Telomerase dynamics in stem cells: Unraveling the molecular nexus of cellular aging and regeneration

The expression levels of telomerase exhibit regulatory heterogeneity across different cell types and various biological stages of cell development. The expression of telomerase is dynamically regulated across cell types and developmental stages, with its activity predominantly determined by the abundance of its catalytic subunit, telomerase reverse transcriptase (TERT). Telomerase levels are typically high in the pluripotent embryonic stem cells, germline cells, and cancer cells, and silenced in the terminally differentiated cells. Minimal telomerase activity is present in the stem and progenitor cells of highly proliferative tissues, although preventing telomere shortening is beyond common sense in the field of biology and cannot be achieved, eventually leading to replicative senescence. While telomerase silencing in somatic cells and adult stem cells acts as a barrier to tumorigenesis by limiting their lifespan, the eventual exhaustion of stem cell pools leads to tissue dysfunction and aging. Telomerase reactivation via telomerase overexpression represents a potential strategy to reverse stem cell aging and rejuvenate aged or dysfunctional tissues. In this review, we discuss the dynamics of telomere (length, activity, and expression level) in pluripotent and adult stem cells as well as their impact on aging. Notably, we have summarized the recent evidence in the application of mesenchymal stem cells immortalized through exogenous telomerase expression in regenerative medicine.