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逆转录病毒基因表达作为衰老的一种可能生物标志物。

Retroviral gene expression as a possible biomarker of aging.

作者信息

Wada Y, Tsukada M, Kamiyama S, Koizumi A

机构信息

Akita Prefectural Oodate Health Center, Japan.

出版信息

Int Arch Occup Environ Health. 1993;65(1 Suppl):S235-9. doi: 10.1007/BF00381349.

DOI:10.1007/BF00381349
PMID:7691759
Abstract

We examined effects of aging on endogenous retrovirus gene expression of mouse lymphocytes with a hypothesis that it may be a useful biomarker of aging. Mice have endogenous murine leukemia viruses (MuLVs) in their chromosomes. We detected the gene expression of long terminal repeats (LTRs) of MuLVs. Brains, livers and spleens were taken from young (3 months old) and old (27 months old) male C57BL/6 mice. In addition to these control (C) mice, we also determined gene expression in dietary restricted (DR) mice, in which rates of aging are known to be slowed. RNA was extracted from the tissues and converted into cDNA. The MuLV-LTR portion of cDNA was amplified by polymerase chain reaction (PCR). The PCR products were analyzed by agarose gel electrophoresis. Gene expressions of young mice were found to be tissue-specific. Expressed LTRs from brains, livers and spleens were that of 370 base-pairs (bp), those of 370 and 620 bp, and those of 370, 400 and 620 bp, respectively. Old mice of C group, however, decreased tissue specificity: expressed LTRs became those of 370-400 bp in any tissues. In contrast the tissue specific gene expression was conserved in old DR mice which had to get prolonged life span and decreased lymphoma incidence. Thereby, gene expression of endogenous retroviruses appears to change during aging and to be modifiable by life-prolonging DR. It may be therefore used as a biomarker of aging in mice. Humans are known to have similar gene elements like MuLV. The present findings demonstrate a possibility of application of endogenous gene expressions to the epidemiology of aging.

摘要

我们研究了衰老对小鼠淋巴细胞内源性逆转录病毒基因表达的影响,提出这可能是一种有用的衰老生物标志物的假设。小鼠染色体中存在内源性鼠白血病病毒(MuLVs)。我们检测了MuLVs长末端重复序列(LTRs)的基因表达。从年轻(3个月大)和年老(27个月大)的雄性C57BL/6小鼠身上获取脑、肝和脾。除了这些对照(C)小鼠外,我们还测定了饮食限制(DR)小鼠的基因表达,已知这些小鼠的衰老速度会减慢。从组织中提取RNA并转化为cDNA。通过聚合酶链反应(PCR)扩增cDNA的MuLV-LTR部分。PCR产物通过琼脂糖凝胶电泳进行分析。发现年轻小鼠的基因表达具有组织特异性。从脑、肝和脾中表达的LTRs分别为370个碱基对(bp)、370和620 bp以及370、400和620 bp。然而,C组的老年小鼠组织特异性降低:在任何组织中表达的LTRs都变为370 - 400 bp。相比之下,在寿命延长且淋巴瘤发病率降低的老年DR小鼠中,组织特异性基因表达得以保留。因此,内源性逆转录病毒的基因表达似乎在衰老过程中发生变化,并且可以通过延长寿命的饮食限制来改变。所以,它可能被用作小鼠衰老的生物标志物。已知人类具有与MuLV类似的基因元件。目前的研究结果表明内源性基因表达应用于衰老流行病学的可能性。

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本文引用的文献

1
The four classes of endogenous murine leukemia virus: structural relationships and potential for recombination.内源性鼠白血病病毒的四类:结构关系及重组潜力
J Virol. 1987 Sep;61(9):2659-69. doi: 10.1128/JVI.61.9.2659-2669.1987.
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Studies on emerging radiation leukemia virus variants in C57BL/Ka mice.C57BL/Ka小鼠中新兴辐射白血病病毒变体的研究。
J Virol. 1986 Apr;58(1):96-106. doi: 10.1128/JVI.58.1.96-106.1986.
3
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.采用酸性硫氰酸胍-苯酚-氯仿萃取法一步分离RNA的方法。
Anal Biochem. 1987 Apr;162(1):156-9. doi: 10.1006/abio.1987.9999.
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Biomarkers of aging: do we know what to look for?衰老的生物标志物:我们知道该寻找什么吗?
J Gerontol. 1990 Nov;45(6):B183-6. doi: 10.1093/geronj/45.6.b183.
5
Effects of energy restriction on mouse mammary tumor virus mRNA levels in mammary glands and uterus and on uterine endometrial hyperplasia and pituitary histology in C3H/SHN F1 mice.能量限制对C3H/SHN F1小鼠乳腺和子宫中鼠乳腺肿瘤病毒mRNA水平以及子宫内膜增生和垂体组织学的影响。
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