Multi-marker approaches are well suited for untangling the intrinsic complexity of aging and related conditions. Herein, we quantified (1) baseline concentrations of a panel of geroscience biomarkers pertaining to four biological domains (i.e., metabolism, inflammation, vascular/organ dysfunction and cellular senescence, and neurodegeneration) in individuals aged ≥60 years; (2) investigated linear and non-linear changes in biomarker levels over a 6-year period according to age and sex; and (3) described the relationships among geroscience biomarkers at baseline and follow-up. We found that repeated measures of age-dependent changes of 47 blood-borne biomarkers over 6 years had differential associations depending on the biological domains. The most relevant biomolecules in the associations between age and repeated assessments were (1) adiponectin, C-peptide, renin (metabolism), (2) CXCL10, IL-1α, IL-1β, IL-6, IL-10, IL-12p70, MPO (inflammation), (3) cystatin C, MMP7, MMP12, VCAM-1 (vascular/organ dysfunction and cellular senescence), and (4) S100B and Tau protein (neurodegeneration). Among these molecules, a negative association with increasing age was found for IL-1α, IL-1β, IL-12p70, S100B, and Tau protein. Non-linear relationships were also identified with age for IGFBP-1, leptin, β2M, TNFRSF1B, fibrinogen, GDF-15, N-cadherin, and BDNF. Our results indicate that inflammatory and metabolic biomolecules are strongly associated with aging over 6 years of follow-up. Whether the biological pathways reflected by these biomarkers contribute to the aging process or are associated with negative health-related events needs to be explored through comprehensive multi-omics longitudinal analysis in larger cohorts.