Poly(A) RNA sequencing reveals age-related differences in the prefrontal cortex of dogs

Dogs may possess a unique translational potential to investigate neural aging and dementia because they are prone to age-related cognitive decline, including an Alzheimer’s disease–like pathological condition. Yet very little is known about the molecular mechanisms underlying canine cognitive decline. The goal of the current study was to explore the transcriptomic differences between young and old dogs’ frontal cortex, which is a brain region often affected by various forms of age-related dementia in humans. RNA isolates from the frontal cortical brain area of 13 pet dogs, which represented 7 different breeds and crossbreds, were analyzed. The dogs were euthanized for medical reasons, and their bodies had been donated by their owners for scientific purposes. The poly(A) tail RNA subfraction of the total transcriptome was targeted in the sequencing analysis. Cluster analyses, differential gene expression analyses, and gene ontology analyses were carried out to assess which genes and genetic regulatory mechanisms were mostly affected by aging. Age was the most prominent factor in the clustering of the animals, indicating the presence of distinct gene expression patterns related to aging in a genetically variable population. A total of 3436 genes were found to be differentially expressed between the age groups, many of which were linked to neural function, immune system, and protein synthesis. These findings are in accordance with previous human brain aging RNA sequencing studies. Some genes were found to behave more similarly to humans than to rodents, further supporting the applicability of dogs in translational aging research. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-022-00533-3.