Elsevier

Journal of Cardiology

Volume 74, Issue 4, October 2019, Pages 313-319
Journal of Cardiology

Review
Cellular senescence in cardiac diseases

https://doi.org/10.1016/j.jjcc.2019.05.002Get rights and content
Under a Creative Commons license
open access

Highlights

  • Cardiac cells become senescent with aging.

  • Cellular senescence is mostly pathological in failing hearts.

  • Senolytics reverse aging phenotype in dysfunctional hearts.

Abstract

Replicative capacity of somatic cells is limited. It indicates that aging also develops at the cellular level, and this is described as “cellular senescence”. Senescent cells become flattened, enlarged, and irreversibly lose capacity for proliferation. Lack of specific and conclusive markers for cellular senescence makes it difficult to comprehensively define and understand this biological process especially in vivo. Molecules including p53, p21, p16Ink4a, p38MAPK, and γH2AX, telomere attrition, enhanced signals for SA-β-gal, etc. are widely used to detect senescent cells, but these are indirect indicators of cellular senescence, and biological markers reflecting direct evidence need to be established. Genetic profiles are altered in senescent cells, letting these cells secrete pro-inflammatory molecules. Aging or age-related disorders including heart failure and atherosclerotic diseases link with an accumulation of cells undergoing cellular senescence in cardiovascular systems including heart and vessels. Senescent cells become pathogenic in most cases by mediating chronic sterile inflammation and tissue remodeling. A recent conceptual as well as technical breakthrough in this research area is “senolysis”, meaning the specific elimination of senescent cells. Genetic as well as pharmacological models with senolysis contributed to reverse aging phenotypes and ameliorated pathologies in age-related disorders without enhancing the risk of tumorigenesis, and opened a new avenue for aging research. Several compounds are identified as senolytics, and some are already tested in clinical settings. It was recently reported that senolysis reverses aging phenotype in cardiovascular disorders. Generating therapies targeting suppression or elimination of senescent cells would inhibit the progression of undesirable aspects of aging, and become promising therapies for cardiac diseases.

Keywords

Cellular senescence
Heart failure
Senolysis

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