• Investigation of Cellular Aging Structures and Processes in the Progression of Endometriosis review article
  • Taban Razaghiyan,1 Saman Hakimian,2,*
    1. Taban Razaghiyan, Islamic Azad University Science and Research Branch
    2. Phd. student of Microbiology ,Biology department , Islamic Azad University Central Tehran Branch, Tehran , Iran


  • Introduction: Endometriosis is a chronic and often painful condition in which tissue similar to the endometrium grows outside the uterus. Studies have shown that a more detailed understanding of cellular aging processes and their effects could aid in preventing the acceleration and progression of endometriosis. By utilizing tools such as multi-omics datasets, the Summary-data-based Mendelian Randomization (SMR) method, and examining mechanisms including chromosome and telomere regulation, the Waddington epigenetic landscape model, and processes like telomere structure, it is possible to explore the link between endometriosis and cellular aging. These insights can be applied toward targeted therapies and serve as a bridge for future research.
  • Methods: Relationship Between Endometriosis, Chromosome/Telomere Regulation, and T-loop Formation. Endometrial cells undergo frequent divisions due to menstrual cycles and inflammation, which can lead to telomere shortening and trigger senescence or apoptosis. Environmental factors such as stress and oxidative damage can further accelerate telomere attrition. Additionally, defects in T-loop formation may lead to abnormal chromosome end-to-end fusions and genomic instability, thereby contributing to the progression of endometriosis.
  • Results: 1. Multi-omics Data and the SMR Method Using genes such as MAP3K5, THRB, and ENG, and applying the SMR method—which leverages genetic variants randomly assigned at conception (via tools such as pQTL, mQTL, and eQTL)—it is possible to investigate whether the expression of a target gene is influenced by DNA methylation at CpG sites. 2. Impact of Waddington’s Epigenetic Landscape on Cellular Aging. As cells age, they move further down the “landscape,” gradually becoming more differentiated. Additionally, epigenetic drift may occur, involving changes in DNA methylation patterns over time, along with histone modifications—such as hypermethylation of tumor suppressor gene promoters—which can contribute to cellular senescence and age-related diseases. Ultimately, the epigenetic noise theory of aging suggests that random molecular changes can divert cells toward undesirable fates (e.g., malignant transformation). These insights have driven interest in senolytic drugs, which selectively eliminate senescent cells.
  • Conclusion: Findings suggest that by using techniques such as SMR and multi-omics analysis, developing senolytic drugs inspired by the Waddington model, and preventing genomic instabilities like telomere shortening, it may be possible to halt the progression of endometriosis. However, discrepancies remain in the field of telomere shortening, which require further investigation and refinement in future research.
  • Keywords: SMR method- Waddington’s epigenetic landscape- chromosome and telomere regulation