Turkish Journal of Clinical Research · May 31, 2026
The telomere paradox: Dual regulatory roles in aging and cancer
By Altuğ T, Bayıroğlu F
Aging and cancer are biologically interconnected processes shaped by genomic stability and cellular replicative capacity. Telomere dynamics occupy a central position at the intersection of these conditions. Progressive telomere shortening, driven by cell division and oxidative stress, activates a DNA damage response that induces replicative senescence or apoptosis once a critical threshold is reached. While this mechanism contributes to age-related tissue decline, it simultaneously functions as a tumor-suppressive barrier by limiting uncontrolled proliferation. However, in the presence of defective cell-cycle checkpoints, telomere dysfunction promotes chromosomal instability and malignant transformation. In contrast to telomere attrition, telomerase reactivation stabilizes chromosome ends and restores sustained proliferative capacity, thereby enabling replicative immortality—a defining hallmark of cancer. Although telomerase activity may theoretically support regenerative potential, it also facilitates tumor progression. Together, these context-dependent effects define the “telomere paradox,” emphasizing the non-linear relationship between telomere length, telomerase activity, aging phenotypes, and cancer risk. This review integrates current knowledge on telomere structure, telomerase regulation, and shelterin-mediated protection within a conceptual framework linking telomere dynamics to both degenerative aging and oncogenic processes