🔹Vascular Aging and Cardiovascular Diseases:
Aging leads to significant arterial changes, including increased arterial stiffness and endothelial dysfunction, which are strong predictors of cardiovascular disease (CVD) in older adults.
🔹Role of Cellular Senescence:
Senescent cells lose their ability to divide but remain metabolically active. They secrete inflammatory factors known as senescence-associated secretory phenotype (SASP), which contribute to chronic inflammation, oxidative stress, and the progression of age-related cardiovascular diseases.
🔹Mitochondrial Dysfunction in Senescence:
Mitochondrial dysfunction, characterized by increased production of reactive oxygen species (ROS), plays a critical role in cellular aging and vascular dysfunction. Interventions targeting mitochondrial ROS have shown potential in delaying senescence and improving cardiovascular health.
🔹Impact on Various Cell Types:
Cellular senescence affects multiple cell types within the cardiovascular system, including endothelial cells, vascular smooth muscle cells, and immune cells.
🔹Senolytics as a Therapeutic Strategy:
🔸 Dasatinib (D) and quercetin (Q) are among the first senolytics tested, showing effectiveness in inducing apoptosis in senescent cells in both animal models and human cell studies. This combination improves vascular function, reduces inflammation, and shows potential for treating age-related diseases.
🔸 The BCL-2 family of proteins is another target for senolytics. Drugs like ABT263 (Navitoclax) specifically induce apoptosis in senescent cells by inhibiting anti-apoptotic pathways, which has shown benefits in reducing arterial stiffness and improving endothelial function in aged mice.
🔸Ferroptosis, a form of regulated cell death dependent on iron and lipid peroxidation, has emerged as a potential mechanism for selectively targeting senescent cells. Studies have shown that senescent cells are more susceptible to ferroptosis, suggesting that drugs exploiting this pathway could effectively clear these cells and improve vascular health.
🔸 Recent research has identified cardiac glycosides, such as digoxin and ouabain, as potential senolytic agents. These drugs work by inhibiting Na+, K+ ATPase, leading to selective senolysis of senescent cells. However, their long-term effects and safety need further evaluation.
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