3篇论文证实!“压力大”缩短寿命、加速癌细胞生长……
2018/06/03
众所周知,压力太大有害健康。继去年发表在Science子刊上的一篇论文称,压力可激活癌细胞后,近日又有两项新研究证实了“压力的危害”,包括缩短寿命、改变身体器官。


Credit: Illustration by Gosia Herba

论文一:小鼠研究证实,社会压力与寿命缩短有关

5月28日,发表在Aging Cell杂志上题为“Social stress shortens lifespan in mice”的研究中,来自明尼苏达大学医学院的科学家们证明,持久的社会压力会导致小鼠寿命缩短,并增加患心血管疾病的风险。

据称,这是首个利用啮齿动物模型调查和剖析慢性压力对寿命、细胞衰老机制以及与衰老相关疾病(如动脉粥样硬化)的影响的研究。

具体来说,在这项研究中,科学家们通过让雄性小鼠非常靠近另一只小鼠,并量化攻击和顺从行为标志物(aggression and submissive behavioral markers)来模拟心理社会压力。

除了寿命的缩短,研究人员还观察到小鼠更早的出现了器官病变和肿瘤,且衰老细胞的标志物也增加了。此外,他们还观察到了早期动脉粥样硬化的自发发生。

领导该研究的Alessandro Bartolomucci博士说:“尽管这一现象先前已经为大家所知,且在许多关于慢性压力和社会经济地位低下对人类健康影响的、具有里程碑意义的研究中得到了证实,但由于这些发现从未在任何动物模型中被重复,因此,压力与衰老和生存之间的关联机制仍不清楚。而这正是我们研究的切入点。”

展望未来,Bartolomucci博士希望,利用这一工作以及今后的研究可以更好的理解压力诱导疾病背后的机制。他们最终的目标是,发现能够让人活得更久、更健康的途径。

论文二:婴儿期的压力显著改变了身体器官

2月6日,发表在Frontiers in Molecular Neuroscience上题为“Molecular Characterization of GABA-A Receptor Subunit Diversity within Major Peripheral Organs and Their Plasticity in Response to Early Life Psychosocial Stress”的研究中,科学家们找到了首个证据,证明婴儿时期的情绪压力对身体有重大且深远的影响,甚至可能在以后的生活中导致疾病。


Researchers Dr Mohsen Seifi, left, and Adina Gibbard, who is now studying for her PhD(图片来源:University of Portsmouth)

领导该研究的Mohsen Seifi博士说:“长期以来人们已经知道,童年的逆境(如忽视或虐待)会使人在以后的生活中更易患一系列的疾病,包括精神疾病(如焦虑)、心血管疾病或代谢紊乱。然而,这种情绪压力是如何影响身体内不同器官的正常功能的依然难以捉摸,这也阻碍了有效药物的开发。”


Microscopic image of the GABAA receptor in the mouse intestine(图片来源:University of Portsmouth)

这项研究发现,婴儿时期的心理压力会显著改变一类重要蛋白质——GABAA受体的数量,而这反过来可能会改变心脏、肺、肾脏和膀胱的工作。

事实上,先前已有研究证实,GABAA受体数量的改变会导致某些脑部疾病,但该研究中,英国朴次茅斯大学的科学家们首次证实,压力能够改变其他器官中GABAA受体的表达。


The GABAA receptor CREDIT: Wikipedia

参与该研究的Jerome Swinny博士说:“我们先前知道,GABAA受体能够控制大脑活动,且是现代医学中用于治疗脑部疾病(如癫痫、焦虑)的多种药物的重要靶点。但在该研究中,我们惊讶地发现,这些蛋白质也会在大脑之外如此广泛地表达。压力诱导的GABAA受体数量的显著变化是耐人寻味的。我们认为,这种变化将改变器官的功能,从而导致器官疾病。”

“持续的压力对我们的生存是有害的。由于婴儿的神经系统还不够成熟,因此还不足以应对‘长期接触调节压力反应的化学物质’。这种经历(长期压力大)往往会使他们更容易改变身心的正常发育。”Seifi博士解释道。

作者们认为,该研究成果带来了一种希望,即靶向这些受体的药物或许能够治疗包括高血压、糖尿病等在内的多种疾病。


图片来源:Science Translational Medicine(DOI: 10.1126/scitranslmed.aao4307)

论文三:压力可加速癌细胞生长

2017年11月8日,发表在Science Translational Medicine上题为“Stress hormones promote EGFR inhibitor resistance in NSCLC: Implications for combinations with β-blockers”的研究中,来自MD安德森癌症中心的科学家们发现,压力会导致肺癌耐药性的发生,加速癌细胞的生长。而一类缓解压力的常规药物能够起到增强抗癌药疗效的作用。

“在你身体里感知压力的受体,也同样存在于癌细胞表面,并且能‘激活’这些癌细胞。” 该研究的第一作者Monique Nilsson博士说。(点击《Science子刊:压力可激活癌细胞,请轻松生活》查看关于该研究的详细报道。)


图片来源:16sucai

小结

压力大的危害已被多篇论文证实。愿大家在生活中能够调节好自己的情绪,让日子变得“轻松”些!

