The Inflammaging-Redox-InflammamiR Axis in Metabolic Aging: From Diagnostic Clusters to Integrated Risk Phenotypes

Age-associated metabolic dysfunction is commonly defined by abnormalities in adiposity, glucose regulation, lipid metabolism, and blood pressure. Although clinically useful, these criteria do not fully capture the biological heterogeneity that explains why older adults with similar metabolic profiles may follow divergent trajectories toward type 2 diabetes, cardiovascular disease, metabolic dysfunction-associated steatotic liver disease, frailty or multimorbidity. This narrative Review summarizes clinical, translational, and mechanistic evidence on the biological processes that shape metabolic aging, with particular emphasis on inflammaging, immunosenescence, cellular senescence, oxidative stress, mitochondrial dysfunction, adipose tissue dysfunction, endothelial injury, and inflammation-related microRNAs. We first discuss how chronic low-grade inflammation and immune remodeling alter the interpretation of conventional metabolic syndrome components in older adults. We then review redox imbalance and mitochondrial stress as amplifiers of insulin resistance, lipid injury, vascular dysfunction, and tissue remodeling. The review also examines inflammation-related microRNAs, including circulating and extracellular-vesicle-associated miRNAs, as post-transcriptional regulators that may connect inflammatory, metabolic, and redox pathways. Finally, we discuss how conventional metabolic markers may be integrated with inflammatory mediators, oxidative-stress indicators, adipokines, endothelial and senescence-related markers, and miRNA profiles to improve biological interpretation of metabolic risk. Within this context, we present the Inflammaging-Redox-InflammamiR Axis as a conceptual framework for organizing these overlapping mechanisms rather than as an established diagnostic or causal model. The proposed biomarker tiers and candidate risk phenotypes are author-derived, hypothesis-generating constructs intended to guide future longitudinal and interventional research. Clinical translation will require standardized assays, longitudinal validation, external replication, and intervention studies.