Sex-stratified immune patterns across the canine lifespan and short-term responses to geroprotective interventions

Canine models are invaluable for translational geroscience, but natural sex-associated immune aging remains underinvestigated. Here, we characterize the age-associated hematologic and serum cytokine profiles in a controlled cross-sectional cohort of 80 intact laboratory Beagles spanning 1 to 11 years of age. Canine immune aging is heterogeneous and non-linear. While several absolute leukocyte counts declined with age before rising again in geriatric dogs, serum cytokines exhibited distinct, sex-stratified patterns. Although more cytokines varied significantly with age in males than in females, formal age-by-sex interactions did not remain significant after false discovery rate correction. To explore short-term geroprotective responses, we evaluated 24 young beagles following a 90-day intervention with rapamycin, canagliflozin, or dietary restriction. Rapamycin was associated with the broadest endpoint cytokine response. Canagliflozin showed narrower cytokine differences alongside descriptive body-weight reduction, whereas dietary restriction reduced body weight without altering measured immune endpoints. Given the small group sizes and endpoint-only cytokine measurements, these intervention findings remain exploratory and hypothesis-generating. Together, our findings describe stage-specific hematologic changes and sex-stratified cytokine patterns across the canine lifespan and provide a basis for future longitudinal studies.