Cellular metabolism and IL-6 concentrations during stimulated inflammation in primary fibroblasts from small and large dog breeds as they age

The immune system undergoes marked changes during aging characterized by a state of chronic, low-grade inflammation termed 'inflammaging'. We explore this phenomenon in domestic dogs, which are the most morphologically and physiologically diverse group of mammals, with the widest range in body sizes for a single species. Additionally, smaller dogs tend to live significantly longer than larger dogs across all breeds. Body size is intricately linked to mass-specific metabolism and aging rates, which suggests that dogs are exemplary for studies in inflammaging. Dermal fibroblast cells play an important role in skin inflammation, making them a good model for inflammatory patterns across dog breed, body sizes and ages. Here, we examined aerobic and glycolytic cellular metabolism, and IL-6 concentrations in primary fibroblast cells isolated from small and large dog breeds, that were either recently born puppies or old dogs after death. We found no differences in cellular metabolism when isolated fibroblasts were treated with lipopolysaccharide (LPS) from Escherichia coli to stimulate an inflammatory phenotype. Unlike responses observed in mice and humans, there was a less drastic amplification of IL-6 concentration after LPS treatment in the geriatric population of dogs compared with recently born dogs. In young dogs, we also found evidence that untreated fibroblasts from large breeds had significantly lower IL-6 concentrations than observed for smaller breeds. This implies that the patterns of inflammaging in dogs may be distinct and different from other mammals commonly studied.