Stress and telomere shortening: Insights from cellular mechanisms.
Stress and telomere shortening: Insights from cellular mechanisms.
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DOI：
10.1016/j.arr.2021.101507
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发表时间：
2022-01
影响因子：
13.1
通讯作者：
Epel E
中科院分区：
文献类型：
--
作者：
Lin J;Epel E
端粒较短会增加患退行性疾病的风险。慢性心理应激可通过多种途径导致疾病，从体外研究到人类纵向研究都指出，应激诱导的端粒损伤是一条重要途径。然而，目前还没有一个全面的模型来描述应激生理学和神经内分泌通路的变化如何导致端粒生物学的变化。端粒过短或端粒结构的崩溃是由于端粒结合蛋白复合体的移位引起的，可引起DNA损伤反应，导致衰老或细胞凋亡。在这篇叙述性综述中，我们总结了糖皮质激素、活性氧(ROS)和线粒体，以及炎症在调节心理应激和端粒维持之间的关系中所起的关键作用。我们强调，在正反馈循环中，这些调解人是相互联系和相互加强的。端粒长度在整个生命周期中还没有被研究过，但出生时的初始设定点似乎是最有影响力的点，因为它决定了生命轨迹，并受到压力的影响。我们描述了两种类型的代际应激对端粒的影响--胎儿发育过程中的产前应激对端粒的影响，以及“端型传递”--从父母的生殖系直接继承的短端粒的传递。很明显，最初认为端粒长度是有丝分裂时钟的简单化观点，已经演变成一幅复杂得多的图景，既有跨代影响的端粒，也有相互连接的分子和细胞路径和网络，作为衰老的标志，端粒维持是与线粒体相互作用的关键角色。进一步的机制研究将有助于更好地理解从细胞到人类寿命的衰老，并可能导致抗衰老干预措施。
Short telomeres confer risk of degenerative diseases. Chronic psychological stress can lead to disease through many pathways, and research from in vitro studies to human longitudinal studies has pointed to stress-induced telomere damage as an important pathway. However, there has not been a comprehensive model to describe how changes in stress physiology and neuroendocrine pathways can lead to changes in telomere biology. Critically short telomeres or the collapse of the telomere structure caused by displacement of telomere binding protein complex shelterin elicit a DNA damage response and lead to senescence or apoptosis. In this narrative review, we summarize the key roles glucocorticoids, reactive oxygen species (ROS) and mitochondria, and inflammation play in mediating the relationship between psychological stress and telomere maintenance. We emphasis that these mediators are interconnected and reinforce each other in positive feedback loops. Telomere length has not been studied across the lifespan yet, but the initial setting point at birth appears to be the most influential point, as it sets the lifetime trajectory, and is influenced by stress. We describe two types of intergenerational stress effects on telomeres – prenatal stress effects on telomeres during fetal development, and ‘telotype transmission”–the directly inherited transmission of short telomeres from parental germline. It is clear that the initial simplistic view of telomere length as a mitotic clock has evolved into a far more complex picture of both transgenerational telomere influences, and of interconnected molecular and cellular pathways and networks, as hallmarks of aging where telomere maintenance is a key player interacting with mitochondria. Further mechanistic investigations testing this comprehensive model of stress mediators shaping telomere biology and the telomere-mitochondrial nexus will lead to better understanding from cell to human lifespan aging, and could lead to anti-aging interventions.
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DOI：
10.1016/j.mrfmmm.2011.04.003
发表时间：
2012-02-01
影响因子：
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作者：
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通讯作者：
Lansdorp, Peter M.
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作者：
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影响因子：
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