From Senescent Cells to Systemic Inflammation: The Role of Inflammaging in Age-Related Diseases and Kidney...

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.