Cellular senescence and cell therapy in cardiovascular diseases

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 p16 Ink4a , 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.