Understanding and targeting senescence in kidney disease.

Area of Science:

• Nephrology
• Cellular Biology
• Gerontology

Background:

• Chronic kidney disease (CKD) affects over 850 million globally, posing significant morbidity, mortality, and healthcare challenges.
• Current CKD treatments primarily manage risk factors, with limited options to halt disease progression at the cellular level.
• Cellular senescence, characterized by irreversible cell-cycle arrest and pro-inflammatory signaling, is increasingly recognized as a key driver in CKD pathogenesis, particularly in tubular epithelial cells (TECs).

Purpose of the Study:

• To review the contribution of cellular senescence to kidney aging and CKD progression.
• To outline the molecular mechanisms and biomarkers associated with renal senescence.
• To highlight emerging senotherapeutic strategies for CKD management.

Main Methods:

• Review of existing literature on cellular senescence in kidney disease.
• Analysis of preclinical studies on senolytics and senomorphics in experimental models.
• Discussion of challenges and future directions for clinical translation.

Main Results:

• Senescent TECs accumulate in injured kidneys, promoting inflammation, fibrosis, and impaired regeneration.
• Diverse stressors like ischemia-reperfusion, metabolic stress, and uremic toxins trigger renal senescence.
• Preclinical senolytic and senomorphic therapies have demonstrated potential in reducing renal fibrosis and preserving kidney function.

Conclusions:

• Cellular senescence is a critical, potentially modifiable factor in kidney disease.
• Senotherapeutic approaches offer novel avenues for CKD treatment.
• Further research is needed to develop non-invasive biomarkers and address cellular heterogeneity for successful clinical translation.