Progeria of stem cells: Stem cell exhaustion in Hutchinson-Gilford progeria syndrome
Progeria of stem cells: Stem cell exhaustion in Hutchinson-Gilford progeria syndrome
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DOI：
10.1093/gerona/62.1.3
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发表时间：
2007-01-01
影响因子：
5.1
通讯作者：
Brooks-Wilson, Angela
中科院分区：
文献类型：
--
作者：
Halaschek-Wiener, Julius;Brooks-Wilson, Angela
哈钦森-吉尔福德早衰综合症 (HGPS) 是一种罕见的致命遗传性疾病，其特点是节段性加速衰老。与 HGPS 相关的主要因果突变会触发核纤层蛋白 A 基因的异常信使 RNA 剪接，从而导致核结构的变化。迄今为止，已经提出了两种模型来解释核纤层蛋白 A 基因的突变如何导致 HGPS、结构脆性和基因表达改变。我们赞成将 HGPS 与干细胞驱动的组织再生联系起来的兼容模型。在该模型中，核纤层蛋白 A 缺陷细胞的核脆性增加了细胞凋亡，达到耗尽组织干细胞驱动再生能力的水平。细胞死亡或再生潜力或两者的组织特异性差异导致 HGPS 中看到的组织特异性节段老化模式。我们提出，HGPS 中存在或不存在的与衰老相关的条件模式可以提供对导致正常衰老的遗传和环境因素的深入了解。
Hutchinson-Gilford progeria syndrome (HGPS) is a rare, fatal genetic disorder that is characterized by segmental accelerated aging. The major causal mutation associated with HGPS triggers abnormal messenger RNA splicing of the lamin A gene leading to changes in the nuclear architecture. To date, two models have been proposed to explain how mutations in the lamin A gene could lead to HGPS, structural fragility and altered gene expression. We favor a compatible model that links HGPS to stem cell-driven tissue regeneration. In this model, nuclear fragility of lamin A-deficient cells increases apoptotic cell death to levels that exhaust tissues' ability for stem cell-driven regeneration. Tissue-specific differences in cell death or regenerative potential, or both, result in the tissue-specific segmental aging pattern seen in HGPS. We propose that the pattern of aging-related conditions present or absent in HGPS can provide insight into the genetic and environmental factors that contribute to normal aging.