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普通狨猴衰老模型中血浆硫醇氧化还原电位的表征

Characterization of plasma thiol redox potential in a common marmoset model of aging.

作者信息

Roede James R, Uppal Karan, Liang Yongliang, Promislow Daniel E L, Wachtman Lynn M, Jones Dean P

机构信息

Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, GA, USA.

出版信息

Redox Biol. 2013 Jul 18;1(1):387-93. doi: 10.1016/j.redox.2013.06.003. eCollection 2013.

Abstract

Due to its short lifespan, ease of use and age-related pathologies that mirror those observed in humans, the common marmoset (Callithrix jacchus) is poised to become a standard nonhuman primate model of aging. Blood and extracellular fluid possess two major thiol-dependent redox nodes involving cysteine (Cys), cystine (CySS), glutathione (GSH) and glutathione disulfide (GSSG). Alteration in these plasma redox nodes significantly affects cellular physiology, and oxidation of the plasma Cys/CySS redox potential (E hCySS) is associated with aging and disease risk in humans. The purpose of this study was to determine age-related changes in plasma redox metabolites and corresponding redox potentials (E h) to further validate the marmoset as a nonhuman primate model of aging. We measured plasma thiol redox states in marmosets and used existing human data with multivariate adaptive regression splines (MARS) to model the relationships between age and redox metabolites. A classification accuracy of 70.2% and an AUC of 0.703 were achieved using the MARS model built from the marmoset redox data to classify the human samples as young or old. These results show that common marmosets provide a useful model for thiol redox biology of aging.

摘要

由于普通狨猴(Callithrix jacchus)寿命短、易于使用且具有与人类相似的与年龄相关的病理特征,它有望成为衰老研究的标准非人类灵长类动物模型。血液和细胞外液具有两个主要的依赖硫醇的氧化还原节点,涉及半胱氨酸(Cys)、胱氨酸(CySS)、谷胱甘肽(GSH)和谷胱甘肽二硫化物(GSSG)。这些血浆氧化还原节点的改变会显著影响细胞生理,血浆Cys/CySS氧化还原电位(E hCySS)的氧化与人类的衰老和疾病风险相关。本研究的目的是确定血浆氧化还原代谢物与相应氧化还原电位(E h)的年龄相关变化,以进一步验证狨猴作为衰老的非人类灵长类动物模型。我们测量了狨猴的血浆硫醇氧化还原状态,并使用现有的人类数据和多元自适应回归样条(MARS)来模拟年龄与氧化还原代谢物之间的关系。使用从狨猴氧化还原数据构建的MARS模型将人类样本分类为年轻或年老,分类准确率达到70.2%,曲线下面积(AUC)为0.703。这些结果表明,普通狨猴为衰老的硫醇氧化还原生物学提供了一个有用的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97bf/3757708/a03c8ea3fcd1/fx1.jpg

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