Cellular Senescence in Arterial Diseases

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.

A Unified Model of Age-Related Cardiovascular Disease

“…A similar causal cascade occurs in aneurysms, as the cell aging of the vascular walls results in structural deterioration. The vascular mesenchymal stromal cells (VMSCs) from aortic aneurysms are more senescent than those from healthy aortas, and medial smooth muscle cells taken from aneurysms are likewise more senescent than cells from normal arteries in the same individual [ 121 , 122 , 123 ].…”

The Effects of Resveratrol on Telomeres and Post Myocardial Infarction Remodeling

“…Autophagy is highly regulated in cardiac tissue; excessive autophagy may cause cardiomyopathy and heart failure; they concluded that regulation of autophagy is important for preventing myocardial aging [ 17 ]. According to Shimizu et al senescent cells are pro-inflammatory and cause chronic sterile inflammation [ 18 ]. Senescent cell accumulation is considered pathogenic in the cardiovascular system as it leads to vascular remodeling; novel approaches have allowed for eliminating senescent cells in vivo and in vitro; senolysis is the term used for this process [ 18 ].…”

“…According to Shimizu et al senescent cells are pro-inflammatory and cause chronic sterile inflammation [ 18 ]. Senescent cell accumulation is considered pathogenic in the cardiovascular system as it leads to vascular remodeling; novel approaches have allowed for eliminating senescent cells in vivo and in vitro; senolysis is the term used for this process [ 18 ]. Senolysis could reverse aging-related cardiovascular pathologies without potential for tumorigenesis [ 18 ].…”

“…Senescent cell accumulation is considered pathogenic in the cardiovascular system as it leads to vascular remodeling; novel approaches have allowed for eliminating senescent cells in vivo and in vitro; senolysis is the term used for this process [ 18 ]. Senolysis could reverse aging-related cardiovascular pathologies without potential for tumorigenesis [ 18 ]. Cardiac myocytes ( have the most abundant mitochondrial population ) are terminally differentiated cells with low regenerative capacity in the adult [ 19 ].…”

Vascular Damage in the Aorta of Wild-Type Mice Exposed to Ionizing Radiation: Sparing and Enhancing Effects of Dose Protraction

“…For comparison, we also included a series of non-irradiated groups such as aged mice and apolipoprotein E-deficient (ApoE −/− ) mice as positive controls each for senescent and DCS phenotypes, respectively. This was because irradiation often induces a premature (accelerated) senescence-like phenotype (e.g., in vascular endothelial cells (VECs) [ 12 , 13 ]), a senescent phenotype is involved in DCS etiology (e.g., in arterial disease [ 14 ]), and wild-type mice exhibit prelesional changes in the circulatory system (i.e., changes preceding DCS lesion formation), but not lesional changes (i.e., DCS phenotype).…”