As dogs live longer, they face an increased risk of functional age-related changes, including physiological and behavioral alterations. However, data on these age-related processes in domestic dogs remain limited. In this study, we assessed serum concentrations of cytokines (TNF-α, IL-6, IL-10), personality and cognition using validated scales (Dog Reinforcement Sensitivity Theory Personality Questionnaire (RSTQ-D), Dog Impulsivity Assessment Scale (DIAS), and Canine Cognitive Assessment Scale (CCAS)) in 44 healthy pet dogs from two non-overlapping age groups (1–4 years old and ≥11 years old). Generalized linear models revealed small but significant (p = 0.001) negative effects of age-by-cytokine interactions in predicting sensitivity to RST personality traits related to fear and anxiety in older dogs. Specifically, higher TNF-α and IL-10 levels predicted lower scores on the Fight/Flight/Freeze System (FFFS) and the Behavioral Inhibition System (BIS). These findings provide novel insights into previously unrecognized associations between the immune system and personality in healthy older dogs, possibly contributing to broader profiles of vulnerability or, conversely, resilience. Further research is needed to confirm these associations and clarify their functional meaning. Such knowledge could facilitate the early identification of complex aging-related phenotypes and inform individualized preventive strategies to support the health and well-being of aging companion dogs.

Serum activity of paraoxonase-1 (PON-1) decreases in canine inflammation. This study aimed to evaluate how frequently PON-1 activity is reduced across different disease categories and to assess its potential prognostic significance. PON-1 activity was measured in 482 samples (435 first visit, 47 follow-up) collected during routine clinical activities. The emergency/first-opinion unit (EF) had the highest frequency of low values (18.3%) and lower median PON-1 activity (170.3 U/mL) compared with other units. The proportion of lower values and median PON-1 values were, respectively, significantly higher and lower in acute/severe diseases compared with chronic/mild diseases (13.3 vs. 7.1%; 177.0 vs. 192.9 U/mL) and in hospitalized compared with non-hospitalized dogs (27.7 vs. 4.5%; 150.0 vs. 193.0 U/mL). Low PON-1 activity may predict the need for hospitalization: values < 45.7 U/mL have a likelihood ratio of 14.4. The proportion of lower values and the median Paraoxonase-1 activity did not differ between survivors and non-survivors (18.2 vs. 25.0%; 162.0 vs. 161.3 U/mL). However, PON-1 activity diminished during hospitalization only in non-survivors. PON-1 activity should be measured in routine practice, especially in the EF; hospitalization may be warranted when results are markedly low. Decreases in PON-1 activity during hospitalization may suggest a negative outcome.