Multiomic profiling of canine immune and metabolic aging in a cohort of young and senior beagles.

Introduction: Developing a comprehensive understanding of canine aging requires integration of immune, metabolic, and genetic changes across molecular layers. While high-throughput omics have been widely applied to human aging, canine studies have typically used single modalities or small cohorts, limiting systems-level insight, particularly for immune and metabolic aging. To address this gap, we generated a multiomic immune and metabolic aging reference in a cohort of senior and young beagle dogs. Methods: We performed untargeted serum metabolomics in 50 canines (25 senior and 25 young). Additionally, we collected clinical biomarkers and measured gene expression from whole blood using bulk RNA sequencing (bulk RNAseq) from a subset of 39 canines (19 senior, 20 young). We also leveraged single-cell RNA sequencing (scRNAseq) from peripheral blood mononuclear cells (PBMCs) on a subset of 30 canines (15 senior, 15 young). Results: Obtaining ~318,000 PBMC transcriptomes-comprising the largest canine single-cell dataset to date-we resolved 27 distinct immune populations. Age-associated shifts were characterized by loss of naïve lymphocytes with expansion of selected myeloid and Th1-like effector subsets. This was reinforced by remodeling across the transcriptome and metabolome, including coordinated suppression of cell-cycle, DNA repair, and mitochondrial pathways in adaptive immune cells, enrichment of inflammatory signaling in innate immune cells, and depletion of ether-linked lipids and other membrane-associated lipids in serum. To demonstrate the utility of this reference, we leveraged external resources to prioritize a set of candidate genes, including Discussion: These findings characterize the immunometabolic landscape of aging in canine blood, creating a blueprint for identifying interventions to promote healthy aging and longevity.