When a cell becomes senescent it ceases replication, expands in size, and secretes a mix of pro-growth, pro-inflammatory molecules known as the senescence-associated secretory phenotype (SASP). Cells become senescent throughout life, mostly upon reaching the Hayflick limit on replication. Forms of damage, particularly DNA damage that might lead to cancer, the signaling of other senescent cells, and a toxic environment can also provoke cellular senescence. Senescence is also involved in coordinating regeneration from injury. When an individual is young, senescent cells are cleared efficiently by the immune system, but with age this clearance falters. The result is an accumulating burden of senescent cells that disrupt tissue structure and function with their signals.
In today's open access paper, researchers review what is known of the role of cellular senescence in the aging of the heart and vasculature, causing dysfunction that contributes to the various forms of cardiovascular disease. Cardiovascular disease is the greatest cause of human mortality, those deaths largely split between heart failure, heart attack, and stroke. Controlling the burden of senescent cells, such as by preventing the onset of senescence, selectively destroying senescent cells, or at the very least inhibiting the SASP, is hoped to reduce this aspect of aging. There are some caveats, such as whether senescent cells are holding together tissues (or unstable atherosclerotic plaques!) in very late aging, and thus destroying them could be problematic. There should be no such issues for inhibiting the buildup of senescent cells prior to that late stage, however.
The role of cellular senescence in cardiovascular disease
Cardiovascular disease poses a profound global concern for public health, with age standing as a crucial risk factor that contributes significantly to the progressive deterioration of cardiac structure and functionality. In mammals, the aging process is linked to the build-up of senescent cells. During aging, cells undergo mitochondrial dysfunction, DNA damage, and increased activation of the p53/p21 and p16 signaling pathways in response to cellular stress, ultimately contributing to the development and advancement of cardiovascular diseases.
In recent years, cellular senescence has garnered considerable interest as a potential target for alleviating age-related diseases and extending lifespan. Cellular senescence is a hallmark of aging, characterized by a stable cell cycle block accompanied by typical morphological changes in cells and a distinguishable secretory phenotype.
The aim of this review is to provide a comprehensive summary of the role of cellular senescence in cardiovascular disease and related mechanisms. To begin, an overview of the fundamental concepts, characteristics, and biological effects of cellular senescence will be provided. Additionally, we will delve into the regulatory mechanisms of cellular senescence, encompassing the key molecules and signaling pathways involved. Subsequently, our focus will shift to exploring the interconnections between cellular senescence and conditions such as hypertension, atherosclerosis, myocardial infarction, heart failure, arrhythmias, and cardiomyopathy. This exploration aims to illuminate the role of cellular senescence in the development and progression of these diseases.
Finally, we will also explore the impact of targeted cellular senescence-related therapies on the aforementioned cardiovascular diseases. For example, pharmacologically removing or knocking out senescent cells in mice mitigates cardiac hypertrophy and fibrosis induced by cardiac senescence while also facilitating cardiomyocyte regeneration.
View the full article at FightAging
