Effects of age on hepatic gene expression profiles of healthy adult dogs

The objective of this experiment was to use microarray technology to generate hepatic gene expression profiles of healthy young adult and senior dogs. Identifying differentially expressed genes or altered metabolic pathways in elderly dogs may highlight metabolic differences and requirements of this age group. Six senior (11 years old at baseline) and six weanling (8 weeks old at baseline) female beagles were randomly assigned to either a high-fat, low-fiber diet (diet 1) or a low-fat, high-fiber diet (diet 2). Dogs remained in the experiment for 12 months. Total cellular RNA was isolated from liver samples using Trizol (Invitrogen, Carlsbad, CA) and was hybridized to Affymetrix GeneChip Canine Genome Arrays (Affymetrix, Santa Clara, CA) as per the manufacturer's instructions. After microarray normalization procedures, data were analyzed using the mixed-models procedure of SAS (SAS Institute, Cary, NC). Transcripts with a P <.01 (after a false-discovery rate adjustment) and greater than twofold change were considered significantly different among groups. Because significant interactions between age and diet were observed, results are reported in this manner. A total of 607 and 451 transcripts were differentially expressed in senior versus young adult dogs fed diets 1 and 2, respectively. Of interest herein, many of the genes differentially expressed in senior dogs are known to have biologic functions pertaining to metabolism (e.g., glyceraldehyde-3-phosphate dehydrogenase, cytochrome P450 enzymes), hormone and nutrient binding and transport (e.g., fatty acid-binding protein, glutamate transporter, thyroid hormone receptor), protein biosynthesis (e.g., eukaryotic translation elongation factor), and immune function (e.g., major histocompatibility complex class II dog leukocyte antigen). To our knowledge, this is the first published report using microarrays to generate hepatic gene expression profiles of senior dogs. Results may be used as the foundation for future nutrigenomic experiments aimed at molecularly characterizing the metabolic status of aged versus young dogs, aiding in the formulation of diets tailored to meet the unique needs of senior dogs.