Cellular senescence in cardiovascular diseases: Potential age-related mechanisms and implications for treatment

The aging process is associated with a loss of complexity in the dynamics of physiological systems that reduce the ability to adapt to stress, causing frailty and/or age-related diseases. At the cellular level, proliferative and/or oxidative-stress induced cell senescence associated with a pro-inflammatory state may greatly contribute to age-associated impaired tissue and organ functions. Senescence of endothelial and cardiac cells observed over normal aging, appear to be accelerated in age-related diseases and in particular, in cardiovascular disease (CVD). Although the molecular mechanisms of cellular senescence have been extensively studied, a complete understanding of their role in CVD is still limited. Cardiac, endothelial (EC), vascular smooth muscle (VSMC), leukocytic and stem cells (endothelial progenitor cells (EPC), embryonic stem cells (ESC) and haematopoietic stem cells (HSC)) may play a pivotal role on the maintenance and regeneration of cardiovascular tissue. Age-associated changes of such cells may enhance the risk of developing CVD. The purpose of this review is to illustrate how cellular senescence may affect tissue repair and maintenance toward CVD, focusing on the role played by telomere length and microRNA expression. Finally, interventions aimed at improving the age-related decline in vascular cells during aging and disease, as well as strategies to harness the regenerative capacity of stem cells in CVD will be discussed.