Transcriptomic and intervention evidence reveals domestic dogs as a promising model for anti-inflammatory investigation

Domestic dogs have great potential to expand our understanding of the determinants of aging. To understand the aging pattern of domestic dogs and evaluate whether they can be used as an aging model, we performed RNA sequencing on white blood cells from domestic dogs aged 1-9 years and treated aged dogs with classical antiaging approaches. We obtained 30 RNA sequencing libraries and identified 61 age-associated genes with dynamic changes, the majority of which were related to metabolism and immune function, which may be predominant biomarkers for aging in dogs. We next treated aged dogs with canine mesenchymal stem cells (cMSCs), nicotinamide mononucleotide, and rapamycin to determine whether and how they responded to the antiaging interventions. The results showed that these treatments can significantly reduce the level of inflammatory factors (IL-6 and TNF-alpha). MSCs effectively improved the heart functions of aged dogs. Three key potential age-related genes (PYCR1, CCRL2, and TOX) were reversed by MSC treatment, two of which (CCRL2 and TOX) are implicated in immunity. Overall, we profiled the transcriptomic pattern of domestic dogs and revealed that they may be a good model of aging, especially in anti-inflammatory investigations. We profiled age-related transcriptome of domestic dogs and found that inflammation-associated genes are significantly differentially expressed. We further treated aged dogs with canine mesenchymal stem cells (MSCs), nicotinamide mononucleotide, and rapamycin, all of which can significantly reduce the proinflammatory factors in plasma (e.g., IL-6 and TNF-alpha). Of note is that MSCs effectively improved the heart function and reversed the expression of some age- and inflammation-related genes in aged dogs, suggesting domestic dogs as a promising model for anti-inflammatory investigation.image