<p>Cardiovascular diseases (CVDs) pose a significant health challenge, particularly among aging populations. Age-related cellular transformations, such as apoptosis, fibrosis, and senescence, contribute to CVDs, necessitating a deeper understanding of cellular aging mechanisms. While animal models offer insights, their translational relevance remains limited, underscoring the need for human-based models. Induced pluripotent stem cells (iPSCs) present a promising avenue for aged tissue modeling, that enable personalized and ethical approaches. By differentiating iPSCs into induced cardiomyocytes (iCMs) and aging them, researchers can simulate age-related cardiac conditions. We assessed in vitro aging conditions by inducing oxidative stress, a key driver of aging, as it is crucial for replicating age-related pathological changes in aged tissue models. We exposed the iCMs to varying concentrations and exposure durations of hydrogen peroxide treatments. Through analyzing cellular aging markers such as senescence, p21 expression, and cellular waste accumulation, we compared the different treatments to determine the most time efficient approach. Our results showed that 7-day 200 µM hydrogen peroxide treatment leads to a significant increase in senescence, p21 and p16<sup>INK4A</sup> expression, and cellular waste accumulation, without inducing apoptosis. These cells can be used for developing iPSC-based aged tissue models towards advancing our understanding and treatment of age-related CVDs.</p>

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Inducing Oxidative Stress-Driven Senescent Phenotype in Induced Pluripotent Stem Cell Derived Cardiomyocytes

  • Hatice Emanet,
  • Frances DiPietro,
  • Sneha Philip,
  • Aylin Acun

摘要

Cardiovascular diseases (CVDs) pose a significant health challenge, particularly among aging populations. Age-related cellular transformations, such as apoptosis, fibrosis, and senescence, contribute to CVDs, necessitating a deeper understanding of cellular aging mechanisms. While animal models offer insights, their translational relevance remains limited, underscoring the need for human-based models. Induced pluripotent stem cells (iPSCs) present a promising avenue for aged tissue modeling, that enable personalized and ethical approaches. By differentiating iPSCs into induced cardiomyocytes (iCMs) and aging them, researchers can simulate age-related cardiac conditions. We assessed in vitro aging conditions by inducing oxidative stress, a key driver of aging, as it is crucial for replicating age-related pathological changes in aged tissue models. We exposed the iCMs to varying concentrations and exposure durations of hydrogen peroxide treatments. Through analyzing cellular aging markers such as senescence, p21 expression, and cellular waste accumulation, we compared the different treatments to determine the most time efficient approach. Our results showed that 7-day 200 µM hydrogen peroxide treatment leads to a significant increase in senescence, p21 and p16INK4A expression, and cellular waste accumulation, without inducing apoptosis. These cells can be used for developing iPSC-based aged tissue models towards advancing our understanding and treatment of age-related CVDs.