Aging is characterized by a chronic, low-grade inflammatory state known as inflammaging, which closely interacts with immunosenescence—the gradual deterioration of immune function. Together, these processes contribute to tissue dysfunction and the development of age-related diseases. This review explores the cellular and molecular mechanisms underlying inflammaging, including mitochondrial dysfunction, telomere attrition, impaired autophagy, and gut microbiota dysbiosis. A particular emphasis is given to the senescence-associated secretory phenotype (SASP), which sustains a pro-inflammatory microenvironment and exacerbates tissue damage. We further discuss the impact of inflammaging on major age-related pathologies, with a focus on the kidney as a paradigmatic model of age-related decline, where inflammaging and cellular senescence contribute to chronic kidney disease (CKD) and impaired regeneration. Finally, we summarize emerging therapeutic strategies such as senolytics, senomorphics, immunomodulation, and lifestyle interventions, aimed at reducing the burden of senescent cells, mitigating inflammaging and extending healthspan.

Cystic fibrosis (CF) airways are affected by a deranged repair of the damaged epithelium resulting in altered regeneration and differentiation. Previously, we showed that human amniotic mesenchymal stem cells (hAMSCs) corrected base defects of CF airway epithelial cells via connexin (CX)43-intercellular gap junction formation. In this scenario, it is unknown whether hAMSCs, or fibroblasts sharing some common characteristics with MSCs, can operate a faster repair of a damaged airway epithelium. A tip-based scratch assay was employed to study wound repair in monolayers of CFBE14o- cells (CFBE, homozygous for the F508del mutation). hAMSCs were either co-cultured with CFBE cells before the wound or added to the wounded monolayers. NIH-3T3 fibroblasts (CX43+) were added to wounded cells. HeLa cells (CX43-) were used as controls. γ-irradiation was optimized to block CFBE cell proliferation. A specific siRNA was employed to downregulate CX43 expression in CFBE cells. CFBE cells showed a delayed repair as compared with wt-CFTR cells (16HBE41o-). hAMSCs enhanced the wound repair rate of wounded CFBE cell monolayers, especially when added post wounding. hAMSCs and NIH-3T3 fibroblasts, but not HeLa cells, increased wound closure of irradiated CFBE monolayers. CX43 downregulation accelerated CFBE wound repair rate without affecting cell proliferation. We conclude that hAMSCs and fibroblasts enhance the repair of a wounded CF airway epithelium, likely through a CX43-mediated mechanism mainly involving cell migration.

Background/Objectives: Renal cell carcinoma (RCC) is a common and often asymptomatic malignancy with limited treatment options for advanced stages. Chronic inflammation and cellular senescence—collectively termed “inflammaging”—are emerging as key contributors to tumor progression. This study aimed to investigate the expression of inflammaging-related markers in RCC tissues, focusing on the role of PTX3, IL-6, and senescence-associated proteins in the tumor microenvironment. Methods: A retrospective cohort of 57 patients with clear cell RCC who underwent nephrectomy was analyzed. Formalin-fixed paraffin-embedded samples from tumor, peritumoral, and normal renal tissues were examined using confocal immunofluorescence microscopy to assess PTX3, IL-6, p21, and p16 expression. Senescence-associated β-galactosidase staining was performed to identify senescent cells. Serum IL-6 levels were measured by ELISA, and survival analysis was conducted using Kaplan–Meier curves and Cox regression analysis. Results: PTX3 and IL-6 were significantly upregulated in both peritumoral and tumor tissues compared to normal kidney samples (p < 0.001). Expression of senescence markers p21 and p16 were elevated in peritumoral areas (p < 0.001) as compared to normal renal tissues, but their expression was reduced or absent in the tumor core. High-grade and high-stage tumors exhibited stronger PTX3 and IL-6 expression and lower levels of cell cycle inhibitors (p < 0.001). Patients with elevated serum IL-6 levels had significantly lower 5-year cancer-specific survival (p < 0.005) and shorter progression-free survival (p < 0.001). Conclusions: Our findings suggest that peritumoral tissue in RCC exhibits a senescent and proinflammatory phenotype that may support tumor progression. PTX3 and IL-6 are potential biomarkers of disease severity and prognosis. Targeting inflammaging pathways could offer new therapeutic strategies for RCC, particularly in aggressive disease forms.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by the loss of self-tolerance to nuclear and cytoplasmic antigens, triggering immune activation and tissue inflammation. Lupus nephritis (LN) is a major determinant of disease-related morbidity, disability, chronic kidney disease progression, kidney failure, and mortality in SLE, affecting approximately 30% of patients at diagnosis and up to 50–60% within the first decade. This review examines the disease’s pathogenic mechanisms, emphasizing the innate immune system’s role in the loss of self-tolerance and subsequent activation of the adaptive immune response. Mechanisms include dysregulated cell death pathways, impaired clearance of nucleic acid-containing debris and immune complexes, and involvement of antigen-presenting cells and other innate immune cells. These processes lead to the clonal expansion of autoreactive lymphocytes, generating effector T cells, memory B cells, and plasma cells that produce autoantibodies, resulting in renal injury. The review further explores the immunological processes driving kidney damage, beginning with autoantibody binding and immune complex deposition, followed by complement-mediated microvascular injury, kidney stromal cell activation, and leukocyte recruitment. Lastly, it discusses LN treatment strategies, from traditional to novel targeted therapies, with a focus on their systemic immunologic impacts and the protection of podocytes.

