気の原因となる細胞変化を引き起こすことになりますと研究は示しています。Science dailyより

Loneliness is more than a feeling: For older adults, perceived social isolation is a major health risk that can increase the risk of premature death by 14 percent.


premature death 早期死亡

Researchers have long known the dangers of loneliness, but the cellular mechanisms by which loneliness causes adverse health outcomes have not been well understood. Now a team of researchers, including UChicago psychologist and leading loneliness expert John Cacioppo, has released a study shedding new light on how loneliness triggers physiological responses that can ultimately make us sick.

研究者達は長い間孤独の危険性を知っていましたが、孤独が有害な健康結果を引き起ことになる細胞メカニズムは良く理解されていなかった。今、シカゴ大学の心理学者で著名な孤独の専門家、ジョン・T. カシオポを含む研究者のチームは、孤独が最終的に私たちが病気になる生理学的応答を引き起こす方法に新たな光をあてている研究をリリースしました。

The paper, which appears Nov. 23 in the Proceedings of the National Academy of Sciences, shows that loneliness leads to fight-or-flight stress signaling, which can ultimately affect the production of white blood cells.


Proceedings of the National Academy of Sciences 米国科学アカデミー紀要
fight-or-flight 闘争 逃走反応
stress signaling ストレスシグナル伝達

Along with Cacioppo, the research team includes Steven W. Cole of UCLA and John P. Capitanio of the California National Primate Research Center at the University of California, Davis. The study examined loneliness in both humans and rhesus macaques, a highly social primate species.

カシオポともに、研究チームは、カリフォルニア大学ロサンゼルス校・Steven W. Coleおよびカリフォルニア大学デービス校、カリフォルニア国立霊長類研究センター・John P. Capitanioが含まれています。研究は、ヒトと特に社会的霊長類のアカゲザルの両方で孤独を調査した。

California National Primate Research Center カリフォルニア国立霊長動物研究センター
rhesus macaques アカゲザル

Previous research from this group had identified a link between loneliness and a phenomenon they called "conserved transcriptional response to adversity" or CTRA. This response is characterized by an increased expression of genes involved in inflammation and a decreased expression of genes involved in antiviral responses. Essentially, lonely people had a less effective immune response and more inflammation than non-lonely people.


conserved transcriptional response to adversity  逆境に対する保存性反応
transcriptional response  転写応答
adversity 逆境,不運. 不幸な出来事,災難.

For the current study, the team examined gene expression in leukocytes, cells of the immune system that are involved in protecting the body against bacteria and viruses.


As expected, the leukocytes of lonely humans and macaques showed the effects of CTRA--an increased expression of genes involved in inflammation and a decreased expression of genes involved in antiviral responses. But the study also revealed several important new pieces of information about loneliness' effect on the body.


First, the researchers found that loneliness predicted future CTRA gene expression measured a year or more later. Interestingly, CTRA gene expression also predicted loneliness measured a year or more later. Leukocyte gene expression and loneliness appear to have a reciprocal relationship, suggesting that each can help propagate the other over time. These results were specific to loneliness and could not be explained by depression, stress or social support.


reciprocal relationship 相互関係

Next, the team investigated the cellular processes linking social experience to CTRA gene expression in rhesus macaque monkeys at the California National Primate Research Center, which had been behaviorally classified as high in perceived social isolation. Like the lonely humans, the "lonely like" monkeys showed higher CTRA activity. They also showed higher levels of the fight-or-flight neurotransmitter, norepinephrine.


cellular processes細胞プロセス(代謝や分泌など細胞の機能が動く過程のこと)
social isolation. 社会的隔離
norepinephrine ノルアドレナリン

Previous research has found that norepinephrine can stimulate blood stem cells in bone marrow to make more of a particular kind of immune cell--an immature monocyte that shows high levels of inflammatory gene expression and low levels of antiviral gene expression. Both lonely humans and "lonely like" monkeys showed higher levels of monocytes in their blood.


immature monocyte 未成熟な単球

More detailed studies of the monkey white blood cells found that this difference stemmed from expansion of the pool of immature monocytes. In an additional study, monkeys repeatedly exposed to mildly stressful social conditions (unfamiliar cage-mates) also showed increases in immature monocyte levels. These analyses have finally identified one reason why CTRA gene expression is amplified in the white blood cell pool: increased output of immature monocytes.

