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巨细胞病毒与 Whitehall II 队列中端粒酶活性降低有关。

Cytomegalovirus is associated with reduced telomerase activity in the Whitehall II cohort.

机构信息

Epidemiology and Biostatistics, Hunter College, CUNY School of Public Health, 2180 Third Avenue, New York, NY 10035, USA.

出版信息

Exp Gerontol. 2013 Apr;48(4):385-90. doi: 10.1016/j.exger.2013.01.016. Epub 2013 Feb 9.

Abstract

Telomere length and telomerase activity have received increased attention as markers of cellular aging, but the determinants of inter-individual variation in these markers are incompletely understood. Cytomegalovirus (CMV) infection may be particularly important for telomere and telomerase dynamics due to its dramatic impact on peripheral blood lymphocyte composition, i.e., increasing the number and proportions of highly differentiated T cells that are characterized by shorter telomere length (TL) and lowered telomerase activity (TA). However, the possible relationship between CMV infection and leukocyte TL and TA has not been well-examined in vivo. This study examined the associations of CMV seropositivity and CMV IgG antibodies with leukocyte (TL) and (TA) in a sample of 434 healthy individuals (ages 53-76) from the Whitehall II cohort. Positive CMV serostatus was significantly associated with lower TA among women, and higher CMV IgG antibody levels were associated with lower TA in the overall sample. However, neither CMV seropositivity nor CMV IgG antibody levels (reflecting subclinical reactivation) among the seropositive were significantly associated with TL. These associations were robust to adjustment for age, employment grade, BMI, and smoking status. The results demonstrate that CMV seropositivity and subclinical reactivation predict lower TA. Future longitudinal studies should test whether the association of CMV with lower TA contributes to accelerated telomere shortening over time.

摘要

端粒长度和端粒酶活性作为细胞衰老的标志物受到了越来越多的关注,但这些标志物个体间差异的决定因素尚未完全阐明。巨细胞病毒(CMV)感染可能对端粒和端粒酶动态特别重要,因为它对周围血淋巴细胞组成产生了巨大影响,即增加了具有较短端粒长度(TL)和降低端粒酶活性(TA)的高度分化 T 细胞的数量和比例。然而,CMV 感染与白细胞 TL 和 TA 之间的可能关系在体内尚未得到很好的研究。本研究在 Whitehall II 队列的 434 名健康个体(年龄 53-76 岁)样本中,研究了 CMV 血清阳性和 CMV IgG 抗体与白细胞(TL)和(TA)之间的关联。CMV 血清阳性与女性 TA 降低显著相关,总样本中 CMV IgG 抗体水平较高与 TA 降低相关。然而,CMV 血清阳性者的 CMV 血清阳性率或 CMV IgG 抗体水平(反映亚临床再激活)均与 TL 无显著关联。这些关联在调整年龄、就业等级、BMI 和吸烟状况后仍然稳健。研究结果表明,CMV 血清阳性和亚临床再激活可预测 TA 降低。未来的纵向研究应检验 CMV 与较低 TA 的关联是否会导致随着时间的推移端粒缩短加速。

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本文引用的文献

1
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Nat Rev Genet. 2012 Oct;13(10):693-704. doi: 10.1038/nrg3246. Epub 2012 Sep 11.
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Curr Opin Immunol. 2012 Aug;24(4):470-5. doi: 10.1016/j.coi.2012.05.001. Epub 2012 May 22.
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The impact of CMV infection on survival in older humans.巨细胞病毒感染对老年人存活的影响。
Curr Opin Immunol. 2012 Aug;24(4):507-11. doi: 10.1016/j.coi.2012.04.002. Epub 2012 Apr 27.
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Human telomerase expression regulation.人类端粒酶表达调控。
Biochem Cell Biol. 2011 Aug;89(4):359-76. doi: 10.1139/o11-037. Epub 2011 Jul 26.
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Telomeres in cancer and ageing.端粒与癌症和衰老。
Philos Trans R Soc Lond B Biol Sci. 2011 Jan 12;366(1561):76-84. doi: 10.1098/rstb.2010.0291.

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