J Lipid Atheroscler.  2020 Jan;9(1):79-91. 10.12997/jla.2020.9.1.79.

Cellular Senescence in Arterial Diseases

• Shimizu I
• Minamino T

• KMID: 2470802
• DOI: http://doi.org/10.12997/jla.2020.9.1.79

Abstract

Cell-proliferation potency is limited, as cells cannot proceed through the cell cycle continually. Instead, they eventually show an irreversible arrest of proliferation, commonly referred to as cellular senescence. Following the initial discovery of this phenomenon by Hayflick et al., studies have indicated that cells are also destined to undergo aging. In addition to the irreversible termination of proliferation, senescent cells are characterized by a flattened and enlarged morphology. Senescent cells become pro-inflammatory and contribute to the initiation and maintenance of sustained chronic sterile inflammation. Aging is associated with the accumulation of senescent cells in the cardiovascular system, and in general these cells are considered to be pathogenic because they mediate vascular remodeling. Recently, genetic and pharmacological approaches have enabled researchers to eliminate senescent cells both in vitro and in vivo. The term "senolysis" is now used to refer to the depletion of senescent cells, and evidence indicates that senolysis contributes to the reversal of age-related pathogenic phenotypes without the risk of tumorigenesis. The concept of senolysis has opened new avenues in research on aging, and senolysis may be a promising therapeutic approach for combating age-related disorders, including arterial diseases.

Keyword

Cellular senescence; Arterial diseases; Senolysis

MeSH Terms

Aging
Carcinogenesis
Cardiovascular System
Cell Aging*
Cell Cycle
In Vitro Techniques
Inflammation
Phenotype
Vascular Remodeling

Figure

• 

  Fig. 1 The emerging concept underlying therapies targeting arterial diseases with senolysis. The rejuvenation of senescent vascular cells by senolysis contributes to the suppression of senescence markers such as p53/p21, p16Ink4a, and SA-β-gal, and reverses atherosclerosis. In addition to genetic models, senolysis includes pharmacological models such as the D+Q and ABT263 models. These contribute to the suppression of pathologies in arterial diseases, including peripheral artery disease, coronary artery disease, and aortic aneurysm. D+Q, dasatinib and quercetin; SA-β-gal, senescence-associated beta-galactosidase.

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