责编:风铃

参考资料:

Study demonstrates link between social stress and shortened lifespan in mice

Stress in infancy 'dramatically alters' body's organs

Science子刊:压力可激活癌细胞,请轻松生活

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  • Social stress shortens lifespan in mice

    Stress and low socioeconomic status in humans confer increased vulnerability to morbidity and mortality. However, this association is not mechanistically understood nor has its causation been explored in animal models thus far. Recently, cellular senescence has been suggested as a potential mechanism linking lifelong stress to age‐related diseases and shorter life expectancy in humans. Here, we established a causal role for lifelong social stress on shortening lifespan and increasing the risk of cardiovascular disease in mice. Specifically, we developed a lifelong chronic psychosocial stress model in which male mouse aggressive behavior is used to study the impact of negative social confrontations on healthspan and lifespan. C57BL/6J mice identified through unbiased cluster analysis for receiving high while exhibiting low aggression, or identified as subordinate based on an ethologic criterion, had lower median and maximal lifespan, and developed earlier onset of several organ pathologies in the presence of a cellular senescence signature. Critically, subordinate mice developed spontaneous early‐stage atherosclerotic lesions of the aortic sinuses characterized by significant immune cells infiltration and sporadic rupture and calcification, none of which was found in dominant subjects. In conclusion, we present here the first rodent model to study and mechanistically dissect the impact of chronic stress on lifespan and disease of aging. These data highlight a conserved role for social stress and low social status on shortening lifespan and increasing the risk of cardiovascular disease in mammals and identify a potential mechanistic link for this complex phenomenon.

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  • Molecular Characterization of GABA-A Receptor Subunit Diversity within Major Peripheral Organs and Their Plasticity in Response to Early Life Psychosocial Stress

    Gamma aminobutyric acid (GABA) subtype A receptors (GABAARs) are integral membrane ion channels composed of five individual proteins or subunits. Up to 19 different GABAAR subunits (α1–6, β1–3, γ1–3, δ, ε, θ, π, and ρ1–3) have been identified, resulting in anatomically, physiologically, and pharmacologically distinct multiple receptor subtypes, and therefore GABA-mediated inhibition, across the central nervous system (CNS). Additionally, GABAAR-modulating drugs are important tools in clinical medicine, although their use is limited by adverse effects. While significant advances have been made in terms of characterizing the GABAAR system within the brain, relatively less is known about the molecular phenotypes within the peripheral nervous system of major organ systems. This represents a potentially missed therapeutic opportunity in terms of utilizing or repurposing clinically available GABAAR drugs, as well as promising research compounds discarded due to their poor CNS penetrance, for the treatment of peripheral disorders. In addition, a broader understanding of the peripheral GABAAR subtype repertoires will contribute to the design of therapies which minimize peripheral side-effects when treating CNS disorders. We have recently provided a high resolution molecular and function characterization of the GABAARs within the enteric nervous system of the mouse colon. In this study, the aim was to determine the constituent GABAAR subunit expression profiles of the mouse bladder, heart, liver, kidney, lung, and stomach, using reverse transcription polymerase chain reaction and western blotting with brain as control. The data indicate that while some subunits are expressed widely across various organs (α3–5), others are restricted to individual organs (γ2, only stomach). Furthermore, we demonstrate complex organ-specific developmental expression plasticity of the transporters which determine the chloride gradient within cells, and therefore whether GABAAR activation has a depolarizing or hyperpolarizing effect. Finally, we demonstrate that prior exposure to early life psychosocial stress induces significant changes in peripheral GABAAR subunit expression and chloride transporters, in an organ- and subunit-specific manner. Collectively, the data demonstrate the molecular diversity of the peripheral GABAAR system and how this changes dynamically in response to life experience. This provides a molecular platform for functional analyses of the GABA–GABAAR system in health, and in diseases affecting various peripheral organs.

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