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普通狨猴(Callithrix jacchus)年龄对血浆代谢组影响的纵向分析。

A longitudinal analysis of the effects of age on the blood plasma metabolome in the common marmoset, Callithrix jacchus.

作者信息

Hoffman Jessica M, Tran ViLinh, Wachtman Lynn M, Green Cara L, Jones Dean P, Promislow Daniel E L

机构信息

Department of Genetics, University of Georgia, 120 Green Street, Athens, GA 30602, USA.

Division of Pulmonary Allergy and Critical Care, Department of Medicine, Emory University, 615 Michael Street, Suite 225, Atlanta, GA 30322,USA; Clinical Biomarkers Laboratory, Department of Medicine, Emory University, 615 Michael Street, Suite 225, Atlanta, GA 30322,USA.

出版信息

Exp Gerontol. 2016 Apr;76:17-24. doi: 10.1016/j.exger.2016.01.007. Epub 2016 Jan 21.

Abstract

Primates tend to be long-lived for their size with humans being the longest lived of all primates. There are compelling reasons to understand the underlying age-related processes that shape human lifespan. But the very fact of our long lifespan that makes it so compelling, also makes it especially difficult to study. Thus, in studies of aging, researchers have turned to non-human primate models, including chimpanzees, baboons, and rhesus macaques. More recently, the common marmoset, Callithrix jacchus, has been recognized as a particularly valuable model in studies of aging, given its small size, ease of housing in captivity, and relatively short lifespan. However, little is known about the physiological changes that occur as marmosets age. To begin to fill in this gap, we utilized high sensitivity metabolomics to define the longitudinal biochemical changes associated with age in the common marmoset. We measured 2104 metabolites from blood plasma at three separate time points over a 17-month period, and we completed both a cross-sectional and longitudinal analysis of the metabolome. We discovered hundreds of metabolites associated with age and body weight in both male and female animals. Our longitudinal analysis identified age-associated metabolic pathways that were not found in our cross-sectional analysis. Pathways enriched for age-associated metabolites included tryptophan, nucleotide, and xenobiotic metabolism, suggesting these biochemical pathways might play an important role in the basic mechanisms of aging in primates. Moreover, we found that many metabolic pathways associated with age were sex specific. Our work illustrates the power of longitudinal approaches, even in a short time frame, to discover novel biochemical changes that occur with age.

摘要

灵长类动物往往因其体型而寿命较长,人类是所有灵长类动物中寿命最长的。有令人信服的理由去了解塑造人类寿命的潜在年龄相关过程。但正是我们漫长的寿命使得这个研究极具吸引力的同时,也使其研究格外困难。因此,在衰老研究中,研究人员转向了非人类灵长类动物模型,包括黑猩猩、狒狒和恒河猴。最近,普通狨猴(Callithrix jacchus)因其体型小、易于圈养以及寿命相对较短,被认为是衰老研究中特别有价值的模型。然而,对于狨猴衰老过程中发生的生理变化知之甚少。为了开始填补这一空白,我们利用高灵敏度代谢组学来确定普通狨猴与年龄相关的纵向生化变化。我们在17个月的时间里,在三个不同的时间点测量了血浆中的2104种代谢物,并对代谢组进行了横断面和纵向分析。我们在雄性和雌性动物中都发现了数百种与年龄和体重相关的代谢物。我们的纵向分析确定了横断面分析中未发现的与年龄相关的代谢途径。富含与年龄相关代谢物的途径包括色氨酸、核苷酸和异生物质代谢,这表明这些生化途径可能在灵长类动物衰老的基本机制中发挥重要作用。此外,我们发现许多与年龄相关的代谢途径具有性别特异性。我们的工作说明了纵向研究方法的力量,即使在短时间内,也能发现随着年龄增长而发生的新的生化变化。

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