Premature Senescence and Cardiovascular Disease Following Cancer Treatments: Mitochondria-Mediated Mechanistic Insights
- 1Department of Cosmeceutics, College of Pharmacy, China Medical University, Shui-Nan Campus, No. 100, Sec.1 Jingmao Road, Beitun District, Taichung 406040, Taiwan
Abstract
The remarkable enhancement in cancer survival attained over recent decades has shifted attention toward the long-term cardiovascular effects of anticancer therapies. Beyond overt cardiotoxicity, accumulating evidence indicates that many conventional chemotherapeutics, including radiotherapy, targeted agents, and emerging immunotherapies, accelerate biological aging of the cardiovascular system through the induction of premature cellular senescence. Senescent endothelial cells, cardiomyocytes, vascular smooth muscle cells, cardiac fibroblasts, and resident immune cells exhibit persistent growth arrest accompanied by metabolic reprogramming, chronic inflammation, mitochondrial dysfunction, and acquisition of a senescence-associated secretory phenotype (SASP), collectively contributing to adverse cardiac remodeling, vascular dysfunction, myocardial fibrosis, and accelerated atherosclerosis. Among the interconnected mechanisms driving therapy-induced senescence, mitochondria have emerged as central regulators integrating oxidative stress, DNA damage responses, bioenergetic alterations, impaired mitophagy, mitochondrial dynamics, calcium dysregulation, and innate immune activation. Through the production of reactive oxygen species (ROS), chronic inflammatory signaling, the release of mitochondrial DNA, and the activation of inflammasomes, dysfunctional mitochondria actively amplify senescence rather than acting only as organelles that produce energy. This creates self-sustaining feed-forward loops that promote cardiovascular aging long after cancer treatment is completed. This review critically examines the molecular mechanisms linking anticancer therapies to premature cardiovascular senescence with particular emphasis on mitochondria-centered signaling networks. I address therapy-specific mitochondrial alterations induced by HER2-targeted treatments, immune checkpoint inhibitors, ionizing radiation, platinum-based drugs, anthracyclines, and more recent anticancer modalities, emphasizing interconnected pathways despite disparate fundamental mechanisms of action. Emerging biomarkers of mitochondrial dysfunction and senescence, together with therapeutic prospects involving senolytics, senomorphics, mitochondria-targeted antioxidants, metabolic modulators, and interventions reestablishing mitochondrial quality control, are also evaluated. Finally, I identify unresolved questions limiting clinical translation and propose future research directions aimed at preserving cardiovascular health in the rapidly expanding population of cancer survivors.
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BibTeX
@article{pandey2026premature,
title = {{Premature Senescence and Cardiovascular Disease Following Cancer Treatments: Mitochondria-Mediated Mechanistic Insights}},
author = {Sudhir Pandey},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms272110011},
url = {https://www.mdpi.com/1422-0067/27/21/10011},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Premature Senescence and Cardiovascular Disease Following Cancer Treatments: Mitochondria-Mediated Mechanistic Insights
AU - Sudhir Pandey
PY - 2026
DA - 2026/11/08
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms272110011
UR - https://www.mdpi.com/1422-0067/27/21/10011
AB - The remarkable enhancement in cancer survival attained over recent decades has shifted attention toward the long-term cardiovascular effects of anticancer therapies. Beyond overt cardiotoxicity, accumulating evidence indicates that many conventional chemotherapeutics, including radiotherapy, targeted agents, and emerging immunotherapies, accelerate biological aging of the cardiovascular system through the induction of premature cellular senescence. Senescent endothelial cells, cardiomyocytes, vascular smooth muscle cells, cardiac fibroblasts, and resident immune cells exhibit persistent growth arrest accompanied by metabolic reprogramming, chronic inflammation, mitochondrial dysfunction, and acquisition of a senescence-associated secretory phenotype (SASP), collectively contributing to adverse cardiac remodeling, vascular dysfunction, myocardial fibrosis, and accelerated atherosclerosis. Among the interconnected mechanisms driving therapy-induced senescence, mitochondria have emerged as central regulators integrating oxidative stress, DNA damage responses, bioenergetic alterations, impaired mitophagy, mitochondrial dynamics, calcium dysregulation, and innate immune activation. Through the production of reactive oxygen species (ROS), chronic inflammatory signaling, the release of mitochondrial DNA, and the activation of inflammasomes, dysfunctional mitochondria actively amplify senescence rather than acting only as organelles that produce energy. This creates self-sustaining feed-forward loops that promote cardiovascular aging long after cancer treatment is completed. This review critically examines the molecular mechanisms linking anticancer therapies to premature cardiovascular senescence with particular emphasis on mitochondria-centered signaling networks. I address therapy-specific mitochondrial alterations induced by HER2-targeted treatments, immune checkpoint inhibitors, ionizing radiation, platinum-based drugs, anthracyclines, and more recent anticancer modalities, emphasizing interconnected pathways despite disparate fundamental mechanisms of action. Emerging biomarkers of mitochondrial dysfunction and senescence, together with therapeutic prospects involving senolytics, senomorphics, mitochondria-targeted antioxidants, metabolic modulators, and interventions reestablishing mitochondrial quality control, are also evaluated. Finally, I identify unresolved questions limiting clinical translation and propose future research directions aimed at preserving cardiovascular health in the rapidly expanding population of cancer survivors.
SN - 1422-0067
ER -