Abstract
Aging is accompanied by a progressive decline of endothelial function and a progressive drift toward a systemic pro-inflammatory status that has been designated “inflammaging”. Both phenomena are accelerated and exacerbated in patients with the most common age-related diseases (ARDs), including cancer. The finding that chronic cell stress activates a pro-inflammatory program leading to acquisition of the senescence-associated secretory phenotype (SASP) and to the propagation of senescence to surrounding cells through the secretome, suggests that cell senescence may have a role in both processes. Here we: i) describe the role of cell senescence in endothelial dysfunction, ii) emphasize the contribution of the endothelial cell SASP to inflammaging, and iii) suggest that selective removal of senescent endothelial cells may not only hinder such harmful processes, but also reduce the risk of developing ARDs and their complications. Although in vivo detection and targeting of senescent endothelial cells are still being investigated, it is likely that therapeutic strategies based on antioxidant and anti-inflammatory compounds would involve generalized anti-aging effects also benefiting endothelial cells. MicroRNA (miRNAs) - single-stranded, non-coding RNAs expressed by all living cells and involved in the epigenetic modulation of all transcriptional programs - may constitute an innovative, valuable tool to detect and target senescent endothelial cells and to devise treatments that can slow down the pro-inflammatory program activated in senescent endothelial cells.
Keywords: Cancer, cell senescence, endothelial cells, endothelial dysfunction, inflammaging, microRNA, miR-126-3p, NFkB, senescence, senolytic compound, T2DM.
Graphical Abstract
60
7
1
1