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与人类外周血单个核细胞中氧化损伤DNA相关的年龄和代谢风险因素。

Age and metabolic risk factors associated with oxidatively damaged DNA in human peripheral blood mononuclear cells.

作者信息

Løhr Mille, Jensen Annie, Eriksen Louise, Grønbæk Morten, Loft Steffen, Møller Peter

机构信息

Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark.

National Institute of Public Health, University of Southern Denmark, Odense, Denmark.

出版信息

Oncotarget. 2015 Feb 20;6(5):2641-53. doi: 10.18632/oncotarget.3202.

Abstract

Aging is associated with oxidative stress-generated damage to DNA and this could be related to metabolic disturbances. This study investigated the association between levels of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs) and metabolic risk factors in 1,019 subjects, aged 18-93 years. DNA damage was analyzed as strand breaks by the comet assay and levels of formamidopyrimidine (FPG-) and human 8-oxoguanine DNA glycosylase 1 (hOGG1)-sensitive sites There was an association between age and levels of FPG-sensitive sites for women, but not for men. The same tendency was observed for the level of hOGG1-sensitive sites, whereas there was no association with the level of strand breaks. The effect of age on oxidatively damaged DNA in women disappeared in multivariate models, which showed robust positive associations between DNA damage and plasma levels of triglycerides, cholesterol and glycosylated hemoglobin (HbA1c). In the group of men, there were significant positive associations between alcohol intake, HbA1c and FPG-sensitive sites in multivariate analysis. The levels of metabolic risk factors were positively associated with age, yet only few subjects fulfilled all metabolic syndrome criteria. In summary, positive associations between age and levels of oxidatively damaged DNA appeared mediated by age-related increases in metabolic risk factors.

摘要

衰老与氧化应激导致的DNA损伤有关,这可能与代谢紊乱有关。本研究调查了1019名年龄在18至93岁之间的受试者外周血单个核细胞(PBMC)中氧化损伤DNA水平与代谢风险因素之间的关联。通过彗星试验将DNA损伤分析为链断裂,并分析甲酰胺嘧啶(FPG-)和人8-氧代鸟嘌呤DNA糖基化酶1(hOGG1)敏感位点的水平。女性的年龄与FPG敏感位点水平之间存在关联,而男性则不存在。hOGG1敏感位点水平也观察到相同趋势,而与链断裂水平无关。在多变量模型中,年龄对女性氧化损伤DNA的影响消失,该模型显示DNA损伤与血浆甘油三酯、胆固醇和糖化血红蛋白(HbA1c)水平之间存在强烈的正相关。在男性组中,多变量分析显示酒精摄入量、HbA1c与FPG敏感位点之间存在显著的正相关。代谢风险因素水平与年龄呈正相关,但只有少数受试者符合所有代谢综合征标准。总之,年龄与氧化损伤DNA水平之间的正相关似乎是由与年龄相关的代谢风险因素增加介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a3/4413607/05d4201ac28c/oncotarget-06-2641-g001.jpg

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