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Senescent Cells: A Therapeutic Target in Cardiovascular Diseases

Masayoshi Suda1,2, Karl H Paul1,3, Tohru Minamino2,4

  • 1Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First St., S.W., Rochester, MN 55905, USA.

Cells
|May 13, 2023
PubMed

Insights

Cellular senescence, marked by the accumulation of senescent cells secreting harmful factors, drives cardiovascular diseases. Senolytic therapies targeting these cells show promise for treating age-related cardiovascular conditions.

Area of Science:

  • Gerontology
  • Cardiovascular Medicine
  • Cell Biology

Background:

  • Cellular senescence, characterized by irreversible growth arrest and the secretion of senescence-associated secretory phenotype (SASP) factors, is increasingly implicated in the pathogenesis of age-associated diseases, particularly cardiovascular diseases.
  • Accumulation of senescent cells contributes to tissue dysfunction and inflammation, exacerbating conditions like atherosclerosis, heart failure, and hypertension.

Purpose of the Study:

  • To review the role of cellular senescence in cardiovascular diseases, examining its impact on various cardiovascular cell types.
  • To summarize the current evidence for senolytic drugs and other senotherapeutics in preclinical and clinical settings for cardiovascular conditions.
  • To discuss the future potential and clinical translation of senotherapeutics for cardiovascular diseases.

Main Methods:

  • Literature review of studies investigating cellular senescence in cardiovascular disease models.
  • Analysis of preclinical data on senolytic drugs and senotherapeutics targeting senescent cells.
  • Examination of ongoing and completed clinical trials involving senotherapeutics for age-related diseases.

Main Results:

  • Senescent cells, including endothelial cells, vascular smooth muscle cells, and cardiomyocytes, contribute to cardiovascular pathology through SASP.
  • Senolytic therapies have demonstrated efficacy in preclinical models by clearing senescent cells and alleviating cardiovascular dysfunction.
  • Clinical trials are exploring the safety and efficacy of senolytics for various age-related conditions, with potential cardiovascular benefits.

Conclusions:

  • Cellular senescence is a significant contributor to cardiovascular diseases, making senescent cells a viable therapeutic target.
  • Senolytic drugs and other senotherapeutics offer a promising strategy for preventing, delaying, or treating cardiovascular diseases.
  • Further research and clinical trials are crucial to translate the potential of senotherapeutics into effective treatments for cardiovascular conditions.
Keywords:
SASPatherosclerosiscardiovascular diseasescellular senescencesenolytics

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