サル白血球のより詳細な研究は、この違いが未成熟な単球の集積拡大から生じていることが分かりました。追加の研究では、軽度のストレスフルな社会条件(なじみのないケージ・仲間)に繰り返し暴露されたサルも未成熟な単球の増加を示した。これらの分析は、CTRA 遺伝子発現が白血球集積(未成熟な単球の産生増加)で増幅される理由のひとつを最終的に特定した.

white blood cells 白血球

Finally, the researchers determined that this monocyte-related CTRA shift had real consequences for health. In a monkey model of viral infection, the impaired antiviral gene expression in "lonely like" monkeys allowed simian immunodeficiency virus (the monkey version of HIV) to grow faster in both blood and brain.


simian immunodeficiency virus サル免疫不全ウイルス

Taken together, these findings support a mechanistic model in which loneliness results in fight-or-flight stress signaling, which increases the production of immature monocytes, leading to up-regulation of inflammatory genes and impaired anti-viral responses. The "danger signals" activated in the brain by loneliness ultimately affect the production of white blood cells. The resulting shift in monocyte output may both propagate loneliness and contribute to its associated health risks.


The team plans to continue research onhow loneliness leads to poor health outcomes and how these effects can be prevented in older adults



闘争・逃走反応(とうそう・とうそうはんのう、英語: fight-or-flight response)は、1929年にウォルター・B・キャノンによって初めて提唱された動物の恐怖への反応である[1][2][3]。闘争か逃走か反応、戦うか逃げるか反応ともいい、戦うか逃げるかすくむか反応(fight-or-flight-or-freeze response)、過剰反応(hyperarousal)、急性ストレス反応(acute stress response)とされることもある。

ノルアドレナリン 健康用語辞典より







ジョン・T・カシオポ (著) の本紹介



December 01, 2015


Tumor Angiogenesis as a Target for Dietary Cancer Prevention


Journal of Oncologyの記事より

1. Introduction


It is now well established that solid tumor growth is dependent upon angiogenesis, the growth of new blood vessels [5–10].. During early stages of tumorigenesis, the induction of angiogenesis by cancer cells is a critical event separating the preinvasive and dormant form of cancer from the invasive and metastatic phases of malignant growth.


solid tumor 固形腫瘍
malignant growth 悪性増殖
metastatic phase 転移相
preinvasive 前浸潤性の

Multiple studies have demonstrated that the degree of tumor vascularity correlates positively with disease stage, the likelihood of metastases, and cancer recurrence [11, 12]. Angiogenesis also plays a role in hematogenous malignancies, such as leukemia, lymphoma, and multiple myeloma, as well as in premalignant myelodysplastic syndromes [13–17]. In these pathologies, vascular endothelial cells sustain and promote malignant cell growth by secreting paracrine survival factors [18, 19].


tumor vascularity 腫瘍血管系
disease stage 病期
metastase 転移
hematogenous  血行性の

malignancies 悪性腫瘍
lymphoma リンパ腫
multiple myeloma 多発性骨髄腫
premalignant 前悪性
myelodysplastic syndromes 骨髄異形成症候群
vascular endothelial cells  血管内皮細胞
paracrine survival factors パラクリン生存因子

Antiangiogenic therapy has been validated as an effective cancer treatment strategy for a growing number of cancer types, including colorectal, renal, liver, lung, brain, pancreatic neuroendocrine tumors (NET), gastrointestinal stromal tumors (GIST), multiple myeloma, and myelodysplastic syndrome [20]. More than 120 novel antiangiogenic agents are in clinical, trials [20–22].Importantly, a growing body of preclinical, clinical and epidemiological data is demonstrating that angiogenesis inhibition can be applied for achieving cancer prevention [23, 24]. This paper presents the scientific and clinical evidence supporting antiangiogenesis as a rational strategy for the prevention of cancer, exploiting factors that are naturally present in dietary sources.


Antiangiogenic therapy 抗血管新生療法
colorectal, 大腸
pancreatic neuroendocrine tumors (NET) 膵神経内分泌腫瘍
gastrointestinal stromal tumors (GIST),消化管間質腫瘍
multiple myeloma 多発性骨髄腫
myelodysplastic syndrome  骨髄異形成症候群
antiangiogenic agents 血管新生阻害剤



傍分泌(ぼうぶんぴ・ぼうぶんぴつ、英語: Paracrine signalling、パラクリンシグナリング)とは、細胞間におけるシグナル伝達のひとつ。特定の細胞から分泌される物質が、血液中を通らず組織液などを介してその細胞の周辺で局所的な作用を発揮することである。パラクリンの「パラ」とは「近く」を意味しており、典型的なホルモンは特定の器官で産出された後、血流に乗り遠隔の標的器官で作用を発現するが、傍分泌ではシグナル分子が細胞外液を介して分泌する細胞の近くだけに拡散し、周辺の細胞に働きかける[1]。この傍分泌にかかわるタンパク質はパラクリン因子(または単にパラクリン)と呼ばれ、発生や損傷部位の細胞増殖や腫瘍などにおいて重要な役割を担っている。





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