The resistance of domestic canine skin-derived fibroblasts to oxidative and non-oxidative chemical injury: implications of breed and body size.

Abstract

Small-breed dogs live significantly longer lives than large-breed dogs, while having higher mass-specific metabolic rates and faster growth rates. Underlying this observed physiological difference across domestic dogs, there must also be differences at other levels of organization that could lead to elucidating what accounts for the disparity in aging rates and life span within this species. At the cellular level, a clear mechanism underlying whole animal traits has not been fully elucidated. Here, we cultured dermal fibroblasts from large and small breed dogs from both young and old age categories and examined the degree of resistance to multiple sources of cytotoxic stress. This included heat (42°C), paraquat, cadmium, and hydrogen peroxide for increasing amounts of time (heat) or increasing concentrations (chemical stressors). We hypothesized that small breed dogs, with longer lifespans, would have greater cellular resistance to stress compared with large breed dogs. Final sample sizes include small puppies (N = 18), large puppy (N = 32), small old (N = 11), and large old (N = 23) dogs. Using a 2 (donor size) by 2 (donor age) between-subjects multivariate analysis of variance, we found that the values for the dose that killed 50% of the cells (LD50) were not significantly different based on donor size (p = 0.45) or donor age (p = 0.20). The interaction was also not significant (p = 0.47). Interestingly, we did find that the degree of resistance to cadmium toxicity was significantly correlated with the degree of resistance to both heat and hydrogen peroxide, but not paraquat (p < 0.01 for both). These data suggest that cellular stress resistance does not differ among domestic dogs as a function of size or age, pointing to other cellular pathways as the mechanistic basis for the observed differences in lifespan.