Reviewing the Role of Cellular Senescence in Cardiovascular Disease

Senescent cells are created and destroyed constantly in the body, but their numbers accumulate with age, an imbalance that is a consequence of raised rates of creation due to an age-damaged environment, and the failure of the immune system to rapidly clear these errant cells. Senescent cells actively secrete a pro-inflammatory, pro-growth mix of signals, useful in the short term in contexts such as suppression of precancerous lesions and coordination of wound healing. When present for the long term, senescent cell signaling is very harmful to cell and tissue function, however. It is an important contributing cause of chronic inflammation and many age-related conditions.

Cellular senescence is a state of stable cell-cycle arrest despite continued metabolic activity, which usually occurs in response to many endogenous and exogenous stresses during aging processes. Historically, senescence was first identified half a century ago, with the discovery that human diploid fibroblasts displayed a finite capacity for cell division because of telomere shortening (replicative senescence). Conversely, the telomere length-independent senescence was then observed in many aged or damaged tissues. Such stress-induced premature senescence (SIPS) can be triggered by distinctive stressful stimuli, including persistent DNA damage, oncogene activation, oxidative stress, and mitochondrial dysfunction in the cardiovascular system.

Eminently characterized by a proliferation arrest, the senescent cells are differed from other non-dividing cells (such as quiescent cells) with specific morphological and functional features. Growing evidences demonstrated that the senescent cardiovascular cells, including endothelial cells, vascular smooth muscle cells, fibroblast cells, cardiomyocytes, T cells and et al., were accumulated in the culprit lesions of cardiovascular system and act to improve or exacerbate the onset and outcome of cardiovascular diseases. While cellular senescence imposes an important role in suppressing tumorigenesis. There is strong evidence that cellular senescence also participates in the progression of heart regeneration, cardiac remodeling, atherosclerosis, and heart failure.

In this review, we first discuss the mechanisms and the features underlying cellular senescence. Then, we summarize the different types of senescent cells that present in cardiovascular systems and describe the pathophysiological implications of cellular senescence in cardiovascular disease. Moreover, we highlight the role of SIRT1 and mTOR in regulating senescence during age-related cardiovascular diseases. Finally, we focus on the emerging pro-senescent and anti-senescent therapies and discuss their therapeutic potential for cardiovascular diseases.


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