Age-associated increase in heterochromatic marks in murine and primate tissues.
Age-associated increase in heterochromatic marks in murine and primate tissues.
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DOI：
10.1111/j.1474-9726.2010.00666.x
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发表时间：
2011-04
期刊：
影响因子：
7.8
通讯作者：
Sedivy JM
中科院分区：
文献类型：
--
作者：
Kreiling JA;Tamamori-Adachi M;Sexton AN;Jeyapalan JC;Munoz-Najar U;Peterson AL;Manivannan J;Rogers ES;Pchelintsev NA;Adams PD;Sedivy JM
染色质是高度动态的，并且在许多生理条件下受到广泛的重塑。在高等生物（如哺乳动物）中，在衰老过程中发生的染色质变化的记录和理解很少。我们开发了一种免疫荧光法，以定量检测，在单细胞水平上，染色质相关蛋白的核含量的变化。我们发现在培养的复制衰老过程中，人类成纤维细胞中异染色质相关蛋白组蛋白宏H2A（mH2A）和异染色质蛋白1 β（HP 1 β）的水平增加，并且第一次在小鼠和灵长类动物的几种组织中发现这些异染色质标记的年龄相关增加。小鼠肺的特点是双相mH2A表达直方图在两个年龄，并在老年平均染色强度增加。在小鼠肝脏中，我们观察到年龄相关的mH2A的区域的着丝粒周围异染色质的本地化。在骨骼肌中，我们发现两个群体的细胞与低或高mH2A水平。这种表达模式在小鼠和狒狒中是相似的，并且在老年动物中具有高mH2A水平的细胞核的比例明显增加。显示异染色质化增加证据的细胞的频率太高，以至于不能容易地通过复制或癌基因诱导的细胞衰老来解释，并且在通常认为不易衰老的终末分化的有丝分裂后组织中显著发现。我们的研究结果区分了哺乳动物组织单个细胞中的特定染色质状态，并为进一步研究衰老过程中发生的渐进性表观遗传变化提供了基础。
Chromatin is highly dynamic and subject to extensive remodeling under many physiological conditions. Changes in chromatin that occur during the aging process are poorly documented and understood in higher organisms, such as mammals. We developed an immunofluorescence assay to quantitatively detect, at the single cell level, changes in the nuclear content of chromatin-associated proteins. We find increased levels of the heterochromatin-associated proteins histone macro H2A (mH2A) and heterochromatin protein 1 beta (HP1β) in human fibroblasts during replicative senescence in culture, and for the first time, an age-associated increase in these heterochromatin marks in several tissues of mice and primates. Mouse lung was characterized by monophasic mH2A expression histograms at both ages, and an increase in mean staining intensity at old age. In the mouse liver we observed increased age-associated localization of mH2A to regions of pericentromeric heterochromatin. In skeletal muscle we found two populations of cells with either low or high mH2A levels. This pattern of expression was similar in mouse and baboon, and showed a clear increase in the proportion of nuclei with high mH2A levels in older animals. The frequencies of cells displaying evidence of increased heterochromatinization are too high to be readily accounted for by replicative or oncogene-induced cellular senescence, and are prominently found in terminally differentiated, post mitotic tissues that are not conventionally thought to be susceptible to senescence. Our findings distinguish specific chromatin states in individual cells of mammalian tissues, and provide a foundation to further investigate the progressive epigenetic changes that occur during aging.
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影响因子：
64.8
作者：
Bartkova, Jirina;Rezaei, Nousin;Gorgoulis, Vassilis G.
通讯作者：
Gorgoulis, Vassilis G.
影响因子：
64.8
作者：
Di Micco, Raffaella;Fumagalli, Marzia;di Fagagna, Fabrizio d'Adda
通讯作者：
di Fagagna, Fabrizio d'Adda
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
5.3
作者：
Changolkar, Lakshmi N.;Singh, Geetika;Pehrson, John R.
通讯作者：
Pehrson, John R.