Journal Article Review Ahead of print
PubMed: 41935581 DOI: 10.1016/j.arr.2026.103119
Endothelial Cell Senescence and Mitochondrial Dysfunction in Vascular Ageing.
Ageing Res Rev
Authors: Iga Walczak, Maria Tarnawska, Klaudia Stawarska, Alicja Braczko, Aleksandra Paterek, Filip Rolski, Przemysław Leszek, Dorota Smolarek, Małgorzata Kapusta, Magdalena Narajczyk, Jean-Luc Cracowski, Beata Schlichtholz, Marcin Hellmann, Michał Mączewski, Barbara Kutryb-Zając
Affiliations
- Department of Biochemistry, Medical University of Gdansk, Dębinki 1, 80-211 Gdańsk, Poland.
- Department of Cardiac Diagnostics, Medical University of Gdansk, Smoluchowskiego 17, 80-214 Gdańsk, Poland.
- Department of Clinical Physiology, The Centre of Postgraduate Medical Education, Marymoncka 99, 01-813 Warsaw, Poland.
- Heart Failure, Transplantology and Mechanical Circulatory Support Department, National Institute of Cardiology, Alpejska 42, 04-628 Warsaw, Poland.
- Bioimaging Laboratory, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.
- Department of Pharmacology, INSERM, U1300, HP2, Grenoble-Alpes University, Grenoble, France.
- Department of Cardiac Diagnostics, Medical University of Gdansk, Smoluchowskiego 17, 80-214 Gdańsk, Poland.
- Department of Clinical Physiology, The Centre of Postgraduate Medical Education, Marymoncka 99, 01-813 Warsaw, Poland.
- Department of Biochemistry, Medical University of Gdansk, Dębinki 1, 80-211 Gdańsk, Poland; Centre of Experimental Cardiooncology, Medical University of Gdansk, Smoluchowskiego 17, 80-214 Gdańsk, Poland.
Abstract
The vascular endothelium performs numerous regulatory functions that impact inflammatory responses, thrombosis, vascular tone and angiogenesis. Endothelial dysfunction is a key contributor to the pathogenesis of various human diseases, either as a primary trigger or as a consequence of organ damage. This review examines how ageing reshapes endothelial cell metabolism and mitochondrial function, progressively undermining endothelial homeostasis and resilience. Age-related endothelial alterations, including reduced nitric oxide bioavailability, heightened oxidative stress, impaired vasodilatory capacity and pro-inflammatory activation, arise from coordinated shifts in energy production, substrate utilization and redox signaling. In this context, cellular senescence, a stable arrest of the cell cycle accompanied by distinct metabolic, secretory and inflammatory changes, appears to be an important response to cumulative metabolic and mitochondrial stress. Senescent endothelial cells not only reflect this stress burden but also actively propagate dysfunction through sustained pro-inflammatory and pro-oxidant signalling, thereby accelerating vascular ageing. We highlight the central role of mitochondria in these events. Age-associated mitochondrial dysfunction disrupts bioenergetics, enhances reactive oxygen species generation and fuels chronic low-grade inflammation, amplifying endothelial decline. By bringing together current evidence-based knowledge on endothelial cell bioenergetics, mitochondrial impairment and metabolic reprogramming, this review identifies mitochondria-driven metabolic deterioration as a key mechanism underlying endothelial ageing and underscores mitochondrial metabolism as a promising, yet underexploited, therapeutic target in age-related vascular dysfunction.
MeSH
Cells, Aging, Stress, Physiological, Cellular Senescence, Mitochondria, Endothelial Cells, Endothelium