Accelerated aging syndromes, are they relevant to normal human aging?
Accelerated aging syndromes, are they relevant to normal human aging?
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DOI：
10.18632/aging.100383
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发表时间：
2011-09
期刊：
影响因子：
--
通讯作者：
Stewart CL
中科院分区：
文献类型：
--
作者：
Dreesen O;Stewart CL
Hutchinson-Gilford早衰症（HGPS）和Werner综合征是临床上类似加速老化的某些方面的疾病。HGPS是由LMNA基因突变引起的，导致翻译后加工缺陷，引发儿童早衰症。Werner综合征，由WRN解旋酶基因突变引起，导致年轻人过早衰老。这些疾病背后的分子机制是什么？这些疾病的哪些方面与人类生理衰老相似？我们所知道的大部分源于对患者来源的成纤维细胞的研究，这两种突变导致DNA损伤增加，主要是在端粒。然而，体内维尔纳氏病患者会发生动脉硬化等病理。在HGPS患者中，包括来自HGPS患者的iPS衍生细胞，以及一些早衰症的小鼠模型，血管平滑肌（VSM）似乎是受影响最严重的组织之一。与DNA损伤相关的核纤层蛋白加工缺陷存在于老年人的VSM中，表明加工缺陷可能是正常衰老的一个因素。持续的DNA损伤，特别是在端粒，是否是这些病理的根本原因仍有待确定，因为不是所有的早老样Lmna突变都会导致DNA损伤和基因组不稳定。
Hutchinson-Gilford Progeria (HGPS) and Werner syndromes are diseases that clinically resemble some aspects of accelerated aging. HGPS is caused by mutations in theLMNA gene resulting in post-translational processing defects that trigger Progeria in children. Werner syndrome, arising from mutations in the WRN helicase gene, causes premature aging in young adults. What are the molecular mechanism(s) underlying these disorders and what aspects of the diseases resemble physiological human aging? Much of what we know stems from the study of patient derived fibroblasts with both mutations resulting in increased DNA damage, primarily at telomeres. However, in vivo patients with Werner's develop arteriosclerosis, among other pathologies. In HGPS patients, including iPS derived cells from HGPS patients, as well as some mouse models for Progeria, vascular smooth muscle (VSM) appears to be among the most severely affected tissues. Defective Lamin processing, associated with DNA damage, is present in VSM from old individuals, indicating processing defects may be a factor in normal aging. Whether persistent DNA damage, particularly at telomeres, is the root cause for these pathologies remains to be established, since not all progeroid Lmna mutations result in DNA damage and genome instability.
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DOI：
10.1126/science.1170633
发表时间：
2009-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
de Lange T
通讯作者：
de Lange T
影响因子：
82.9
作者：
Liu, BH;Wang, JM;Zhou, ZJ
通讯作者：
Zhou, ZJ
DOI：
10.1073/pnas.192460799
发表时间：
2002-10-01
影响因子：
11.1
作者：
Bergo, MO;Gavino, B;Young, SG
通讯作者：
Young, SG
影响因子：
11.8
作者：
Hernandez, Lidia;Roux, Kyle J.;Stewart, Colin L.
通讯作者：
Stewart, Colin L.
DOI：
10.1073/pnas.0609410104
发表时间：
2007-02-13
影响因子：
11.1
作者：
Crabbe, Laure;Jauch, Anna;Karlseder, Jan
通讯作者：
Karlseder, Jan