Telomeres as hallmarks of iPSC aging: A review on telomere dynamics during stemness and cellular reprogramming

Telomeres, the protective ends of chromosome, are key to tissue repair and regeneration. Telomere shortening is linked to aging and age-related disorders, while excessive telomerase activity may support tissue regeneration or transformation. Some of the functions of telomeres and telomerase may be mediated by its important role in the process of stemness. Active telomerase, and subsequent telomerase-dependent telomere extension, supports stem-cells self-renewal and pluripotency - essential for tissue healing. During cellular reprogramming, differentiated cells are converted into induced pluripotent stem cells (iPSCs), which resemble embryonic stem cells. During iPSC derivation, telomere length is reset, enhancing iPSCs’ regenerative potential. During this process, incomplete telomerase activation and telomere extension can lead to genomic instability and/or haltered cell functionality. Understanding the intricate relation of telomeres, telomerase and stemness may be critical when designing novel cell-based therapies targeting degenerative diseases or to unlock strategies to delay aging. Here, we explore the recent bibliography linking these areas, raising awareness of their important when designing novel breakthroughs in health and longevity.