Chronic kidney disease (CKD) represents a major global health challenge, affecting more than 10% of the population and contributing substantially to morbidity and premature mortality. Growing evidence identifies oxidative stress and mitochondrial dysfunction as central drivers of renal injury and disease progression across diverse etiologies. The kidney is one of the most mitochondria-rich organs in the body, reflecting the high bioenergetic demands required for tubular reabsorption and metabolic homeostasis. Disruption of mitochondrial oxidative phosphorylation, excessive production of reactive oxygen species (ROS), and impaired mitochondrial quality control mechanisms promote tubular injury, inflammation, and fibrosis. In particular, dysfunction of the electron transport chain, activation of NADPH oxidase isoforms—especially NOX4—and alterations in mitochondrial dynamics create a vicious cycle of oxidative damage and bioenergetic failure. Emerging evidence highlights the importance of mitochondrial quality control pathways, including fusion–fission balance, PINK1/Parkin-mediated mitophagy, and mitochondrial biogenesis regulated by PGC-1α and TFAM. Recent studies have also identified additional mechanisms linking mitochondrial dysfunction to CKD progression, including ferroptosis, epigenetic regulation of mitochondrial genes, and mitochondrial DNA release acting as damage-associated molecular patterns that activate innate immune pathways. At the clinical level, redox and mitochondrial biomarkers—such as F2-isoprostanes, 8-hydroxy-2′-deoxyguanosine, advanced oxidation protein products, and circulating mitochondrial DNA—may improve early diagnosis and risk stratification. Therapeutically, both established nephroprotective drugs and emerging mitochondria-targeted interventions aim to restore mitochondrial homeostasis and represent promising strategies for slowing CKD progression.

Chronic kidney disease (CKD) represents a major global health challenge, affecting more than 10% of the population and contributing substantially to morbidity and premature mortality. Growing evidence identifies oxidative stress and mitochondrial dysfunction as central drivers of renal injury and disease progression across diverse etiologies. The kidney is one of the most mitochondria-rich organs in the body, reflecting the high bioenergetic demands required for tubular reabsorption and metabolic homeostasis. Disruption of mitochondrial oxidative phosphorylation, excessive production of reactive oxygen species (ROS), and impaired mitochondrial quality control mechanisms promote tubular injury, inflammation, and fibrosis. In particular, dysfunction of the electron transport chain, activation of NADPH oxidase isoforms—especially NOX4—and alterations in mitochondrial dynamics create a vicious cycle of oxidative damage and bioenergetic failure. Emerging evidence highlights the importance of mitochondrial quality control pathways, including fusion–fission balance, PINK1/Parkin-mediated mitophagy, and mitochondrial biogenesis regulated by PGC-1α and TFAM. Additional mechanisms include ferroptosis, epigenetic regulation, mitochondrial DNA-mediated innate immune activation, and Na⁺/K⁺-ATPase-linked redox signaling. At the translational level, redox and mitochondrial biomarkers and targeted therapies are biologically compelling, but the evidence is uneven: most candidate biomarkers remain insufficiently standardized, and direct mitochondria-targeted interventions are supported predominantly by preclinical studies or small human proof-of-concept trials. This review therefore emphasizes not only mechanistic advances but also conflicting findings, model limitations, and the barriers that currently separate experimental efficacy from clinically meaningful CKD outcomes.