Canine Aging Models Reveal Common Mechanisms of Metabolic Syndrome in Mammals

Abstract

This study compared metabolic syndrome mechanisms between 120 dogs (60 young, 60 senior) and 120 humans (60 young, 60 older) through cross-species analysis of aging-related metabolic and inflammatory profiles. Age-associated insulin resistance showed parallel progression, with HOMA-IR increasing 134% in aging dogs and 120% in humans. Inflammatory pathway analysis revealed high conservation, particularly NF-κB signaling (conservation scores: 0.89 dogs, 0.90 humans), with concordant TNF-α (r=0.75, p<0.001) and IL-6 (r=0.73, p<0.001) elevation and adiponectin suppression. PPARG showed consistent downregulation (r=-0.74 dogs, r=-0.77 humans), while SIRT1-AMPK axis demonstrated parallel suppression. Cross-species biomarker correlations exceeded 0.70 for key metabolic parameters. Pathway analysis identified shared inflammation-insulin resistance mechanisms, with TLR4 expression correlating with metabolic dysfunction in both species. These findings validate companion dogs as valuable metabolic syndrome models, offering bidirectional translational opportunities for therapeutic development benefiting human and veterinary medicine through One Health approaches.