Understanding cardiac senescence one cell type at a time.

Cellular senescence, a hallmark of aging, is defined as a state of stress-induced proliferative arrest while maintaining viability and metabolic activity [1,2] . Senescence was first characterized in vitro by Leonard Hayflick in WI-38 lung fibroblasts after replicative exhaustion and critical telomere shortening [3] . Eventually, senescence was observed in multiple cell types including those of cardiovascular origin (cardiomyocytes, cardiac fibroblasts, endothelial cells, etc.), and in multiple contexts [4] . For example, acute senescence was found to be critical for embryogenesis, injury response, and wound healing [2] , whereas chronic senescence, while initially tumor suppressive, appeared to be associated with a decline in tissue function and even tumor promotion in aging [5] . Acute cellular senescence plays an important physiological role in cardiac development and regeneration, while senescent cells accumulate in the heart with age, leading to an age-related decline in cardiac function [1,4] . Accordingly, recent studies have linked cellular senescence and the associated release of inflammatory components to cardiac pathologies. However, the exact role of senescent cells in these diseases is unclear, and in some cases, both adverse and beneficial effects have been reported. Therefore, a more complete understanding of cellular senescence promises new insights into disease pathophysiology and will provide new avenues for disease prevention and treatment.