A review of the pathophysiological mechanisms of doxorubicin-induced cardiotoxicity and aging explores how doxorubicin, a common chemotherapy drug, causes cardiac dysfunction and an accelerated aging phenotype. The study highlights that doxorubicin-induced cardiotoxicity (DCT) is linked to cellular senescence, DNA damage, telomere shortening, and oxidative stress, leading to a phenotype similar to aging. The mechanisms include DNA damage, mitochondrial dysfunction, calcium dysregulation, and increased reactive oxygen species (ROS). These processes are exacerbated by doxorubicin's interaction with DNA and its effect on topoisomerase IIb, leading to DNA breaks and mutations. The study also discusses the similarities between the aged heart and the doxorubicin-treated heart, including hypertrophy, fibrosis, and impaired diastolic function. Cellular senescence is a key factor in the accelerated aging phenotype, with senescent cells contributing to inflammation and tissue damage. The review also covers the role of epigenetic changes, such as DNA methylation and histone modifications, in the aging process and DCT. Mitochondrial dysfunction and mtDNA damage further contribute to the cardiotoxic effects of doxorubicin. The study emphasizes the importance of understanding these mechanisms to develop effective treatments for DCT and to improve the long-term survival of cancer survivors. Potential therapeutic strategies include senolytics and senomorphics, which target senescent cells and reduce their harmful effects. The review concludes that doxorubicin treatment leads to an accelerated aging phenotype, and further research is needed to develop cardioprotective strategies that can mitigate the long-term effects of this chemotherapy drug.A review of the pathophysiological mechanisms of doxorubicin-induced cardiotoxicity and aging explores how doxorubicin, a common chemotherapy drug, causes cardiac dysfunction and an accelerated aging phenotype. The study highlights that doxorubicin-induced cardiotoxicity (DCT) is linked to cellular senescence, DNA damage, telomere shortening, and oxidative stress, leading to a phenotype similar to aging. The mechanisms include DNA damage, mitochondrial dysfunction, calcium dysregulation, and increased reactive oxygen species (ROS). These processes are exacerbated by doxorubicin's interaction with DNA and its effect on topoisomerase IIb, leading to DNA breaks and mutations. The study also discusses the similarities between the aged heart and the doxorubicin-treated heart, including hypertrophy, fibrosis, and impaired diastolic function. Cellular senescence is a key factor in the accelerated aging phenotype, with senescent cells contributing to inflammation and tissue damage. The review also covers the role of epigenetic changes, such as DNA methylation and histone modifications, in the aging process and DCT. Mitochondrial dysfunction and mtDNA damage further contribute to the cardiotoxic effects of doxorubicin. The study emphasizes the importance of understanding these mechanisms to develop effective treatments for DCT and to improve the long-term survival of cancer survivors. Potential therapeutic strategies include senolytics and senomorphics, which target senescent cells and reduce their harmful effects. The review concludes that doxorubicin treatment leads to an accelerated aging phenotype, and further research is needed to develop cardioprotective strategies that can mitigate the long-term effects of this chemotherapy drug.