Senescent cells: a therapeutic target for cardiovascular disease

Abstract

Cellular senescence, a major tumor-suppressive cell fate, has emerged from humble beginnings as an in vitro phenomenon into recognition as a fundamental mechanism of aging. In the process, senescent cells have attracted attention as a therapeutic target for age-related diseases, including cardiovascular disease (CVD), the leading cause of morbidity and mortality in the elderly. Given the aging global population and the inadequacy of current medical management, attenuating the health care burden of CVD would be transformative to clinical practice. Here, we review the evidence that cellular senescence drives CVD in a bimodal fashion by both priming the aged cardiovascular system for disease and driving established disease forward. Hence, the growing field of senotherapy (neutralizing senescent cells for therapeutic benefit) is poised to contribute to both prevention and treatment of CVD.

Aged‐senescent cells contribute to impaired heart regeneration

“…Senescent cells have emerged as bona fide drivers of aging and age‐related CVD, which suggests strategies aimed at reducing or eliminating senescent cells could be a viable target to treat and prevent CVD (Childs, Li, & Deursen, ). In 18‐month‐old INK‐ATTAC mice, p16 INK4a ‐positive cells contribute to cardiac aging and these senescent cells decreased following AP20187‐treatment (Baker et al, ).…”

Concise Review: The Endothelial Cell Extracellular Matrix Regulates Tissue Homeostasis and Repair

“…The term matricellular has been applied to this group of extracellular proteins that do not contribute directly to the formation of structural ECM elements but serve to modulate cell–matrix interactions and cell function. While they usually have limited expression in adult life, they can become upregulated and released from the ECM during injury and repair . The production and release of matricellular proteins upon injury allows for binding of these proteins to a variety of receptors, growth factors and proteases in the capillary pericellular space, generally reducing cell adhesion and proliferation, and thus tuning ECM remodeling down (Fig.…”

The angiotensin‐(1‐7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation

“…The SASP is considered a main driver of sterile age‐related inflammation which favors leukocyte recruitment and predisposes to vascular disease (Donato et al, ; Tchkonia, Zhu, Deursen, Campisi, & Kirkland, ). In this context, the search of therapeutic tools to attenuate premature endothelial senescence arises as a promising strategy to attenuate vascular aging and its complications (Childs, Li, & Deursen, ).…”