This is a very readable review, for all that the authors have stapled together two quite distinct topics into the one binder. Firstly, cellular senescence in various cell types in the cardiovascular system and its role in driving the onset and progression of cardiovascular disease. Secondly, efforts to develop cell therapies to treat cardiovascular disease, including the present generation of stem cell therapies that largely reduce inflammation without achieving any other goals, and further the attempts to induce regeneration and restoration of lost function by delivering replacement cells that are intended to survive, integrate, and support the age-damaged local cell populations.
The issue of population aging presents a significant challenge for many countries, and the related physical health implications have been receiving increasing attention. Senescence impacts several aspects of the cardiovascular system, contributing to diseases such as atherosclerosis, myocardial infarction (MI), pulmonary hypertension, and heart failure (HF). In recent decades, scientists have significantly advanced in understanding the molecular and cellular processes involved in cardiovascular aging, including telomere shortening and damage, oxidative stress, mitochondrial dysfunction, and DNA damage. Molecules such as p53, p21, and p16Ink4a, along with enhanced signals for SA-β-gal, are commonly used to detect senescent cells.
Researchers have identified pathways and factors that could be potential targets for treating or alleviating cardiovascular aging. Furthermore, the rapid advancement of regenerative medicine, including mesenchymal stem cell (MSC) and induced pluripotent stem cell (iPSC) transplantation, has positioned heart regeneration as a promising strategy for addressing age-related cardiovascular diseases. This review summarizes the current understanding of senescent cells, such as cardiomyocytes, endothelial cells, fibroblasts/myofibroblasts, and vascular smooth muscle cells, and their roles in associated cardiovascular diseases. We will also discuss recent factors contributing to cardiovascular aging, including but not limited to Akt and AMPK, and emphasize the potential of heart regeneration research and insights into future regenerative therapies for cardiovascular aging.
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