A Review of Telomere Attrition in Cancer and Aging: Current Molecular Insights and Future Therapeutic Approaches
Mina Iskandar, M. Barbéro, Mohammed Tariq Jaber, Roy Chen, Romulo Gomez-Guevara, Edwin Cruz, Sandy D. Westerheide
Abstract
BACKGROUND/OBJECTIVES: As cells divide, telomeres shorten through a phenomenon known as telomere attrition, which leads to unavoidable senescence of cells. Unprotected DNA exponentially increases the odds of mutations, which can evolve into premature aging disorders and tumorigenesis. There has been growing academic and clinical interest in exploring this duality and developing optimal therapeutic strategies to combat telomere attrition in aging and cellular immortality in cancer. The purpose of this review is to provide an updated overview of telomere biology and therapeutic tactics to address aging and cancer. METHODS: We used the Rayyan platform to review the PubMed database and examined the ClinicalTrial.gov registry to gain insight into clinical trials and their results. RESULTS: Cancer cells activate telomerase or utilize alternative lengthening of telomeres to escape telomere shortening, leading to near immortality. Contrarily, normal cells experience telomeric erosion, contributing to premature aging disorders, such as Werner syndrome and Hutchinson-Gilford Progeria, and (2) aging-related diseases, such as neurodegenerative and cardiovascular diseases. CONCLUSIONS: The literature presents several promising therapeutic approaches to potentially balance telomere maintenance in aging and shortening in cancer. This review highlights gaps in knowledge and points to the potential of these optimal interventions in preclinical and clinical studies to inform future research in cancer and aging.