Student and Faculty Publications
Publication Date
12-6-2022
Journal
Biology
Abstract
Despite progress in biomedical technologies, cardiovascular disease remains the main cause of mortality. This is at least in part because current clinical interventions do not adequately take into account aging as a driver and are hence aimed at suboptimal targets. To achieve progress, consideration needs to be given to the role of cell aging in disease pathogenesis. We propose a model unifying the fundamental processes underlying most age-associated cardiovascular pathologies. According to this model, cell aging, leading to cell senescence, is responsible for tissue changes leading to age-related cardiovascular disease. This process, occurring due to telomerase inactivation and telomere attrition, affects all components of the cardiovascular system, including cardiomyocytes, vascular endothelial cells, smooth muscle cells, cardiac fibroblasts, and immune cells. The unified model offers insights into the relationship between upstream risk factors and downstream clinical outcomes and explains why interventions aimed at either of these components have limited success. Potential therapeutic approaches are considered based on this model. Because telomerase activity can prevent and reverse cell senescence, telomerase gene therapy is discussed as a promising intervention. Telomerase gene therapy and similar systems interventions based on the unified model are expected to be transformational in cardiovascular medicine.
Keywords
cell senescence, aging, cardiovascular disease, telomere, telomerase, gene therapy, senolytics, autophagy, senotherapeutics
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Cardiology Commons, Cardiovascular Diseases Commons, Critical Care Commons, Medical Sciences Commons, Oncology Commons
Comments
Data Availability Statement
PMID: 36552277