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11
Feb
TERT Biology: Telomerase Function, Genomic Stability, and Aging
Exploring the molecular guardian of the eukaryotic genome and its implications for human longevity.
Telomerase reverse transcriptase (TERT) is the catalytic subunit of the telomerase holoenzyme complex. As the primary engine for maintaining telomere length, TERT plays a decisive role in cellular immortality, genomic integrity, and the biological clock of aging.
I. Molecular Structure & Activity
TERT functions as the enzymatic core of the telomerase ribonucleoprotein complex. To function, it requires a coordinated assembly:
- TERT Protein: The catalytic engine providing reverse transcriptase activity.
- TERC (RNA Component): The intrinsic template for telomere extension.
- Accessory Proteins: Regulators for assembly and nuclear localization.
II. Telomere Length Maintenance
By adding nucleotide repeats (TTAGGG) to the 3′ ends of chromosomes, TERT compensates for the "end-replication problem." This activity is a hallmark of high-turnover cell populations:
Stem Cells Sustained self-renewal
Germline Genetic continuity
Immune Cells Rapid expansion capacity
III. Genome Stability & Senescence
Critically short telomeres trigger a DNA damage response that leads to replicative senescence. TERT-mediated stabilization prevents:
- Chromosomal end-to-end fusion
- Mitotic catastrophe
- Genomic rearrangements
- Apoptosis activation
IV. TERT Reactivation in Tumorigenesis
Approximately 85–90% of human malignancies exploit TERT reactivation to achieve immortality. This allows cancer cells to bypass the natural hayflick limit and maintain unlimited proliferative potential. Common TERT promoter mutations are key drivers in melanoma, glioblastoma, and bladder cancer.
V. TERT in Aging-Associated Diseases
| System | Pathological Implication |
|---|---|
| Cardiovascular | Endothelial dysfunction and atherosclerosis. |
| Neurological | Increased vulnerability to neurodegenerative decline. |
| Immune | Immunosenescence and reduced vaccine efficacy. |
VI. Non-Canonical Functions & Future Research
Beyond the telomere, emerging research highlights TERT's "moonlighting" roles:
- Mitochondrial Protection: Protecting mtDNA from oxidative stress.
- Transcriptional Regulation: Interacting with the Wnt/β-catenin pathway.
- Therapeutic Targets: Developing small-molecule inhibitors for oncology and mRNA-based activators for regenerative medicine.
Biofargo team
