Premature aging in chronic kidney disease: Decoding senescence biomarkers and therapeutic opportunities

Oct 17, 2025Biochimie

Early aging signs in chronic kidney disease linked to cell aging markers and possible treatments

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Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Chronic kidney disease (CKD) is marked by a premature aging phenotype that involves various biological stressors.

CKD-related stressors may trigger cell cycle arrest and induce senescence in different types of kidney cells.
Senescence is associated with the expression of specific genes and the senescence-associated secretory phenotype (SASP).
This condition could lead to both local damage, such as interstitial fibrosis and endothelial dysfunction, and systemic issues, including cardiovascular risks.
Common biomarkers for identifying senescence include SA-β-gal, p16, p21, p53, and components of SASP like IL-6 and MCP-1.
The potential application of these biomarkers for predicting disease progression and cardiovascular complications in CKD is still underexplored.

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Chronic kidney disease (CKD) is characterized by a premature aging phenotype. CKD-related stressors, such as inflammation, oxidative stress, the buildup of uremic toxins, hyperphosphatemia, mitochondrial dysfunction, sirtuin inhibition, and klotho deficiency, trigger cell cycle arrest, inducing senescence in tubular epithelial cells, endothelial cells, and podocytes, accelerating CKD progression and leading to the expression of senescence-related genes and the senescence-associated secretory phenotype (SASP). This condition promotes local (e.g., interstitial fibrosis, glomerulosclerosis, endothelial dysfunction) and systemic damage, including micro- and macrovascular dysfunction, early vascular aging, and an increased risk of cardiovascular mortality. Markers such as SA-β-gal, p16, p21, p53, and SASP components (e.g., IL-6, MCP-1, MMP-3), as well as telomere shortening and mitochondrial DNA accumulation, are frequently used to identify senescence. Despite their predictive potential, the application of these biomarkers for disease progression and cardiovascular complications remains underexplored in patients with CKD. This narrative review explores the complex relationship between senescence and CKD, reviews key senescence biomarkers, emphasizes their importance for diagnosis, and evaluates the potential of senotherapies to reduce complications of premature aging in this population. INK4a CIP1

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Premature aging in chronic kidney disease: Decoding senescence biomarkers and therapeutic opportunities

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