ENGINEERING TELOMERE MAINTENANCE SYSTEMS FOR DELAYING CELLULAR SENESCENCE IN STEM CELLS

Abstract

Background: Cellular senescence is an important biological process associated with aging, depletion of stem cells and impaired tissue regeneration. Repeated cell division causes telomere shortening, which leads to genomic instability and loss of stem cell function. The emerging technologies of advanced telomere engineering have exhibited promise as therapeutic strategies to delay senescence and improve regenerative potential .

 Objective: The study aimed to assess engineered telomere maintenance systems to postpone cellular senescence in stem cells, employing genome engineering and telomerase activation methods.

Methodology: Human mesenchymal stem cells and induced pluripotent stem cells were used for experimental and computational analysis. A comparative evaluation of therapeutic strategies including activation of telomerase reverse transcriptase (TERT), CRISPR based telomere editing, epigenetic modification and rejuvenation of iPSC was made considering parameters such as telomere elongation, proliferation rate, reduction of oxidative stress and suppression of senescence markers.

Findings: TERT activation increased telomere length by 46% and reduced senescence associated β-galactosidase activity by 52%. iPSC rejuvenation showed the greatest mitochondrial recovery (58%) and reactive oxygen species reduction (53%). The CRISPR-based telomere editing caused a 44% increase in stem cell proliferation.

Conclusions: Engineered telomere maintenance systems are a promising therapeutic approach to slow down cellular senescence and to promote regenerative medicine strategies.