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.

Plant-derived natural products remain a major source of anticancer chemical diversity, yet much of the preclinical literature still describes their activity through compound-centered readouts such as IC₅₀ values, reactive oxygen species generation, mitochondrial depolarization, BCL-2-family remodeling, caspase activation, and PI3K/Akt or NF-κB inhibition. Although informative, these mechanisms do not fully explain why the same phytochemical induces apoptosis in some cancer cells, and cytostasis or adaptation in others, while normal cells frequently activate cytoprotective responses. Rather than replacing conventional compound-centered approaches, we integrate established concepts into a complementary vulnerability-state framework for interpreting plant-derived natural-product-induced selective apoptosis. In this framework, selective apoptosis occurs when phytochemical-induced stress intersects with pre-existing cancer-cell vulnerabilities, overwhelms adaptive buffering, and remains below the injury threshold of normal cells. We organize current evidence around redox imbalance, mitochondrial priming, membrane remodeling, ion-channel and cell-volume dysregulation, and survival-pathway addiction, emphasizing that pathway modulation becomes mechanistically meaningful when linked to differential cellular sensitivity. We further highlight membrane–ion biology as an underexplored contributor to phytochemical responses and discuss how chemical standardization, orthogonal cell-death assays, matched normal-cell models, organoids, and pharmacokinetic/pharmacodynamic considerations can advance the field from descriptive cytotoxicity toward mechanism-informed phytopharmacology.

Diabetic kidney disease (DKD) remains one of the most severe microvascular complications of type 2 diabetes mellitus (T2DM) and a leading cause of chronic kidney disease (CKD) worldwide. Nevertheless, despite considerable progress in elucidating its molecular background, early diagnosis and accurate stratification of disease progression remain challenging when relying on conventional clinical biomarkers such as albuminuria and estimated glomerular filtration rate (eGFR). Growing evidence indicates that DKD is driven by interconnected pathogenic mechanisms, including chronic hyperglycemia, activation of the protein kinase C (PKC) signaling pathway, renin–angiotensin–aldosterone system (RAAS) dysregulation, oxidative stress, inflammatory cascades, and immune system activation involving Toll-like receptors (TLR) and the NLRP3 inflammasome. These processes collectively contribute to endothelial dysfunction, podocyte injury, extracellular matrix accumulation, and progressive renal fibrosis. Exosomes and their molecular cargo, particularly miRNAs, have emerged as promising regulators and non-invasive biomarkers reflecting ongoing renal injury. Urinary exosomal microRNAs (uEV-miRNAs) are of interest due to their stability in biological fluids and their direct origin from nephron segments, enabling real-time reflection of renal pathophysiology. Accumulating studies suggest that differentially expressed microRNAs (miRNAs), including miR-21-5p, miR-30a-5p, miR-192-5p, and miR-142-3p, are closely associated with key pathways in DN. However, their clinical translation remains limited by methodological heterogeneity, the lack of standardized isolation protocols, and insufficient validation in large longitudinal cohorts. This review navigates the current landscape of knowledge on the molecular mechanisms underlying DKD and examines the emerging role of uEV-miRNAs as diagnostic biomarkers. Altogether, uEV-miRNAs offer a promising avenue for improving early detection, risk stratification, and disease monitoring in DKD.