Senescence in cardiovascular diseases: Insights into metabolic dysfunction in vascular cells

Senescence is an independent risk factor and plays a critical role in altering vascular structure and functions. Reportedly, senescence accelerates pathological processes and notably increases the risk of cardiovascular diseases, such as atherosclerosis, which are the leading causes of mortality worldwide. Therefore, understanding vascular senescence mechanisms is essential for controlling the increasing incidence and mortality of cardiovascular diseases. This review highlights the progress in research on the various mechanisms underlying the senescence of endothelial cells, smooth muscle cells, and macrophages – such as stem cell senescence, metabolic dysregulation, mitochondrial autophagy (mitophagy) impairment, and ferroptosis – and summarizes various antisenescence strategies to target these mechanisms. Key interventions include restoration of the nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide (NAD+/NADH) ratio and administration of metformin and acarbose to regulate blood glucose levels, which balances the cellular energy and redox. Further, stem cell therapies, rapamycin administration, and melatonin supplementation demonstrate substantial potential. In addition, exercise, dietary modification, and caloric restriction support senescence mitigation. These strategies illustrate the multifaceted nature of senescence and highlight the potential of integrated therapeutic approaches to extend the health span and delay age-related diseases. This review provides a comprehensive summary of age-related metabolic pathways and explores promising antisenescence therapeutic strategies, thereby providing valuable insights into the prevention, diagnosis, and treatment of senescence-related vascular diseases.