Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells.
Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells.
复制标题
DOI：
10.18632/aging.100717
复制
发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Zhavoronkov A
中科院分区：
文献类型：
--
作者：
Aliper AM;Csoka AB;Buzdin A;Jetka T;Roumiantsev S;Moskalev A;Zhavoronkov A
在过去的几十年里，随着对早衰综合征的分析，在理解人类衰老的分子基础方面的研究取得了显著进展。孕激素是层蛋白A的一种改变形式，已被确认为Hutchinson-Gilford Progeria综合征(HGPS)过早衰老的原因，并可能是正常衰老的一个促成因素。然而，HGPS究竟是在细胞和机体水平上重现了正常的衰老过程，还是只是模仿了衰老的表型，这一问题仍然存在广泛的争论。在目前的研究中，我们分析了可公开获得的培养中经历细胞老化的成纤维细胞的微阵列数据集，以及来自年轻、中年和老年个体的成纤维细胞，以及患有HGP的患者。利用GeroScope通路分析和药物发现平台，我们分析了65条主要细胞信号通路的激活状态。我们的分析表明，来自HGPS年轻患者的细胞中的信号通路激活状态与来自正常中老年人的细胞非常相似。这清楚地表明，HGPS可能真的代表着加速衰老，而不仅仅是一个假象。我们的数据还指出了可以有针对性地开发针对HGP和正常衰老的药物和药物组合的潜在途径。
For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging.
登录
查看更多内容
DOI：
10.18632/aging.100521
发表时间：
2012-12
期刊：
Aging
影响因子：
--
作者：
Halicka HD;Zhao H;Li J;Lee YS;Hsieh TC;Wu JM;Darzynkiewicz Z
通讯作者：
Darzynkiewicz Z
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.18632/aging.100455
发表时间：
2012-05
期刊：
Aging
影响因子：
--
作者：
Berstein LM
通讯作者：
Berstein LM
DOI：
10.18632/aging.100383
发表时间：
2011-09
期刊：
Aging
影响因子：
--
作者：
Dreesen O;Stewart CL
通讯作者：
Stewart CL
影响因子：
--
作者：
Borisov NM;Terekhanova NV;Aliper AM;Venkova LS;Smirnov PY;Roumiantsev S;Korzinkin MB;Zhavoronkov AA;Buzdin AA
通讯作者：
Buzdin AA