Senescent Cells: A Therapeutic Target in Cardiovascular Diseases

Author:

Suda Masayoshi12ORCID,Paul Karl H.13ORCID,Minamino Tohru24,Miller Jordan D.5,Lerman Amir6,Ellison-Hughes Georgina M.78ORCID,Tchkonia Tamar1,Kirkland James L.19

Affiliation:

1. Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First St., S.W., Rochester, MN 55905, USA

2. Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan

3. Department of Physiology and Pharmacology, Karolinska Institutet, Solnavägen 9, 171 65 Solna, Sweden

4. Japan Agency for Medical Research and Development-Core Research for Evolutionary Medical Science and Technology (AMED-CREST), Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan

5. Division of Cardiovascular Surgery, Mayo Clinic College of Medicine, 200 First St., S.W., Rochester, MN 55905, USA

6. Department of Cardiovascular Medicine, Mayo Clinic, 200 First St., S.W., Rochester, MN 55905, USA

7. 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

8. Centre for Stem Cells and Regenerative Medicine, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, Guy’s Campus, King’s College London, London SE1 1UL, UK

9. Division of General Internal Medicine, Department of Medicine, Mayo Clinic, 200 First St., S.W., Rochester, MN 55905, USA

Abstract

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.

Funder

US National Institutes of Health

a Grant-in-Aid for Scientific Research

Grant-in-Aid for Challenging Research

MEXT, AMED-CREST

the Moonshot Research and Development Program

Heart Research

King’s Together Fund Strategic Award, and ‘RENOIR’, the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie

Publisher

MDPI AG

Subject

General Medicine

Reference306 articles.

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