Targeting senescent cells for vascular aging and related diseases

Cardiovascular diseases are a serious threat to human health, especially in the elderly. Vascular aging makes people more susceptible to cardiovascular diseases due to significant dysfunction or senescence of vascular cells and maladaptation of vascular structure and function; moreover, vascular aging is currently viewed as a modifiable cardiovascular risk factor. To emphasize the relationship between senescent cells and vascular aging, we first summarize the roles of senescent vascular cells (endothelial cells, smooth muscle cells and immune cells) in the vascular aging process and inducers that contribute to cellular senescence. Then, we present potential strategies for directly targeting senescent cells (senotherapy) or preventively targeting senescence inducers (senoprevention) to delay vascular aging and the development of age-related vascular diseases. Finally, based on recent research, we note some important questions that still need to be addressed in the future. The relationships among cellular senescence inducers, senescent cells and vascular aging. Telomere-dependent replicative senescence and stress-induced premature senescence have different senescence inducers. These inducers comprise a complicated network and promote cell senescence in aortas. Senescent vascular cells lead to typical pathological changes of vascular aging by abnormal function and molecular expression, which further contribute to related vascular diseases. Cell senescence and other pathological changes induced the abnormalities in vascular structure and function, which are direct manifestations of vascular aging and related diseases. More details are provided in the main text. Abbreviation: ECs: Endothelium cells; ECM: Extracellular matrix; IIS: Impaired immunosurveillance; RAAS: Renin-angiotensin-aldosterone system; SASP: Senescence associated secretory phenotype; VSMCs: Vascular smooth muscle cells. [Display omitted] •Vascular aging is currently viewed as a modifiable cardiovascular risk factor.•Vascular cells senescence contributes to the progression of vascular aging along with age-related disorders.•The clearance of senescent cells by senotherapy or senoprevention is a candidate intervention to decelerate vascular aging.