Department of Animal Sciences, University of Illinois, Urbana, Illinois, United States of America.
PLoS One. 2010 Oct 12;5(10):e13319. doi: 10.1371/journal.pone.0013319.
The liver plays a central role in nutrient and xenobiotic metabolism, but its functionality declines with age. Senior dogs suffer from many of the chronic hepatic diseases as elderly humans, with age-related alterations in liver function influenced by diet. However, a large-scale molecular analysis of the liver tissue as affected by age and diet has not been reported in dogs.
METHODOLOGY/PRINCIPAL FINDINGS: Liver tissue samples were collected from six senior (12-year old) and six young adult (1-year old) female beagles fed an animal protein-based diet (APB) or a plant protein-based diet (PPB) for 12 months. Total RNA in the liver tissue was extracted and hybridized to Affymetrix GeneChip® Canine Genome Arrays. Using a 2.0-fold cutoff and false discovery rate <0.10, our results indicated that expression of 234 genes was altered by age, while 137 genes were differentially expressed by diet. Based on functional classification, genes affected by age and/or diet were involved in cellular development, nutrient metabolism, and signal transduction. In general, gene expression suggested that senior dogs had an increased risk of the progression of liver disease and dysfunction, as observed in aged humans and rodents. In particular for aged liver, genes related to inflammation, oxidative stress, and glycolysis were up-regulated, whereas genes related to regeneration, xenobiotic metabolism, and cholesterol trafficking were down-regulated. Diet-associated changes in gene expression were more common in young adult dogs (33 genes) as compared to senior dogs (3 genes).
Our results provide molecular insight pertaining to the aged canine liver and its predisposition to disease and abnormalities. Therefore, our data may aid in future research pertaining to age-associated alterations in hepatic function or identification of potential targets for nutritional management as a means to decrease incidence of age-dependent liver dysfunction.
肝脏在营养物质和外源性化合物的新陈代谢中起着核心作用，但随着年龄的增长其功能会下降。老年犬会患上许多与人类老年人相似的慢性肝脏疾病，其肝功能的年龄相关性变化受到饮食的影响。然而，目前尚未有关于犬肝脏组织受年龄和饮食影响的大规模分子分析。
方法/主要发现：从六只老年（12 岁）和六只年轻成年（1 岁）雌性比格犬中采集肝脏组织样本，这些狗分别喂食动物蛋白基础饮食（APB）或植物蛋白基础饮食（PPB）12 个月。提取肝脏组织中的总 RNA，并与 Affymetrix GeneChip®犬基因组阵列杂交。使用 2.0 倍的截止值和错误发现率 <0.10，我们的结果表明，有 234 个基因的表达受到年龄的影响，而 137 个基因的表达受到饮食的影响。根据功能分类，受年龄和/或饮食影响的基因参与细胞发育、营养代谢和信号转导。总的来说，基因表达表明，老年犬患肝脏疾病和功能障碍的风险增加，这与人类和啮齿动物的衰老观察结果一致。特别是对于老年肝脏，与炎症、氧化应激和糖酵解相关的基因上调，而与再生、外源性化合物代谢和胆固醇转运相关的基因下调。与饮食相关的基因表达变化在年轻成年犬中更为常见（33 个基因），而在老年犬中则较少（3 个基因）。
我们的研究结果为犬老化肝脏及其对疾病和异常的易感性提供了分子见解。因此，我们的数据可能有助于未来研究与肝脏功能的年龄相关性变化相关的研究，或确定营养管理的潜在目标，以减少与年龄相关的肝功能障碍的发生率。
