Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation.

1st Department of Cardiology Hippokration Hospital Medical School National and Kapodistrian University of Athens Athens Greece

1st Department of Internal Medicine University Hospital Pavol Jozef Šafárik University of Košice Košice Slovakia

Biomedical Research Institute IDIBGI Girona Spain; Department of Pulmonary Medicine Hospital Clínic Institut d'Investigacions Biomèdiques August Pi i Sunyer de Enfermedades Respiratorias Madrid Spain

Cardiovascular Program ICCC Institut d'Investigació Biomèdica Sant Pau Instituto de Salud Carlos 3 Madrid Spain

Centre for Cardiovascular Health and Ageing Cardiff Metropolitan University Cardiff UK

CIBER de Diabetes y enfermedades Metabólicas asociadas Barcelona Spain

Department of Biomedical Engineering CARIM School for Cardiovascular Diseases Maastricht University the Netherlands; GROW School for Oncology and Reproduction Maastricht University the Netherlands

Department of Biomedical Engineering CARIM School for Cardiovascular Diseases Maastricht University the Netherlands; Macquarie Medical School Faculty of Medicine Health and Human Sciences Macquarie University Australia

Department of Biophysics School of Medicine Yeditepe University Istanbul Turkiye

Department of Cardiology Hospital of Ataturk Training and Research Hospital Katip Celebi University Izmir Turkiye

Department of Internal Medicine Division of Vascular Disease and Pharmacology Erasmus Medical Center Erasmus University Rotterdam the Netherlands

Department of Medical Biology School of Medicine Yeditepe University Istanbul Turkiye

Department of Medicine and Surgery University of Perugia Perugia Italy

Department of Molecular Biology and Genetics Faculty of Engineering and Natural Sciences Acibadem Mehmet Ali Aydinlar University Istanbul Turkiye

Department of Pharmacology Faculty of Medicine Dokuz Eylul University Izmir Turkiye

Department of Pharmacology Faculty of Pharmacy Ege University Izmir Turkiye

Department of Pharmacology Faculty of Pharmacy Ege University Izmir Turkiye; Department of Pharmacology Faculty of Pharmacy Acıbadem Mehmet Aydinlar University Istanbul Turkiye

Developmental Endocrinology Research Group University of Glasgow Glasgow UK

Institute of Enzymology Research Centre for Natural Sciences Budapest Hungary

Institute of Enzymology Research Centre for Natural Sciences Budapest Hungary; Department of Molecular Biology Semmelweis University Budapest Hungary

Laboratory of Pharmacology and Pharmaceutical Care Faculty of Pharmacy University of Coimbra Coimbra Portugal; Coimbra Institute for Clinical and Biomedical Research Faculty of Medicine University of Coimbra Coimbra Portugal; Center for Innovative Biomedicine and Biotechnology University of Coimbra Coimbra Portugal

Laboratory of Physiopharmacology University of Antwerp Antwerp Belgium

Lund University Department of Clinical Sciences Malmo Sweden

Molecular Cardiology Dept of Cardiology 1 Coronary and Peripheral Vascular Disease University Hospital Münster Westfälische Wilhelms Universität 48149 Münster Germany; Department of Medical Genetics 3rd Faculty of Medicine Charles University 100 00 Prague Czechia

School of Kinesiology University of Michigan Ann Arbor MI USA

School of Nursing Psychotherapy and Community Health Dublin City University Dublin Ireland

UMR CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire Reims France

UMR CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire Reims France; Laboratoire de Biochimie Pharmacologie Toxicologie Centre Hospitalier et Universitaire de Reims Reims France

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