Senescent Cells: A Therapeutic Target in Cardiovascular Diseases
Masayoshi Suda,
Karl H. Paul,
Tohru Minamino,
Jordan D. Miller,
Amir Lerman,
Georgina M. Ellison-Hughes,
Tamar Tchkonia,
James L. Kirkland
Affiliations
Masayoshi Suda
Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First St., S.W., Rochester, MN 55905, USA
Karl H. Paul
Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First St., S.W., Rochester, MN 55905, USA
Tohru Minamino
Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Jordan D. Miller
Division of Cardiovascular Surgery, Mayo Clinic College of Medicine, 200 First St., S.W., Rochester, MN 55905, USA
Amir Lerman
Department of Cardiovascular Medicine, Mayo Clinic, 200 First St., S.W., Rochester, MN 55905, USA
Georgina M. Ellison-Hughes
Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, Guy’s Campus, King’s College London, London SE1 1UL, UK
Tamar Tchkonia
Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First St., S.W., Rochester, MN 55905, USA
James L. Kirkland
Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First St., S.W., Rochester, MN 55905, USA
Senescent cell accumulation has been observed in age-associated diseases including cardiovascular diseases. Senescent cells lack proliferative capacity and secrete senescence-associated secretory phenotype (SASP) factors that may cause or worsen many cardiovascular diseases. Therapies targeting senescent cells, especially senolytic drugs that selectively induce senescent cell removal, have been shown to delay, prevent, alleviate, or treat multiple age-associated diseases in preclinical models. Some senolytic clinical trials have already been completed or are underway for a number of diseases and geriatric syndromes. Understanding how cellular senescence affects the various cell types in the cardiovascular system, such as endothelial cells, vascular smooth muscle cells, fibroblasts, immune cells, progenitor cells, and cardiomyocytes, is important to facilitate translation of senotherapeutics into clinical interventions. This review highlights: (1) the characteristics of senescent cells and their involvement in cardiovascular diseases, focusing on the aforementioned cardiovascular cell types, (2) evidence about senolytic drugs and other senotherapeutics, and (3) the future path and clinical potential of senotherapeutics for cardiovascular diseases.
