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REVIEW ARTICLE

Senescence in cardiovascular diseases: Insights into metabolic dysfunction in vascular cells

Ying Qu1,2,3 ,  Anan Wang4 ,  Caihua Long4 ,  Qiuyue Gao1,2,3 ,  Baoqi Yu1,2,3*
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1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
2 The Key Laboratory of Cardiovascular Remodeling-Related Diseases, Ministry of Education, Beijing, China
3 Beijing Key Laboratory of Metabolic Disorder-Related Cardiovascular Diseases, Beijing, China
4 Department of Basic Medical Sciences, Capital Medical University, Beijing, China
Global Translational Medicine, 4619 https://doi.org/10.36922/gtm.4619
Submitted: 21 August 2024 | Accepted: 14 October 2024 | Published: 21 November 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Senescence is an independent risk factor and plays a critical role in altering vascular structure and functions. Reportedly, senescence accelerates pathological processes and notably increases the risk of cardiovascular diseases, such as atherosclerosis, which are the leading causes of mortality worldwide. Therefore, understanding vascular senescence mechanisms is essential for controlling the increasing incidence and mortality of cardiovascular diseases. This review highlights the progress in research on the various mechanisms underlying the senescence of endothelial cells, smooth muscle cells, and macrophages – such as stem cell senescence, metabolic dysregulation, mitochondrial autophagy (mitophagy) impairment, and ferroptosis – and summarizes various antisenescence strategies to target these mechanisms. Key interventions include restoration of the nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide (NAD+/NADH) ratio and administration of metformin and acarbose to regulate blood glucose levels, which balances the cellular energy and redox. Further, stem cell therapies, rapamycin administration, and melatonin supplementation demonstrate substantial potential. In addition, exercise, dietary modification, and caloric restriction support senescence mitigation. These strategies illustrate the multifaceted nature of senescence and highlight the potential of integrated therapeutic approaches to extend the health span and delay age-related diseases. This review provides a comprehensive summary of age-related metabolic pathways and explores promising antisenescence therapeutic strategies, thereby providing valuable insights into the prevention, diagnosis, and treatment of senescence-related vascular diseases.

Keywords
Senescence
Cardiovascular disease
Vascular disease
Metabolism
Stem cells
Funding
This work was supported by a grant from the National Key Research and Development Program of China (2023YFC3606500) and the National Natural Science Foundation of China (32271231).
Conflict of interest
Baoqi Yu is an Editorial Board Member of this journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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