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Targeting Premature Renal Aging: from Molecular Mechanisms of Cellular Senescence to Senolytic Trials

Rossana Franzin1, Alessandra Stasi1, Elena Ranieri2

  • 1Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari Aldo Moro, Bari, Italy.

Frontiers in Pharmacology
|May 17, 2021
PubMed

Insights

Cellular senescence drives kidney aging and disease. Targeting senescent cells with senolytics or senomorphics shows promise for treating chronic kidney disease and improving renal transplantation outcomes.

Area of Science:

  • Nephrology
  • Gerontology
  • Cell Biology

Background:

  • Renal aging involves progressive kidney damage, potentially leading to end-stage renal disease.
  • Cellular senescence, characterized by cell cycle arrest and a senescence-associated secretory phenotype (SASP), is increasingly implicated in kidney aging.
  • Preclinical and clinical studies highlight the role of senescent cells in aging and disease.

Purpose of the Study:

  • To review molecular mechanisms triggering premature renal aging.
  • To discuss therapeutic strategies targeting senescent cells in kidney disease.
  • To explore the potential of senotherapeutics in renal transplantation.

Main Methods:

  • Review of molecular pathways including mitochondrial dysfunction, epigenetics, autophagy, DNA damage repair (DDR), and extracellular vesicles.
  • Discussion of senolytics and senomorphics in chronic kidney disease (CKD) models and clinical trials.
  • Overview of senotherapeutics in ex vivo machine perfusion for renal transplantation.

Main Results:

  • Mitochondrial dysfunction, epigenetic alterations, autophagy, DDR, and extracellular vesicles contribute to premature kidney aging.
  • Senolytics and senomorphics demonstrate therapeutic potential in preclinical CKD models.
  • Senotherapeutics may enhance graft quality in renal transplantation.

Conclusions:

  • Cellular senescence is a key driver of renal aging and pathology.
  • Targeting senescent cells offers a promising therapeutic avenue for CKD.
  • Senotherapeutics hold potential for improving renal allograft quality and outcomes.
Keywords:
DNA damage repairextracellular vesiclesmetforminmitochondrial dysfunctionrapamycinrenal ageingsenescencesenolytics

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