Cellular senescence in acute kidney injury: Target and opportunity

Area of Science:

• Nephrology
• Gerontology
• Cell Biology

Background:

• Acute kidney injury (AKI) is a prevalent clinical condition with significant morbidity and mortality.
• AKI pathogenesis involves hemodynamic changes, sepsis, and nephrotoxic agents, leading to renal damage and impaired function.
• Cellular senescence, characterized by irreversible cell cycle arrest, is increasingly recognized as a contributor to AKI.

Purpose of the Study:

• To elucidate the intricate relationship between cellular senescence and AKI.
• To explore novel therapeutic strategies targeting cellular senescence for AKI prevention and treatment.
• To review the impact of senolytics, senostatics, lifestyle interventions, and mesenchymal stem cells (MSCs) on AKI.

Main Methods:

• Review of existing literature on cellular senescence and its role in renal diseases.
• Analysis of mechanisms linking renal cellular senescence to AKI, including oxidative stress, inflammation, telomere shortening, and klotho expression.
• Examination of therapeutic interventions targeting senescent cells in the context of AKI.

Main Results:

• Renal cellular senescence exacerbates AKI through promoting oxidative stress and inflammation, and down-regulating klotho.
• Targeted elimination of senescent cells in vivo has shown potential to improve outcomes in senescence-associated diseases.
• Emerging therapies like senolytics, senostatics, lifestyle modifications, and MSCs demonstrate promise in managing AKI.

Conclusions:

• Cellular senescence is a critical factor in AKI development and progression.
• Interventions aimed at clearing or managing senescent cells represent a promising therapeutic avenue for AKI.
• Further research into senescence-targeting therapies could significantly improve AKI prognosis.